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Cited by 309Diabetes Treatment and ManagementDiabetes, Cardiovascular Risks, and LipoproteinsCoronary Interventions and Diagnostics

Clinical management of stable coronary artery disease in patients with type 2 diabetes mellitus: a scientific statement from the American Heart Association

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Arnold, Suzanne V., Bhatt, Deepak L., Barsness, Gregory W., Beatty, Alexis L., Deedwania, Prakash C., Inzucchi, Silvio E., Kosiborod, Mikhail, Leiter, Lawrence A. +4 more·2020·Circulation
DOI 10.1161/cir.0000000000000766PMC PMC12204403
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Abstract

Although cardiologists have long treated patients with coronary artery disease (CAD) and concomitant type 2 diabetes mellitus (T2DM), T2DM has traditionally been considered just a comorbidity that affected the development and progression of the disease. Over the past decade, a number of factors have shifted that have forced the cardiology community to reconsider the role of T2DM in CAD. First, in addition to being associated with increased cardiovascular risk, T2DM has the potential to affect a number of treatment choices for CAD. In this document, we discuss the role that T2DM has in the selection of testing for CAD, in medical management (both secondary prevention strategies and treatment of stable angina), and in the selection of revascularization strategy. Second, although glycemic control has been recommended as a part of comprehensive risk factor management in patients with CAD, there is mounting evidence that the mechanism by which glucose is managed can have a substantial impact on cardiovascular outcomes. In this document, we discuss the role of glycemic management (both in intensity of control and choice of medications) in cardiovascular outcomes. It is becoming clear that the cardiologist needs both to consider T2DM in cardiovascular treatment decisions and potentially to help guide the selection of glucose-lowering medications. Our statement provides a comprehensive summary of effective, patient-centered management of CAD in patients with T2DM, with emphasis on the emerging evidence. Given the increasing prevalence of T2DM and the accumulating evidence of the need to consider T2DM in treatment decisions, this knowledge will become ever more important to optimize our patients’ cardiovascular outcomes.

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  • Premisecitation

    Many patients with type 2 diabetes and coronary disease, including after acute coronary syndrome, do not receive proven therapies such as high-intensity statins, dual antiplatelet therapy, ACE inhibitors or ARBs, and glucose-lowering drugs with cardiovascular benefit.

    “substantial proportions of patients with T2DM and CAD, including those after an acute coronary syndrome, do not receive therapies with proven cardiovascular benefit such as high-intensity statins, dual antiplatelet therapy, angiotensin converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs), and glucose-lowering agents with proven cardiovascular benefits.21”
    Quote in the paperSubstantial claim0 of 1 sources checked
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  • Premisecitation

    In CAPRIE, clopidogrel reduced ischemic events more than aspirin without excess bleeding among 19,185 patients with prior myocardial infarction, ischemic stroke, or peripheral artery disease.

    “In the CAPRIE trial (Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events), clopidogrel was superior to aspirin in reducing ischemic events with no excess of bleeding in 19 185 patients with prior myocardial infarction, ischemic stroke, or peripheral artery disease.47”
    Quote in the paperSubstantial claim0 of 1 sources checked
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  • Premisecitation

    Among 3,866 CAPRIE patients with diabetes, clopidogrel's advantage over aspirin was larger.

    “In the subset of 3866 patients with diabetes mellitus, the benefits of clopidogrel over aspirin were even greater.48”
    Quote in the paperSubstantial claim0 of 1 sources checked
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  • Premisecitation

    Type 2 diabetes is linked to a generalized prothrombotic state caused by altered coagulation and platelet function.

    “Among the factors contributing to an elevated cardiovascular risk in patients with T2DM is a generalized prothrombotic state23,24 attributable to altered coagulation and platelet function”
    Quote in the paperSubstantial claim0 of 2 sources checked
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  • Premisereasoning

    Type 2 diabetes can influence several decisions about how coronary artery disease is treated.

    “T2DM has the potential to affect a number of treatment choices for CAD.”
    Quote in the paperSubstantial claim
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  • Classified as probably not a substantial claim. 3
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    Premisecitation

    Aspirin and clopidogrel-based dual antiplatelet responsiveness can be reduced in type 2 diabetes, and chronic kidney disease worsens this.

    “responsiveness to aspirin40 and clopidogrel-based dual antiplatelet therapy41 may be impaired in the setting of T2DM,41,42 which is further exacerbated in patients with concomitant chronic kidney disease.43”
    Quote in the paperSubstantial claim0 of 4 sources checked
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    Premisecitation

    Faster platelet clearance shortens platelet lifespan and increases the proportion of large, immature circulating platelets.

    “Increased platelet clearance results in a reduced platelet life span and a relative preponderance of large, immature circulating platelets.34,35”
    Quote in the paperNot a substantial claim0 of 2 sources checked
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    Premisecitation

    Higher glycoprotein IIb/IIIa receptor density and hyperglycemia-driven increases in adhesion molecules intensify thrombotic tendency and raise cardiovascular risk.

    “Increased glycoprotein IIb/IIIa receptor density,36 along with hyperglycemia-mediated increases in adhesion molecules such as von Willebrand factor, vitronectin, and p-selectin,37,38 furthers this thrombotic propensity and elevates cardiovascular risk.26,39”
    Quote in the paperNot a substantial claim0 of 4 sources checked
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    Premisecitation

    In COMPASS, rivaroxaban increased bleeding, though fatal bleeding was not significantly increased.

    “There was an associated increased risk of bleeding with rivaroxaban, although no significant excess in fatal bleeding was noted.”
    Quote in the paperSubstantial claim0 of 4 sources checked
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    Premisecitation

    More frequent or higher-dose antithrombotic regimens may partly overcome reduced responsiveness in type 2 diabetes, but their safety is unproven.

    “Because of the increased platelet turnover in patients with T2DM, the decreased responsiveness to antithrombotic medications be improved somewhat by more frequent and higher dosing regimens,44–46 although the safety of such alternative regimens is not proven.”
    Quote in the paperSubstantial claim0 of 3 sources checked
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    Premisecitation

    In THEMIS, ticagrelor's efficacy and net clinical benefit were better in patients with prior percutaneous coronary intervention.

    “Notably, the efficacy and net clinical benefit of ticagrelor were more favorable among patients from THEMIS who had a history of percutaneous coronary intervention (PCI).55”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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    Premisecitation

    In THEMIS, among 19,271 patients with type 2 diabetes and coronary disease without prior myocardial infarction or stroke, ticagrelor plus aspirin lowered the composite of cardiovascular death, myocardial infarction, or stroke over about 40 months (7.7% vs 8.5%; P=0.04) but raised TIMI major bleeding (2.2% vs 1.0%; P<0.001).

    “Patients randomized to ticagrelor had a lower risk of the composite of cardiovascular death, myocardial infarction, or stroke over an average follow-up of 40 months (ticagrelor versus placebo: 7.7% versus 8.5%; P=0.04), whereas the incidence of TIMI (Thrombolysis in Myocardial Infarction) major bleeding was higher (2.2% versus 1.0%; P<0.001).54”
    Quote in the paperSubstantial claim0 of 1 sources checked
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    Premisecitation

    Abnormal platelet receptor density and signaling affecting adhesion, activation, and aggregation lead to greater platelet activity and weaker antiplatelet treatment effects.

    “dysregulation of platelet receptor density and signaling effects on adhesion, activation, and aggregation30 result in enhanced platelet activity31 and impaired antiplatelet therapeutic effect.32,33”
    Quote in the paperSubstantial claim0 of 4 sources checked
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    Premisecitation

    Hyperglycemia and hyperinsulinemia change the endothelium, disrupting nitric oxide regulation and promoting a proinflammatory, vasoconstrictive state that favors atherothrombosis.

    “Both hyperglycemia and hyperinsulinemia alter the endothelium,27 disrupting the normal atheroprotective nitric oxide regulatory environment and encouraging a generalized proinflammatory, vasoconstrictive state predisposing to atherothrombosis.27–29”
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    Interpretationcitation

    Because rivaroxaban's ischemic benefit was consistent in the diabetes subgroup, low-dose anticoagulation added to antiplatelet therapy may be another secondary prevention option in type 2 diabetes with stable coronary disease.

    “The ischemic benefits of rivaroxaban were consistent in the subgroup with diabetes mellitus, suggesting that low-dose anticoagulation added to antiplatelet therapy may be another option for secondary prevention in patients with T2DM and stable CAD.”
    Quote in the paperSubstantial claim0 of 4 sources checked
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    Premisecitation

    Uptake of newer risk-reduction strategies in practice has been slow, and major care quality gaps persist.

    “their adoption in clinical practice has been slow, and large gaps in the quality of care remain.20”
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    Premisecitation

    ACE inhibitors or ARBs slow kidney disease progression in albuminuria with urine albumin-to-creatinine ratio at least 30 mg/g and reduce incident and recurrent atherosclerotic ischemic events.

    “ACE inhibitors/ARBs reduce the progression of kidney disease in patients with albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g)5 and reduce the risk of both incident and recurrent atherosclerotic ischemic events.79,80”
    Quote in the paperSubstantial claim0 of 3 sources checked
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    Premisecitation

    Cardiovascular risk in type 2 diabetes is considerably elevated, partly because diabetic dyslipidemia creates a proatherogenic environment through an abnormal lipoprotein profile.

    “Cardiovascular risk in T2DM is considerably elevated, at least in part as a result of the proatherogenic milieu of diabetic dyslipidemia that arises primarily from a deranged lipoprotein profile.99”
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    Premisecitation

    Thiazide diuretics worsen glycemic control by reducing insulin sensitivity and secretion, though the clinical importance is debated because blood pressure trials with these drugs showed favorable cardiovascular outcomes.

    “Thiazide diuretics are well known to worsen glycemic control through a reduction in both insulin sensitivity and secretion,85–88 although the clinical implications of this effect are still questioned, given the favorable cardiovascular outcomes in blood pressure trials with these agents.86”
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    Premisecitation

    Mineralocorticoid receptor antagonists can lower blood pressure, especially with borderline or low potassium, and reduce morbidity and mortality in left ventricular dysfunction.

    “Mineralocorticoid receptor antagonists (spironolactone, eplerenone) can also be effective antihypertensive agents (particularly for those with borderline or low potassium levels)89 and are important for morbidity and mortality reduction in patients with left ventricular dysfunction.90,91”
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    Premisecitation

    Type 2 diabetes patients were explicitly excluded from SPRINT, making it hard to know whether SPRINT findings apply to type 2 diabetes with coronary disease.

    “Importantly, at least in part due to the ACCORD trial (Action to Control Cardiovascular Risk in Diabetes),72 patients with T2DM were explicitly excluded from SPRINT, so it is difficult to determine whether the results of SPRINT can extend to patients with T2DM and CAD.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [72] ACCORD Study Group, Cushman WC, Evans GW, Byington RP, Goff DC Jr, Grimm RH Jr, Cutler JA, Simons-Morton DG, Basile JN, Corson MA, Probstfield JL, Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010; 362: 1575– 1585. doi: 10.1056/NEJMoa1001286 20228401 PMC4123215 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Hypertension is about twice as common in type 2 diabetes as in the general population, and 70%-80% of type 2 diabetes patients have it.

    “The prevalence of hypertension in patients with T2DM is ≈2-fold greater than in the general population, with the vast majority of patients with T2DM (70%–80%) having concomitant hypertension.63”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [63] Fox CS, Golden SH, Anderson C, Bray GA, Burke LE, de Boer IH, Deedwania P, Eckel RH, Ershow AG, Fradkin J,; on behalf of the American Heart Association Diabetes Committee of the Council on Lifestyle and Cardiometabolic Health, Council on Clinical Cardiology, Council on Cardiovascular and Stroke Nursing, Council on Cardiovascular Surgery and Anesthesia, Council on Quality of Care and Outcomes Research, and the American Diabetes Association. Update on prevention of cardiovascular disease in adults with type 2 diabetes mellitus in light of recent evidence: a scientific statement from the American source

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  • May combine two claims.

    Premisecitation

    Intensive blood pressure lowering appears to affect coronary and cerebral events differently, and effects vary with comorbidities such as recent acute coronary syndrome.

    “There appears to be heterogeneity in the impact of intensive blood pressure lowering on coronary versus cerebral events, and the effects can also vary based on comorbid conditions (eg, recent acute coronary syndrome).64,65,76”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [64] Deedwania PC. Blood pressure control in diabetes mellitus: is lower always better, and how low should it go? Circulation. 2011; 123: 2776– 2778. doi: 10.1161/CIRCULATIONAHA.111.033704 21690500 source

      Not checked in the free run.

    • cites [65] Deedwania P. The ongoing saga of optimal blood pressure level in patients with diabetes mellitus and coronary artery disease. J Am Heart Assoc. 2018; 7: e010752. doi: 10.1161/JAHA.118.010752 30371267 PMC6474965 source

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    • cites [76] Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW, 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018; 138: e484– e594. doi: 10.1161/CIR.0000000000000596 30354654 source

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  • May combine two claims.

    Premisecitation

    In HOPE, ramipril lowered myocardial infarction by 22% (95% CI 6-36), stroke by 33% (95% CI 10-50), and cardiovascular death by 37% (95% CI 21-51) in diabetes patients with cardiovascular disease or another risk factor but no proteinuria or heart failure, independently of blood pressure changes.

    “The trial was stopped early (after 4.5 years) because of consistent benefit of ramipril, which was shown to reduce the risk of myocardial infarction by 22% (95% CI, 6–36), stroke by 33% (95% CI, 10–50), and cardiovascular death by 37% (95% CI, 21–51), findings that were independent of changes in blood pressure.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [81] Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy: Heart Outcomes Prevention Evaluation Study Investigators. Lancet. 2000; 355: 253– 259. 10675071

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  • May combine two claims.

    Premisecitation

    Intensive blood pressure lowering showed benefit in SPRINT's prediabetes subgroup, in a later meta-analysis, and in a large observational study in which 13% had diabetes.

    “There was evidence of benefit of intensive blood pressure lowering in the prediabetes cohort of SPRINT,71 a subsequent meta-analysis,73 and a recent large observational study (13% with diabetes mellitus).73a,74”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites 71,73,73a,74

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    Premisecitation

    Later trials of lowering blood pressure below 130 mm Hg in type 2 diabetes and hypertension found no meaningful reduction in coronary events, though stroke risk fell.

    “However, subsequent trials that specifically examined the role of a blood pressure lowering strategy to <130 mm Hg in patients with T2DM and hypertension found no substantive benefit of intensive blood pressure control in reducing the risk of coronary events, although there was evidence for decreased risk of stroke.5,66–69”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [5] American Diabetes Association. 10: Cardiovascular disease and risk management: Standards of Medical Care in Diabetes–2019. Diabetes Care. 2019; 42: S103– S123. doi: 10.2337/dc19-S010 30559236 source

      Not checked in the free run.

    • cites [66] Cooper-DeHoff RM, Gong Y, Handberg EM, Bavry AA, Denardo SJ, Bakris GL, Pepine CJ. Tight blood pressure control and cardiovascular outcomes among hypertensive patients with diabetes and coronary artery disease. JAMA. 2010; 304: 61– 68. doi: 10.1001/jama.2010.884 20606150 PMC3008411 source

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    • cites [67] Vidal-Petiot E, Ford I, Greenlaw N, Ferrari R, Fox KM, Tardif JC, Tendera M, Tavazzi L, Bhatt DL, Steg PG; CLARIFY Investigators. Cardiovascular event rates and mortality according to achieved systolic and diastolic blood pressure in patients with stable coronary artery disease: an international cohort study. Lancet. 2016; 388: 2142– 2152. doi: 10.1016/S0140-6736(16)31326-5 27590221 source

      Not checked in the free run.

    • cites [68] Böhm M, Schumacher H, Teo KK, Lonn EM, Mahfoud F, Mann JFE, Mancia G, Redon J, Schmieder RE, Sliwa K, Achieved blood pressure and cardiovascular outcomes in high-risk patients: results from ONTARGET and TRANSCEND trials. Lancet. 2017; 389: 2226– 2237. doi: 10.1016/S0140-6736(17)30754-7 28390695 source

      Not checked in the free run.

    • cites [69] Bangalore S, Kumar S, Lobach I, Messerli FH. Blood pressure targets in subjects with type 2 diabetes mellitus/impaired fasting glucose: observations from traditional and bayesian random-effects meta-analyses of randomized trials. Circulation. 2011; 123: 2799– 2810, 9 p following 810. doi: 10.1161/CIRCULATIONAHA.110.016337 21632497 source

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  • May combine two claims.

    Premisecitation

    The observed stroke reduction agrees with observational evidence of a linear systolic blood pressure-stroke relationship, with lower stroke risk when systolic pressure falls below 120 mm Hg.

    “The observed stroke reduction is consistent with observational data that have shown a linear relationship between systolic blood pressure and risk of stroke, with a decrease in stroke risk with lowering of systolic blood pressure to levels <120 mm Hg.64,65”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [64] Deedwania PC. Blood pressure control in diabetes mellitus: is lower always better, and how low should it go? Circulation. 2011; 123: 2776– 2778. doi: 10.1161/CIRCULATIONAHA.111.033704 21690500 source

      Not checked in the free run.

    • cites [65] Deedwania P. The ongoing saga of optimal blood pressure level in patients with diabetes mellitus and coronary artery disease. J Am Heart Assoc. 2018; 7: e010752. doi: 10.1161/JAHA.118.010752 30371267 PMC6474965 source

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  • May combine two claims.

    Interpretationcitation

    Cumulative FOURIER and ODYSSEY OUTCOMES data suggest PCSK9 inhibitors lower LDL cholesterol and cardiovascular risk effectively in coronary disease regardless of diabetes status.

    “the cumulative data from the FOURIER and ODYSSEY OUTCOMES trials suggest that PCSK9 inhibitors effectively lower LDL-C and cardiovascular risk in individuals with CAD regardless of diabetes mellitus status.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [9] Sabatine MS, Leiter LA, Wiviott SD, Giugliano RP, Deedwania P, De Ferrari GM, Murphy SA, Kuder JF, Gouni-Berthold I, Lewis BS, Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: a prespecified analysis of the FOURIER randomised controlled trial. Lancet Diabetes Endocrinol. 2017; 5: 941– 950. doi: 10.1016/S2213-8587(17)30313-3 28927706 source

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    • cites [14] Ray KK, Colhoun HM, Szarek M, Baccara-Dinet M, Bhatt DL, Bittner VA, Budaj AJ, Diaz R, Goodman SG, Hanotin C,; ODYSSEY OUTCOMES Committees and Investigators. Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial. Lancet Diabetes Endocrinol. 2019; 7: 618– 628. 31272931 source

      Not checked in the free run.

    • cites [125] Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, Kuder JF, Wang H, Liu T, Wasserman SM,; FOURIER Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017; 376: 1713– 1722. doi: 10.1056/NEJMoa1615664 28304224 source

      Not checked in the free run.

    • cites [126] Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, Edelberg JM, Goodman SG, Hanotin C, Harrington RA,; ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018; 379: 2097– 2107. doi: 10.1056/NEJMoa1801174 30403574 source

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  • May combine two claims.

    Premisecitation

    In the CTT collaboration, diabetes patients had a 22% relative reduction in major coronary events (RR 0.78 [95% CI 0.69-0.87]; P<0.0001) per 39-mg/dL LDL cholesterol decrease, indistinguishable from those without diabetes.

    “there was a 22% RR reduction (RRR) in major coronary events (RR, 0.78 [95% CI, 0.69–0.87]; P<0.0001) per 39-mg/dL (1-mmol/L) LDL-C decrease among those with diabetes mellitus,113 an effect that was indistinguishable for the groups with and without diabetes mellitus.114”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [113] Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, Kirby A, Sourjina T, Peto R, Collins R,; Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005; 366: 1267– 1278. doi: 10.1016/S0140-6736(05)67394-1 16214597 source

      Not checked in the free run.

    • cites [114] Cholesterol Treatment Trialists Collaborators, Kearney PM, Blackwell L, Collins R, Keech A, Simes J, Peto R, Armitage J, Baigent C. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet. 2008; 371: 117– 125. doi: 10.1016/S0140-6736(08)60104-X 18191683 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In FOURIER, evolocumab produced comparable LDL cholesterol reductions (57% vs 60%) and relative risk reductions (27% vs 23%) for the primary composite end point in patients with versus without diabetes.

    “In patients with versus without diabetes mellitus, with evolocumab, there were comparable LDL-C reductions (57% versus 60% mean reductions) and RRRs (27% versus 23% RRR) in the primary composite end point of cardiovascular death, myocardial infarction, stroke, and hospitalization for unstable angina or revascularization.9”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [9] Sabatine MS, Leiter LA, Wiviott SD, Giugliano RP, Deedwania P, De Ferrari GM, Murphy SA, Kuder JF, Gouni-Berthold I, Lewis BS, Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: a prespecified analysis of the FOURIER randomised controlled trial. Lancet Diabetes Endocrinol. 2017; 5: 941– 950. doi: 10.1016/S2213-8587(17)30313-3 28927706 source

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  • May combine two claims.

    Premisecitation

    The modest statin-associated risk of incident type 2 diabetes is lower than that with thiazide diuretics or nonvasodilating beta-blockers and is far outweighed by statins' cardiovascular protection.

    “This modest risk has been shown to be lower than the risk of incident T2DM associated with thiazide diuretics or nonvasodilating β-blockers116 and, most important, is far overshadowed by the cardiovascular protective effect of statin therapy.117,118”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [116] Elliott WJ, Meyer PM. Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet. 2007; 369: 201– 207. doi: 10.1016/S0140-6736(07)60108-1 17240286 source

      Not checked in the free run.

    • cites [117] Waters DD, Ho JE, Boekholdt SM, DeMicco DA, Kastelein JJ, Messig M, Breazna A, Pedersen TR. Cardiovascular event reduction versus new-onset diabetes during atorvastatin therapy: effect of baseline risk factors for diabetes. J Am Coll Cardiol. 2013; 61: 148– 152. doi: 10.1016/j.jacc.2012.09.042 23219296 source

      Not checked in the free run.

    • cites [118] Kearney PM, Blackwell L, Collins R, Keech A, Simes J, Peto R, Armitage J, Baigent C; Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet. 2008; 371: 117– 125. doi: 10.1016/S0140-6736(08)60104-X 18191683 source

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  • May combine two claims.

    Premisecitation

    Neither PCSK9 inhibitor reduced cardiovascular mortality in FOURIER or ODYSSEY OUTCOMES.

    “Although neither PCSK9 inhibitor reduced cardiovascular mortality in these trials,125,126”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [125] Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, Kuder JF, Wang H, Liu T, Wasserman SM,; FOURIER Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017; 376: 1713– 1722. doi: 10.1056/NEJMoa1615664 28304224 source

      Not checked in the free run.

    • cites [126] Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, Edelberg JM, Goodman SG, Hanotin C, Harrington RA,; ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018; 379: 2097– 2107. doi: 10.1056/NEJMoa1801174 30403574 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    LDL cholesterol levels in type 2 diabetes are often similar to those without diabetes, but hypertriglyceridemia promotes LDL oxidation and hyperglycemia drives LDL glycation, making LDL more atherogenic.

    “LDL cholesterol (LDL-C) levels in individuals with T2DM are often similar to those in individuals without T2DM, but the persistent hypertriglyceridemic state promotes LDL oxidation, and the concurrent hyperglycemia drives LDL glycation, all of which increase the atherogenicity of the LDL particles in T2DM.100”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [100] Vergès B. Pathophysiology of diabetic dyslipidaemia: where are we? Diabetologia. 2015; 58: 886– 899. doi: 10.1007/s00125-015-3525-8 25725623 PMC4392164 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A large body of evidence shows that statin strategies produce similar LDL cholesterol lowering and relative cardiovascular risk reduction in people with and without type 2 diabetes.

    “A large body of evidence indicates that statin-based strategies convey similar LDL-C lowering and relative cardiovascular risk reduction in patients with and those without T2DM.102–112”
    Quote in the paperSubstantial claim0 of 10 sources checked
    • cites [102] Collins R, Armitage J, Parish S, Sleigh P, Peto R; Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet. 2003; 361: 2005– 2016. doi: 10.1016/s0140-6736(03)13636-7 12814710 source

      Not checked in the free run.

    • cites [103] Long-Term Intervention with Pravastatin in Ischaemic Disease Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998; 339: 1349– 1357. 9841303 source

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    • cites [104] Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, Brown L, Warnica JW, Arnold JM, Wun CC, The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels: Cholesterol and Recurrent Events Trial investigators. N Engl J Med. 1996; 335: 1001– 1009. doi: 10.1056/NEJM199610033351401 8801446 source

      Not checked in the free run.

    • cites [105] Brugts JJ, Yetgin T, Hoeks SE, Gotto AM, Shepherd J, Westendorp RG, de Craen AJ, Knopp RH, Nakamura H, Ridker P, The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials. BMJ. 2009; 338: b2376. doi: 10.1136/bmj.b2376 19567909 PMC2714690 source

      Not checked in the free run.

    • cites [106] Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, Thomason MJ, Mackness MI, Charlton-Menys V, Fuller JH; CARDS Investigators. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004; 364: 685– 696. doi: 10.1016/S0140-6736(04)16895-5 15325833 source

      Not checked in the free run.

    • cites [107] Costa J, Borges M, David C, Vaz Carneiro A. Efficacy of lipid lowering drug treatment for diabetic and non-diabetic patients: meta-analysis of randomised controlled trials. BMJ. 2006; 332: 1115– 1124. doi: 10.1136/bmj.38793.468449.AE 16585050 PMC1459619 source

      Not checked in the free run.

    • cites [108] Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002; 360: 7– 22. doi: 10.1016/S0140-6736(02)09327-3 12114036 source

      Not checked in the free run.

    • cites [109] LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC, Gotto AM, Greten H, Kastelein JJ, Shepherd J,; Treating to New Targets (TNT) Investigators. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005; 352: 1425– 1435. doi: 10.1056/NEJMoa050461 15755765 source

      Not checked in the free run.

    • cites [110] Leiter LA, Betteridge DJ, Farnier M, Guyton JR, Lin J, Shah A, Johnson-Levonas AO, Brudi P. Lipid-altering efficacy and safety profile of combination therapy with ezetimibe/statin vs. statin monotherapy in patients with and without diabetes: an analysis of pooled data from 27 clinical trials. Diabetes Obes Metab. 2011; 13: 615– 628. doi: 10.1111/j.1463-1326.2011.01383.x 21332628 source

      Not checked in the free run.

    • cites [111] Pyŏrälä K, Pedersen TR, Kjekshus J, Faergeman O, Olsson AG, Thorgeirsson G. Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease: a subgroup analysis of the Scandinavian Simvastatin Survival Study (4S). Diabetes Care. 1997; 20: 614– 620. doi: 10.2337/diacare.20.4.614 9096989 source

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  • May combine two claims.

    Premisecitation

    In IMPROVE-IT, adding ezetimibe to simvastatin after acute coronary syndrome lowered LDL cholesterol by an additional 17 mg/dL and was linked to a 2.0% absolute and 6.4% relative reduction in the primary composite of cardiovascular death, major coronary event, or stroke after median 6 years.

    “Specifically, the addition of 10 mg ezetimibe to 40 mg simvastatin within 10 days of hospitalization for an acute coronary syndrome lowered LDL-C levels by an additional 17 mg/dL (0.4 mmol/L), which was associated with an overall modest, but significant, 2.0% absolute/6.4% relative reduction in the primary composite end point of cardiovascular death, major coronary event, or stroke after a median”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [13] Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, Darius H, Lewis BS, Ophuis TO, Jukema JW,; IMPROVE-IT Investigators. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015; 372: 2387– 2397. doi: 10.1056/NEJMoa1410489 26039521 source

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    Premisecitation

    Typical type 2 diabetes lipid abnormalities include hypertriglyceridemia that promotes small dense LDL particles, reduced HDL cholesterol from enhanced catabolism, and a predominance of large VLDL particles from a synthesis-catabolism imbalance.

    “Typical lipid anomalies in T2DM include hypertriglyceridemia, which promotes the presence of small, dense low-density lipoprotein (LDL) particles; reduced levels of high-density lipoprotein cholesterol caused by enhanced high-density lipoprotein cholesterol catabolism; and a predominance of large very LDL particles resulting from a synthesis-catabolism imbalance.100”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [100] Vergès B. Pathophysiology of diabetic dyslipidaemia: where are we? Diabetologia. 2015; 58: 886– 899. doi: 10.1007/s00125-015-3525-8 25725623 PMC4392164 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The proposed linear link between LDL cholesterol lowering and cardiovascular risk reduction, plus limited long-term safety data at very low LDL cholesterol, supports aiming for low LDL cholesterol in highest-risk patients without raising adverse event risk.

    “supports the notion of aiming for low LDL-C levels, especially in those patients with the highest absolute risk of a recurrent event (eg, T2DM, peripheral artery disease, recent incident of acute coronary syndrome, and multiple prior cardiovascular events), but not at the expense of elevating the risk of adverse events.127”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [127] Cholesterol Treatment Trialists Collaboration, Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010; 376: 1670– 1681. doi: 10.1016/S0140-6736(10)61350-5 21067804 PMC2988224 source

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    Premisecitation

    Sattar and colleagues reported that four years of statin treatment produced one extra type 2 diabetes case per 255 people while preventing 5.4 vascular events.

    “Sattar and colleagues115 reported that although statin treatment for 4 years yielded 1 extra case of T2DM in a group of 255 individuals, 5.4 vascular events were concomitantly prevented.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [115] Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, Seshasai SR, McMurray JJ, Freeman DJ, Jukema JW, Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010; 375: 735– 742. doi: 10.1016/S0140-6736(09)61965-6 20167359 source

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  • May combine two claims.

    Premisecitation

    In FOURIER, evolocumab did not increase incident type 2 diabetes and did not change fasting plasma glucose or HbA1c over median 2.2 years.

    “There were also no increase in incident T2DM and no changes in fasting plasma glucose or HbA1c over the median 2.2 years of follow-up.9”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [9] Sabatine MS, Leiter LA, Wiviott SD, Giugliano RP, Deedwania P, De Ferrari GM, Murphy SA, Kuder JF, Gouni-Berthold I, Lewis BS, Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: a prespecified analysis of the FOURIER randomised controlled trial. Lancet Diabetes Endocrinol. 2017; 5: 941– 950. doi: 10.1016/S2213-8587(17)30313-3 28927706 source

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  • May combine two claims.

    Premisecitation

    Other studies of exercise-based interventions in patients with type 2 diabetes and coronary artery disease have shown no significant improvements in HbA1c or exercise capacity and poor adherence.

    “others have shown no significant improvements in HbA1c or exercise capacity and poor adherence to the intervention”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [156] Karjalainen JJ, Kiviniemi AM, Hautala AJ, Piira OP, Lepojärvi ES, Perkiömäki JS, Junttila MJ, Huikuri HV, Tulppo MP. Effects of physical activity and exercise training on cardiovascular risk in coronary artery disease patients with and without type 2 diabetes. Diabetes Care. 2015; 38: 706– 715. doi: 10.2337/dc14-2216 25592198 source

      Not checked in the free run.

    • cites [166] Byrkjeland R, Njerve IU, Anderssen S, Arnesen H, Seljeflot I, Solheim S. Effects of exercise training on HbA1c and VO2peak in patients with type 2 diabetes and coronary artery disease: a randomised clinical trial. Diab Vasc Dis Res. 2015; 12: 325– 333. doi: 10.1177/1479164115590552 26092822 source

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  • May combine two claims.

    Premisecitation

    Lower physical activity and lower exercise capacity are associated with a higher risk of cardiovascular events.

    “factors associated with a higher risk of cardiovascular events”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [156] Karjalainen JJ, Kiviniemi AM, Hautala AJ, Piira OP, Lepojärvi ES, Perkiömäki JS, Junttila MJ, Huikuri HV, Tulppo MP. Effects of physical activity and exercise training on cardiovascular risk in coronary artery disease patients with and without type 2 diabetes. Diabetes Care. 2015; 38: 706– 715. doi: 10.2337/dc14-2216 25592198 source

      Not checked in the free run.

    • cites [157] Beatty AL, Schiller NB, Whooley MA. Six-minute walk test as a prognostic tool in stable coronary heart disease: data from the Heart and Soul Study. Arch Intern Med. 2012; 172: 1096– 1102. doi: 10.1001/archinternmed.2012.2198 22710902 PMC3420342 source

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  • May combine two claims.

    Premisecitation

    Compared with patients without type 2 diabetes, patients with type 2 diabetes who enroll in cardiac rehabilitation have a greater risk factor burden and lower exercise capacity at baseline.

    “patients with T2DM who enroll in cardiac rehabilitation have a greater risk factor burden and lower exercise capacity at baseline”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [161] Suresh V, Harrison RA, Houghton P, Naqvi N. Standard cardiac rehabilitation is less effective for diabetics. Int J Clin Pract. 2001; 55: 445– 448. 11594253 source

      Not checked in the free run.

    • cites [162] Banzer JA, Maguire TE, Kennedy CM, O’Malley CJ, Balady GJ. Results of cardiac rehabilitation in patients with diabetes mellitus. Am J Cardiol. 2004; 93: 81– 84. doi: 10.1016/j.amjcard.2003.09.017 14697472 source

      Not checked in the free run.

    • cites [163] Mourot L, Boussuges A, Maunier S, Chopra S, Rivière F, Debussche X, Blanc P. Cardiovascular rehabilitation in patients with diabetes. J Cardiopulm Rehabil Prev. 2010; 30: 157– 164. doi: 10.1097/HCR.0b013e3181c565fe 20040882 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In REDUCE-IT, icosapent ethyl significantly reduced the composite of cardiovascular death, nonfatal myocardial infarction, stroke, coronary revascularization, or unstable angina, with similar effects in patients with diabetes (HR 0.77 [95% CI 0.68-0.87]) and without diabetes (HR 0.73 [95% CI 0.62-0.85]).

    “Overall, there was a significant reduction in the risk of the composite of cardiovascular death, nonfatal myocardial infarction, stroke, coronary revascularization, or unstable angina with icosapent ethyl, an effect that was similar in those with diabetes mellitus (HR, 0.77 [95% CI, 0.68–0.87]) and those without diabetes mellitus (HR, 0.73 [95% CI, 0.62–0.85]).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT Jr, Juliano RA, Jiao L, Granowitz C,; REDUCE-IT Investigators. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019; 380: 11– 22. doi: 10.1056/NEJMoa1812792 30415628 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Treatment of obstructive sleep apnea may reduce blood pressure and have other beneficial cardiometabolic effects.

    “Treatment of obstructive sleep apnea may reduce blood pressure and have other beneficial cardiometabolic effects”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [152] Gottlieb DJ, Punjabi NM, Mehra R, Patel SR, Quan SF, Babineau DC, Tracy RP, Rueschman M, Blumenthal RS, Lewis EF, CPAP versus oxygen in obstructive sleep apnea. N Engl J Med. 2014; 370: 2276– 2285. doi: 10.1056/NEJMoa1306766 24918372 PMC4172401 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Diets rich in low-carbohydrate and low-glycemic-index foods may improve both glycemic control and cardiovascular risk factors.

    “There is also evidence that diets rich in low-carbohydrate and low-glycemic-index foods may improve both glycemic control and cardiovascular risk factors.146,147”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [146] Esposito K, Maiorino MI, Bellastella G, Chiodini P, Panagiotakos D, Giugliano D. A journey into a Mediterranean diet and type 2 diabetes: a systematic review with meta-analyses. BMJ Open. 2015; 5: e008222. doi: 10.1136/bmjopen-2015-008222 PMC4538272 26260349 source

      Not checked in the free run.

    • cites [147] Sacks FM, Carey VJ, Anderson CA, Miller ER 3rd, Copeland T, Charleston J, Harshfield BJ, Laranjo N, McCarron P, Swain J, Effects of high vs low glycemic index of dietary carbohydrate on cardiovascular disease risk factors and insulin sensitivity: the OmniCarb randomized clinical trial. JAMA. 2014; 312: 2531– 2541. doi: 10.1001/jama.2014.16658 25514303 PMC4370345 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Smoking cessation can substantially lower recurrent coronary artery disease event risk, reaching the risk level of nonsmokers by about three years after quitting.

    “However, smoking cessation can substantially reduce the risk of recurrent CAD events, declining to the level of risk of nonsmokers by ≈3 years after cessation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [141] Al-Delaimy WK, Manson JE, Solomon CG, Kawachi I, Stampfer MJ, Willett WC, Hu FB. Smoking and risk of coronary heart disease among women with type 2 diabetes mellitus. Arch Intern Med. 2002; 162: 273– 279. doi: 10.1001/archinte.162.3.273 11822919 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In PREDIMED, a Mediterranean diet supplemented with extravirgin olive oil or mixed nuts reduced the primary composite of cardiovascular death, myocardial infarction, or stroke by 30%, with similar results in type 2 diabetes patients.

    “The trial was stopped early because of a 30% reduction in the primary composite outcome of cardiovascular death, myocardial infarction, or stroke observed with the Mediterranean diet, results that were similar in patients with T2DM.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [145] Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, Gómez-Gracia E, Ruiz-Gutiérrez V, Fiol M, Lapetra J,; PREDIMED Study Investigators. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013; 368: 1279– 1290. doi: 10.1056/NEJMoa1200303 29897867 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Bariatric surgery has risks, which are likely higher in patients with existing coronary artery disease.

    “Although bariatric surgery has risks,178 which are likely higher in patients with existing CAD”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [178] Sjöström L, Peltonen M, Jacobson P, Ahlin S, Andersson-Assarsson J, Anveden Å, Bouchard C, Carlsson B, Karason K, Lönroth H, Association of bariatric surgery with long-term remission of type 2 diabetes and with microvascular and macrovascular complications. JAMA. 2014; 311: 2297– 2304. doi: 10.1001/jama.2014.5988 24915261 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Intense efforts to achieve HbA1c <7% among patients with long-standing type 2 diabetes increase risks associated with polypharmacy, contribute to treatment burden, and may increase the risk of hypoglycemia.

    “The relatively intense efforts to achieve an HbA1c <7% among patients with long-standing T2DM increase the risks associated with polypharmacy, contribute to treatment burden (including financial burden), and may increase the risk of hypoglycemia.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [192] Lipska KJ, Krumholz H, Soones T, Lee SJ. Polypharmacy in the aging patient: a review of glycemic control in older adults with type 2 diabetes. JAMA. 2016; 315: 1034– 1045. doi: 10.1001/jama.2016.0299 26954412 PMC4823136 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Although sulfonylureas have been associated with increased cardiovascular mortality in retrospective observational studies, most large controlled clinical trials have generally proved sulfonylureas, particularly second-generation agents, to be safe and cardiovascular neutral.

    “although sulfonylureas have been associated with increased cardiovascular mortality in retrospective observational studies, most large controlled clinical trials have generally proved sulfonylureas (particularly second-generation agents) to be safe and cardiovascular neutral”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [183] Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, Marre M, Cooper M, Glasziou P, Grobbee D, Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008; 358: 2560– 2572. 18539916 source

      Not checked in the free run.

    • cites [187] Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33): UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998; 352: 837– 853. 9742976

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [203] Vaccaro O, Masulli M, Nicolucci A, Bonora E, Del Prato S, Maggioni AP, Rivellese AA, Squatrito S, Giorda CB, Sesti G,; Thiazolidinediones Or Sulfonylureas Cardiovascular Accidents Intervention Trial (TOSCA.IT) Study Group; Italian Diabetes Society. Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately controlled with metformin (TOSCA.IT): a randomised, multicentre trial. Lancet Diabetes Endocrinol. 2017; 5: 887– 897. doi: 10.1016/S2213-8587(17)30317-0 28917544 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Glycemic control, if instituted early in the course of type 2 diabetes, may lower the risk of cardiovascular events, but the effect is modest.

    “the findings suggest that glycemic control, if instituted early in the course of T2DM, may lower the risk of cardiovascular events, but the effect is modest”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The strategy used to achieve glycemic control matters because the total effect of a specific glucose-lowering agent is not conveyed by the degree to which it lowers glucose.

    “The results of these studies suggest that the strategy used to achieve glycemic control matters because the total effect of a specific glucose-lowering agent is not conveyed by the degree to which it lowers glucose.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Intensive glycemic control generally reduces the risk of microvascular end points, even if it does not reduce major cardiovascular events.

    “intensive glycemic control generally reduces the risk of microvascular end points, even if it does not reduce major cardiovascular events”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [187] Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33): UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998; 352: 837– 853. 9742976

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [182] Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, Zieve FJ, Marks J, Davis SN, Hayward R,; VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009; 360: 129– 139. doi: 10.1056/NEJMoa0808431 19092145 source

      Not checked in the free run.

    • cites [183] Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, Marre M, Cooper M, Glasziou P, Grobbee D, Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008; 358: 2560– 2572. 18539916 source

      Not checked in the free run.

    • cites [184] Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH Jr, Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008; 358: 2545– 2559. 18539917 PMC4551392 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    These trials included substantial proportions of patients with established macrovascular disease (ACCORD, 35.2%; ADVANCE, 32.3%; VADT, 40.3%) and generally targeted HbA1c levels <6.5%.

    “These trials included a substantial proportion of patients with established macrovascular disease (ACCORD, 35.2%; ADVANCE [Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation], 32.3%; and VADT [Veterans Affairs Diabetes Trial], 40.3%) and generally targeted HbA1c levels <6.5%.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [182] Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, Zieve FJ, Marks J, Davis SN, Hayward R,; VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009; 360: 129– 139. doi: 10.1056/NEJMoa0808431 19092145 source

      Not checked in the free run.

    • cites [183] Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, Marre M, Cooper M, Glasziou P, Grobbee D, Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008; 358: 2560– 2572. 18539916 source

      Not checked in the free run.

    • cites [184] Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH Jr, Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008; 358: 2545– 2559. 18539917 PMC4551392 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The other two trials demonstrated no benefit for major cardiovascular events, with no heterogeneity of effect based on the presence or absence of established macrovascular disease.

    “The other 2 trials demonstrated no benefit with respect to the primary outcome, major cardiovascular events, with no heterogeneity of effect based on the presence or absence of established macrovascular disease.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [182] Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, Zieve FJ, Marks J, Davis SN, Hayward R,; VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009; 360: 129– 139. doi: 10.1056/NEJMoa0808431 19092145 source

      Not checked in the free run.

    • cites [183] Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, Marre M, Cooper M, Glasziou P, Grobbee D, Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008; 358: 2560– 2572. 18539916 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In UKPDS, more intensive glycemic control (median achieved HbA1c 7.0%) compared with standard treatment (HbA1c 7.9%) was associated with a reduction in myocardial infarction risk (RR, 0.84 [95% CI, 0.71-1.00]) among newly diagnosed patients with type 2 diabetes, but this did not reach statistical significance (P=0.052).

    “more intensive glycemic control (achieved median HbA1c, 7.0%) compared with standard treatment (HbA1c, 7.9%) was associated with a reduction in the risk for myocardial infarction (RR, 0.84 [95% CI, 0.71–1.00]) among newly diagnosed patients with T2DM, but this did not reach statistical significance (P=0.052)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [187] Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33): UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998; 352: 837– 853. 9742976

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    In IRIS, there was no increased risk of heart failure hospitalizations with pioglitazone, but patients with known heart failure were excluded, and protocols were in place for dose reduction with any signs of fluid overload.

    “in IRIS, there was no increased risk of heart failure hospitalizations with pioglitazone, but patients with known heart failure were excluded, and there were protocols in place for study drug dose reduction with any signs of fluid overload”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [212] Kernan WN, Viscoli CM, Furie KL, Young LH, Inzucchi SE, Gorman M, Guarino PD, Lovejoy AM, Peduzzi PN, Conwit R,; IRIS Trial Investigators. Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. N Engl J Med. 2016; 374: 1321– 1331. doi: 10.1056/NEJMoa1506930 26886418 PMC4887756 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Randomized trials have shown insulin to be associated with a reduced risk of microvascular complications in the context of intensive glycemic control; insulin appears safe from a cardiovascular standpoint but does not reduce adverse cardiovascular events.

    “randomized trials have shown insulin to be associated with a reduced risk of microvascular complications in the context of intensive glycemic control; insulin appears safe from a cardiovascular standpoint, but it does not reduce adverse cardiovascular events”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [184] Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH Jr, Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008; 358: 2545– 2559. 18539917 PMC4551392 source

      Not checked in the free run.

    • cites [187] Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33): UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998; 352: 837– 853. 9742976

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Metformin may improve cardiovascular outcomes and is not associated with either hypoglycemia or weight gain.

    “metformin may actually improve cardiovascular outcomes and is not associated with either hypoglycemia or weight gain”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [188] Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34): UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998; 352: 854– 865. 9742977 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Thiazolidinediones can be used in patients with coronary artery disease but without known heart failure and may have important atherosclerotic benefits; the clinician must be vigilant for signs of fluid overload.

    “Thiazolidinediones can be used in patients with CAD but without known heart failure and may have important atherosclerotic benefits; however, the clinician must be vigilant for any signs of fluid overload”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Thiazolidinediones increase the risk of heart failure because of sodium retention at the distal nephron, and this risk is greater at higher doses and when used with insulin.

  • May combine two claims.

    Premisecitation

    The amputation and bone fracture adverse effects have not been reported with other SGLT2 inhibitors and were not observed in a subsequent trial of canagliflozin.

    “adverse effects that have not been reported to date with other SGLT2 inhibitors and were not observed in a subsequent trial of canagliflozin”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [222] Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, Edwards R, Agarwal R, Bakris G, Bull S,; CREDENCE Trial Investigators. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019; 380: 2295– 2306. doi: 10.1056/NEJMoa1811744 30990260 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Saxagliptin led to a 26% increase in heart failure hospitalization in the SAVOR-TIMI 53 trial, with no clear explanation of the mechanism.

    “saxagliptin, led to a 26% increase in heart failure hospitalization in the SAVOR-TIMI 53 trial (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients With Diabetes Mellitus), with no clear explanation of the mechanism”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [186] Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Frederich R, Wiviott SD, Hoffman EB,; SAVOR-TIMI 53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013; 369: 1317– 1326. doi: 10.1056/NEJMoa1307684 23992601 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In CAROLINA, there was no difference in the risk of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke in patients treated with glimepiride versus linagliptin, albeit with a marked increased risk of hypoglycemia with the sulfonylurea.

    “there was no difference in the risk of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke in patients treated with glimepiride versus linagliptin, albeit with a marked increased risk of hypoglycemia with the sulfonylurea”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [204] Rosenstock J, Kahn SE, Johansen OE, Zinman B, Espeland MA, Woerle HJ, Pfarr E, Keller A, Mattheus M, Baanstra D,; CAROLINA Investigators. Effect of linagliptin vs glimepiride on major adverse cardiovascular outcomes in patients with type 2 diabetes: the CAROLINA randomized clinical trial [published online September 19, 2019]. JAMA. doi: 10.1001/jama.2019.13772. https://jamanetwork.com/journals/jama/article-abstract/2751398. PMC6763993 31536101 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Follow-up studies involving metformin appeared to support a potential cardiovascular benefit, but these studies were small and the findings were not robust.

    “Follow-up studies involving metformin appeared to support a potential cardiovascular benefit, but these studies were small and the findings were not robust.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [207] Hong J, Zhang Y, Lai S, Lv A, Su Q, Dong Y, Zhou Z, Tang W, Zhao J, Cui L,; SPREAD-DIMCAD Investigators. Effects of metformin versus glipizide on cardiovascular outcomes in patients with type 2 diabetes and coronary artery disease. Diabetes Care. 2013; 36: 1304– 1311. doi: 10.2337/dc12-0719 23230096 PMC3631843 source

      Not checked in the free run.

    • cites [208] Kooy A, de Jager J, Lehert P, Bets D, Wulffelé MG, Donker AJ, Stehouwer CD. Long-term effects of metformin on metabolism and microvascular and macrovascular disease in patients with type 2 diabetes mellitus. Arch Intern Med. 2009; 169: 616– 625. doi: 10.1001/archinternmed.2009.20 19307526 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In CANVAS, canagliflozin doubled amputation rates (6.3 versus 3.4 per 1000 person-years) and increased bone fractures.

    “These benefits were somewhat counterbalanced by a doubling of amputation rates (6.3 per 1000 person-years versus 3.4 per 1000 person-years) and more bone fractures in the canagliflozin arm of CANVAS”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR; CANVAS Program Collaborative Group. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017; 377: 644– 657. doi: 10.1056/NEJMoa1611925 28605608 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In PROMISE, there was a significant interaction by diabetes mellitus (P=0.02); patients with diabetes mellitus randomized to CTA had a lower risk of cardiovascular death or nonfatal myocardial infarction compared with those randomized to functional stress testing (1.1% versus 2.6%; adjusted HR, 0.38 [95% CI, 0.18-0.79]; P=0.01).

    “there was a significant interaction by diabetes mellitus (P=0.02); patients with diabetes mellitus who were randomized to CTA had a lower risk of cardiovascular death or nonfatal myocardial infarction compared with those randomized to functional stress testing (1.1% versus 2.6%; adjusted HR, 0.38 [95% CI, 0.18–0.79]; P=0.01)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [232] Sharma A, Coles A, Sekaran NK, Pagidipati NJ, Lu MT, Mark DB, Lee KL, Al-Khalidi HR, Hoffmann U, Douglas PS. Stress testing versus CT angiography in patients with diabetes and suspected coronary artery disease. J Am Coll Cardiol. 2019; 73: 893– 902. doi: 10.1016/j.jacc.2018.11.056 30819356 PMC7101508 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The SCOT-HEART trial was an open-label randomized comparison of coronary computed tomography angiography with standard care in 4146 subjects with stable chest pain (444 with diabetes mellitus) from 2010 to 2014.

    “The SCOT-HEART trial (Scottish Computed Tomography of the Heart) was an open-label randomized comparison of CTA with standard care (which could include stress testing, angiography, or continued medical management) in 4146 subjects with stable chest pain (444 with diabetes mellitus) from 2010 to 2014.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [230] SCOT-HEART Investigators, Newby DE, Adamson PD, Berry C, Boon NA, Dweck MR, Flather M, Forbes J, Hunter A, Lewis S, MacLean S, Coronary CT angiography and 5-year risk of myocardial infarction. N Engl J Med. 2018; 379: 924– 933. doi: 10.1056/NEJMoa1805971 30145934 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Increasing burden of chronic angina is associated with increased hospitalizations and healthcare costs.

    “but also is associated with increased hospitalizations and healthcare costs”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [236] Arnold SV, Morrow DA, Lei Y, Cohen DJ, Mahoney EM, Braunwald E, Chan PS. Economic impact of angina after an acute coronary syndrome: insights from the MERLIN-TIMI 36 trial. Circ Cardiovasc Qual Outcomes. 2009; 2: 344– 353. doi: 10.1161/CIRCOUTCOMES.108.829523 20031860 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    PROMISE randomly assigned 8966 patients with stable chest pain (1908 with diabetes mellitus) to either CTA or functional testing and showed no difference in outcomes over a median of 2 years of follow-up.

    “PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain), which randomly assigned 8966 patients with stable chest pain (1908 with diabetes mellitus) to either CTA or functional testing and showed no difference in outcomes over a median of 2 years of follow-up.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [231] Douglas PS, Hoffmann U, Patel MR, Mark DB, Al-Khalidi HR, Cavanaugh B, Cole J, Dolor RJ, Fordyce CB, Huang M,; PROMISE Investigators. Outcomes of anatomical versus functional testing for coronary artery disease. N Engl J Med. 2015; 372: 1291– 1300. doi: 10.1056/NEJMoa1415516 25773919 PMC4473773 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    On the basis of these studies, it is now clear that although glucose lowering itself has at best only a modest impact on cardiovascular events, the method by which glucose is lowered may matter.

    “On the basis of these studies, it is now clear that although glucose lowering itself has, at best, only modest impact on cardiovascular events, the method by which glucose is lowered may.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Further analysis of PROMISE showed that a substantial proportion of myocardial infarctions occurred in patients with nonobstructive coronary artery disease identified by CTA, disease that would not be detected by functional testing and could prompt important changes in prevention strategies.

    “Further analysis showed that a substantial proportion of myocardial infarctions occurred in patients with nonobstructive CAD identified by CTA, disease that would not be detected by functional testing and could prompt important changes in prevention strategies.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [231] Douglas PS, Hoffmann U, Patel MR, Mark DB, Al-Khalidi HR, Cavanaugh B, Cole J, Dolor RJ, Fordyce CB, Huang M,; PROMISE Investigators. Outcomes of anatomical versus functional testing for coronary artery disease. N Engl J Med. 2015; 372: 1291– 1300. doi: 10.1056/NEJMoa1415516 25773919 PMC4473773 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    About one-third of patients with stable coronary artery disease report chronic angina.

    “about one-third of patients with stable CAD report chronic angina”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [233] Kureshi F, Shafiq A, Arnold SV, Gosch K, Breeding T, Kumar AS, Jones PG, Spertus JA. The prevalence and management of angina among patients with chronic coronary artery disease across US outpatient cardiology practices: insights from the Angina Prevalence and Provider Evaluation of Angina Relief (APPEAR) study. Clin Cardiol. 2017; 40: 6– 10. doi: 10.1002/clc.22628 28146269 PMC5300688 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In head-to-head trials, patients with type 2 diabetes treated with vasodilating versus nonvasodilating β-blockers had small but significant decreases in HbA1c levels (0.1%-0.2%), improved insulin sensitivity, lower cholesterol levels, less weight gain, and less progression to microalbuminuria.

    “In head-to-head trials, patients with T2DM who were treated with vasodilating (versus nonvasodilating) β-blockers had small but significant decreases in HbA1c levels (0.1%–0.2%), improved insulin sensitivity, lower cholesterol levels, less weight gain, and less progression to microalbuminuria.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [96] Bakris GL, Fonseca V, Katholi RE, McGill JB, Messerli FH, Phillips RA, Raskin P, Wright JT Jr, Oakes R, Lukas MA,; GEMINI Investigators. Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial. JAMA. 2004; 292: 2227– 2236. doi: 10.1001/jama.292.18.2227 15536109 source

      Not checked in the free run.

    • cites [254] Badar VA, Hiware SK, Shrivastava MP, Thawani VR, Hardas MM. Comparison of nebivolol and atenolol on blood pressure, blood sugar, and lipid profile in patients of essential hypertension. Indian J Pharmacol. 2011; 43: 437– 440. doi: 10.4103/0253-7613.83117 21845001 PMC3153709 source

      Not checked in the free run.

    • cites [255] Giugliano D, Acampora R, Marfella R, De Rosa N, Ziccardi P, Ragone R, De Angelis L, D’Onofrio F. Metabolic and cardiovascular effects of carvedilol and atenolol in non-insulin-dependent diabetes mellitus and hypertension: a randomized, controlled trial. Ann Intern Med. 1997; 126: 955– 959. doi: 10.7326/0003-4819-126-12-199706150-00004 9182472 source

      Not checked in the free run.

    • cites [256] Torp-Pedersen C, Metra M, Charlesworth A, Spark P, Lukas MA, Poole-Wilson PA, Swedberg K, Cleland JG, Di Lenarda A, Remme WJ,; COMET Investigators. Effects of metoprolol and carvedilol on preexisting and new onset diabetes in patients with chronic heart failure: data from the Carvedilol Or Metoprolol European Trial (COMET). Heart. 2007; 93: 968– 973. doi: 10.1136/hrt.2006.092379 17237130 PMC1994413 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In SUSTAIN 6 (n=3297), semaglutide produced a 26% relative risk reduction in major adverse cardiovascular events (6.6% versus 8.9%) but no reduction in cardiovascular mortality.

    “semaglutide produced a 26% RRR in MACEs (6.6% versus 8.9%) but no reduction in cardiovascular mortality”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [10] Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML,; SUSTAIN-6 Investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016; 375: 1834– 1844. doi: 10.1056/NEJMoa1607141 27633186 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Ranolazine reduces myocardial ischemia at the cellular level and is the only antianginal medication to be tested and found effective specifically in patients with type 2 diabetes.

    “Ranolazine reduces myocardial ischemia at the cellular level and is the only antianginal medication to be tested and found effective specifically in patients with T2DM.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [257] Kosiborod M, Arnold SV, Spertus JA, McGuire DK, Li Y, Yue P, Ben-Yehuda O, Katz A, Jones PG, Olmsted A, Evaluation of ranolazine in patients with type 2 diabetes mellitus and chronic stable angina: results from the TERISA randomized clinical trial (Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina). J Am Coll Cardiol. 2013; 61: 2038– 2045. doi: 10.1016/j.jacc.2013.02.011 23500237 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    β-Blockers reduce heart rate and myocardial contractility, but this can induce compensatory peripheral vasoconstriction, leading to increased insulin resistance and a more atherogenic lipid profile.

    “β-Blockers reduce heart rate and myocardial contractility (thereby reducing myocardial oxygen demand), but this can induce compensatory peripheral vasoconstriction, which leads to increased insulin resistance and a more atherogenic lipid profile.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [96] Bakris GL, Fonseca V, Katholi RE, McGill JB, Messerli FH, Phillips RA, Raskin P, Wright JT Jr, Oakes R, Lukas MA,; GEMINI Investigators. Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial. JAMA. 2004; 292: 2227– 2236. doi: 10.1001/jama.292.18.2227 15536109 source

      Not checked in the free run.

    • cites [97] Bangalore S, Parkar S, Grossman E, Messerli FH. A meta-analysis of 94,492 patients with hypertension treated with beta blockers to determine the risk of new-onset diabetes mellitus. Am J Cardiol. 2007; 100: 1254– 1262. doi: 10.1016/j.amjcard.2007.05.057 17920367 source

      Not checked in the free run.

    • cites [253] Dornhorst A, Powell SH, Pensky J. Aggravation by propranolol of hyperglycaemic effect of hydrochlorothiazide in type II diabetics without alteration of insulin secretion. Lancet. 1985; 1: 123– 126. doi: 10.1016/s0140-6736(85)91900-2 2857210 source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation

    In LEADER, liraglutide led to a 13% relative risk reduction in major adverse cardiovascular events (13.0% versus 14.9%) in 9340 patients with overt or at high risk for cardiovascular disease.

    “liraglutide led to a 13% RRR in MACEs (13.0% versus 14.9%)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, Nissen SE, Pocock S, Poulter NR, Ravn LS,; LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016; 375: 311– 322. doi: 10.1056/NEJMoa1603827 27295427 PMC4985288 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In SCOT-HEART, revascularization rates were similar in the two groups and probably did not play a major role in the difference in the primary end point.

    “Revascularization rates were similar in the 2 groups and probably did not play a major role in the difference between the groups in the rate of the primary end point.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [230] SCOT-HEART Investigators, Newby DE, Adamson PD, Berry C, Boon NA, Dweck MR, Flather M, Forbes J, Hunter A, Lewis S, MacLean S, Coronary CT angiography and 5-year risk of myocardial infarction. N Engl J Med. 2018; 379: 924– 933. doi: 10.1056/NEJMoa1805971 30145934 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Evidence suggests that more complete revascularization in bypassed territories explains the gradual increase in CABG benefit after 4 to 5 years, while incomplete PCI carries a corresponding hazard over that period.

    “suggest that the more complete revascularization that can be achieved in bypassed territories accounts for a gradual accrual of benefit beyond 4 to 5 years after CABG, whereas there is an accompanying hazard associated with incomplete PCI over this time course.275,276”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [275] Esper RB, Farkouh ME, Ribeiro EE, Hueb W, Domanski M, Hamza TH, Siami FS, Godoy LC, Mathew V, French J, SYNTAX score in patients with diabetes undergoing coronary revascularization in the FREEDOM trial. J Am Coll Cardiol. 2018; 72(pt A): 2826– 2837. doi: 10.1016/j.jacc.2018.09.046 30522646 source

      Not checked in the free run.

    • cites [276] Jiménez-Navarro MF, López-Jiménez F, Barsness G, Lennon RJ, Sandhu GS, Prasad A. Long-term prognosis of complete percutaneous coronary revascularisation in patients with diabetes with multivessel disease. Heart. 2015; 101: 1233– 1239. doi: 10.1136/heartjnl-2014-307143 25882502 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    In FREEDOM extended follow-up, survival curves separated after 2 years and continued to widen, indicating a durable long-term benefit.

    “with survival curves diverging beyond 2 years and continuing to widen throughout follow-up, suggesting a robust long-term benefit.293”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [293] Farkouh ME, Domanski M, Dangas GD, Godoy LC, Mack MJ, Siami FS, Hamza TH, Shah B, Stefanini GG, Sidhu MS,; FREEDOM Follow-On Study Investigators. Long-term survival following multivessel revascularization in patients with diabetes: the FREEDOM Follow-On Study. J Am Coll Cardiol. 2019; 73: 629– 638. doi: 10.1016/j.jacc.2018.11.001 30428398 PMC6839829 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    FREEDOM also found a small quality-of-life benefit favoring CABG from 6 months to 2 years, with no further gain after 2 years.

    “There was also a small favorable benefit in quality of life favoring CABG from 6 months to 2 years, although there was no further accrual of benefit beyond 2 years.294”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [294] Abdallah MS, Wang K, Magnuson EA, Spertus JA, Farkouh ME, Fuster V, Cohen DJ; FREEDOM Trial Investigators. Quality of life after PCI vs CABG among patients with diabetes and multivessel coronary artery disease: a randomized clinical trial. JAMA. 2013; 310: 1581– 1590. doi: 10.1001/jama.2013.279208 24129463 PMC4370776 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In type 2 diabetes, outcomes of both surgical and percutaneous revascularization are worse, with higher risks of procedural complications and long-term lesion formation, progression, and restenosis.

    “Both surgical and percutaneous revascularization outcomes are impaired in the setting of T2DM, with an increased risk of adverse procedural events and of long-term lesion development, progression, and restenosis.25,268,269”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [25] Barsness GW, Holmes DR Jr, Gersh BJ. Integrated management of patients with diabetes mellitus and ischemic heart disease: PCI, CABG, and medical therapy. Curr Probl Cardiol. 2005; 30: 583– 617. 16230183 source

      Not checked in the free run.

    • cites [268] Nicholls SJ, Tuzcu EM, Kalidindi S, Wolski K, Moon KW, Sipahi I, Schoenhagen P, Nissen SE. Effect of diabetes on progression of coronary atherosclerosis and arterial remodeling: a pooled analysis of 5 intravascular ultrasound trials. J Am Coll Cardiol. 2008; 52: 255– 262. doi: 10.1016/j.jacc.2008.03.051 18634979 source

      Not checked in the free run.

    • cites [269] Barsness GW, Gersh BJ, Brooks MM, Frye RL; BARI 2D Trial Investigators. Rationale for the revascularization arm of the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial. Am J Cardiol. 2006; 97: 31G– 40G. doi: 10.1016/j.amjcard.2006.03.011 16813736 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    For patients with multivessel disease, left main disease, or complex coronary anatomy, CABG is linked to fewer long-term major adverse cardiovascular events than PCI, though it carries a small early increase in stroke risk.

    “In patients with multivessel CAD, left main disease, and complex coronary anatomy, coronary artery bypass grafting (CABG) is associated with reduced long-term MACEs compared with PCI, albeit with a small increased early risk of stroke272,273”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [272] Head SJ, Milojevic M, Daemen J, Ahn JM, Boersma E, Christiansen EH, Domanski MJ, Farkouh ME, Flather M, Fuster V, Mortality after coronary artery bypass grafting versus percutaneous coronary intervention with stenting for coronary artery disease: a pooled analysis of individual patient data. Lancet. 2018; 391: 939– 948. doi: 10.1016/S0140-6736(18)30423-9 29478841 source

      Not checked in the free run.

    • cites [273] Bhatt DL. CABG the clear choice for patients with diabetes and multivessel disease. Lancet. 2018; 391: 913– 914. doi: 10.1016/S0140-6736(18)30424-0 29478842 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In BARI, patients with diabetes randomized to CABG had significantly better survival than those randomized to balloon angioplasty, with the difference continuing to grow through 10 years.

    “In this trial, significantly improved survival was noted in the subgroup of patients with diabetes mellitus who were randomized to CABG, a difference that continued to accrue out to 10 years from study entry.279”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [279] BARI Investigators. The final 10-year follow-up results from the BARI randomized trial. J Am Coll Cardiol. 2007; 49: 1600– 1606. doi: 10.1016/j.jacc.2006.11.048 17433949 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The 30-day stroke rate is 1.8% with CABG and 0.3% with PCI.

    “(30-day stroke rate for CABG versus PCI, 1.8% versus 0.3%274)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [274] Farkouh ME, Domanski M, Sleeper LA, Siami FS, Dangas G, Mack M, Yang M, Cohen DJ, Rosenberg Y, Solomon SD,; FREEDOM Trial Investigators. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med. 2012; 367: 2375– 2384. doi: 10.1056/NEJMoa1211585 23121323 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Because both percutaneous and surgical revascularization have worse outcomes in type 2 diabetes, primary and secondary medical prevention remains the foundation of care.

    “Because both percutaneous and surgical revascularization outcomes are impaired in the presence of T2DM, primary and secondary medical preventive therapy remains the foundation of care.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Pooled retrospective data suggest that skeletonized bilateral internal mammary artery harvesting is safe and may improve long-term survival.

    “Although pooled analysis from retrospective studies suggests the safety of skeletonized bilateral IMA harvest285,286 and the potential for superior long-term survival associated with this approach,284”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [285] Deo SV, Shah IK, Dunlay SM, Erwin PJ, Locker C, Altarabsheh SE, Boilson BA, Park SJ, Joyce LD. Bilateral internal thoracic artery harvest and deep sternal wound infection in diabetic patients. Ann Thorac Surg. 2013; 95: 862– 869. doi: 10.1016/j.athoracsur.2012.11.068 23352296 source

      Not checked in the free run.

    • cites [286] Weiss AJ, Zhao S, Tian DH, Taggart DP, Yan TD. A meta-analysis comparing bilateral internal mammary artery with left internal mammary artery for coronary artery bypass grafting. Ann Cardiothorac Surg. 2013; 2: 390– 400. doi: 10.3978/j.issn.2225-319X.2013.07.16 23977614 PMC3741881 source

      Not checked in the free run.

    • cites [284] Kajimoto K, Yamamoto T, Amano A. Coronary artery bypass revascularization using bilateral internal thoracic arteries in diabetic patients: a systematic review and meta-analysis. Ann Thorac Surg. 2015; 99: 1097– 1104. doi: 10.1016/j.athoracsur.2014.09.045 25620592 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Much of the long-term advantage of CABG over balloon angioplasty came from a durable conduit that bypassed the entire proximal vessel, producing an early survival benefit after myocardial infarction in patients who received left internal mammary artery grafts.

    “Much of the observed long-term benefit of CABG over balloon angioplasty was attributable to a durable surgical conduit bypassing the entire proximal vessel, resulting in a documented early survival advantage after myocardial infarction in patients treated with left internal mammary artery (IMA) grafts.280”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [280] Detre KM, Lombardero MS, Brooks MM, Hardison RM, Holubkov R, Sopko G, Frye RL, Chaitman BR. The effect of previous coronary-artery bypass surgery on the prognosis of patients with diabetes who have acute myocardial infarction: Bypass Angioplasty Revascularization Investigation Investigators. N Engl J Med. 2000; 342: 989– 997. doi: 10.1056/NEJM200004063421401 10749960 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Both the antianginal effect and the glucose-lowering effect of ranolazine appear to be enhanced in patients with poorly controlled type 2 diabetes.

    “Both the antianginal effect259 and the glucose-lowering effect260–262 of ranolazine appear to be enhanced in patients with poorly controlled T2DM.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [259] Arnold SV, McGuire DK, Spertus JA, Li Y, Yue P, Ben-Yehuda O, Belardinelli L, Jones PG, Olmsted A, Chaitman BR, Effectiveness of ranolazine in patients with type 2 diabetes mellitus and chronic stable angina according to baseline hemoglobin A1c. Am Heart J. 2014; 168: 457– 465.e2. 25262254 source

      Not checked in the free run.

    • cites [260] Timmis AD, Chaitman BR, Crager M. Effects of ranolazine on exercise tolerance and HbA1c in patients with chronic angina and diabetes. Eur Heart J. 2006; 27: 42– 48. doi: 10.1093/eurheartj/ehi495 16176940 source

      Not checked in the free run.

    • cites [261] Morrow DA, Scirica BM, Chaitman BR, McGuire DK, Murphy SA, Karwatowska-Prokopczuk E, McCabe CH, Braunwald E; MERLIN-TIMI 36 Investigators. Evaluation of the glycometabolic effects of ranolazine in patients with and without diabetes mellitus in the MERLIN-TIMI 36 randomized controlled trial. Circulation. 2009; 119: 2032– 2039. doi: 10.1161/CIRCULATIONAHA.107.763912 19349325 source

      Not checked in the free run.

    • cites [262] Chisholm JW, Goldfine AB, Dhalla AK, Braunwald E, Morrow DA, Karwatowska-Prokopczuk E, Belardinelli L. Effect of ranolazine on A1C and glucose levels in hyperglycemic patients with non-ST elevation acute coronary syndrome. Diabetes Care. 2010; 33: 1163– 1168. doi: 10.2337/dc09-2334 20357382 PMC2875416 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    This consistent effect has been seen in later contemporary revascularization trials and in pooled analysis.

    “A consistent effect has been identified throughout subsequent contemporary revascularization trials,266 including in pooled analysis.281”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [266] Chaitman BR, Hardison RM, Adler D, Gebhart S, Grogan M, Ocampo S, Sopko G, Ramires JA, Schneider D, Frye RL; Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Study Group. The Bypass Angioplasty Revascularization Investigation 2 Diabetes randomized trial of different treatment strategies in type 2 diabetes mellitus with stable ischemic heart disease: impact of treatment strategy on cardiac mortality and myocardial infarction. Circulation. 2009; 120: 2529– 2540. doi: 10.1161/CIRCULATIONAHA.109.913111 19920001 PMC2830563 source

      Not checked in the free run.

    • cites [281] Doenst T, Haverich A, Serruys P, Bonow RO, Kappetein P, Falk V, Velazquez E, Diegeler A, Sigusch H. PCI and CABG for treating stable coronary artery disease: JACC review topic of the week. J Am Coll Cardiol. 2019; 73: 964– 976. doi: 10.1016/j.jacc.2018.11.053 30819365 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    CABG with optimized medical therapy is expected to improve outcomes for most patients with type 2 diabetes and multivessel coronary disease and is the revascularization strategy recommended by current US and European guidelines.

    “with the understanding that CABG with OMT will offer improved outcomes in the majority of patients with T2DM and multivessel CAD and is the revascularization strategy recommended by current US and European society guidelines.229,298”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [229] Fihn SD, Blankenship JC, Alexander KP, Bittl JA, Byrne JG, Fletcher BJ, Fonarow GC, Lange RA, Levine GN, Maddox TM, 2014 ACC/AHA/AATS/PCNA/SCAI/STS focused update of the guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, and the American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2014; 130: 1749– 1767. doi: source

      Not checked in the free run.

    • cites [298] Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, Byrne RA, Collet JP, Falk V, Head SJ,; ESC Scientific Document Group. 2018 ESC/EACTS guidelines on myocardial revascularization. Eur Heart J. 2019; 40: 87– 165. doi: 10.1093/eurheartj/ehy394 30165437 source

      Not checked in the free run.

86 of 86

  • The paper relies on this without support.

    Failure to adopt guideline-based recommendations is a major underlying cause of care gaps.

    “Although the cost of medications and patient adherence are important considerations that predispose to these gaps, failure to adopt guideline-based recommendations remains a major underlying factor.”

  • The paper relies on this without support.

    Many patients with type 2 diabetes and coronary disease cannot tolerate intensive statins or do not reach adequate LDL cholesterol lowering with maximally tolerated statins and therefore need other lipid-lowering therapies.

    “Despite their key role in secondary prevention in patients with T2DM and CAD, many patients are unable to tolerate intensive statins because of side effects or do not achieve adequate LDL-C lowering with maximally tolerated statins and need alternative lipid-lowering therapies for secondary prevention.”

  • The paper relies on this without support.

    Beta-blockers reduce myocardial oxygen demand and are often regarded as part of optimal medical therapy for all patients with coronary artery disease.

    “β-Blockers reduce myocardial oxygen demand and are often considered a part of optimal medical therapy (OMT) for all patients with CAD.”

  • The paper relies on this without support.

    Many patients with coronary artery disease have indications for beta-blockers beyond blood pressure reduction.

    “However, many patients with CAD have indications for β-blockers other than just blood pressure reduction.”

  • The paper relies on this without support.

    Smoking cessation can cause weight gain, which can be especially problematic in type 2 diabetes patients who already have obesity and insulin resistance.

    “Smoking cessation can be associated with weight gain, which can be particularly problematic in patients with T2DM who may already struggle with obesity and associated insulin resistance.”

  • The paper relies on this without support.

    Thiazolidinediones increase the risk of heart failure because of sodium retention at the distal nephron, and this risk is greater at higher doses and when used with insulin.

    “thiazolidinediones unfortunately also increase the risk of heart failure as a result of their sodium retentive properties at the distal nephron, and this risk is accentuated at higher doses and when the drugs are used with insulin”

  • The paper relies on this without support.

    Randomized controlled trials of bariatric surgery have been inadequately powered to assess cardiovascular events and mortality.

    “randomized controlled trials have thus far been inadequately powered to assess cardiovascular events and mortality”

  • The paper relies on this without support.

    Studies designed to answer clinical questions about the management of stable coronary artery disease in type 2 diabetes are lacking.

    “studies designed to answer clinical questions about the management of stable CAD in T2DM are lacking”

  • The paper relies on this without support.

    Patients with type 2 diabetes have at least as high a burden of angina as those without type 2 diabetes.

    “understanding that patients with T2DM have at least as high a burden of angina as those without T2DM”

  • The paper relies on this without support.

    DPP4 inhibitors are somewhat less powerful than traditional glucose-lowering agents but do not cause hypoglycemia or weight gain and are generally well tolerated.

    “These medications are somewhat less powerful than traditional agents but do not result in any hypoglycemia or weight gain and are generally well tolerated.”

  • The paper relies on this without support.

    SGLT2 inhibitors reduce blood glucose by increasing glucosuria and are associated with modest reductions in body weight and blood pressure.

    “These oral agents reduce blood glucose by increasing glucosuria and are associated with modest reductions in body weight and blood pressure.”

  • The paper relies on this without support.

    GLP-1 receptor agonists have a stronger effect on HbA1c and weight loss than either DPP4 inhibitors or SGLT2 inhibitors.

    “Their use is associated with a stronger effect on HbA1c and weight loss than either DPP4 inhibitors or SGLT2 inhibitors.”

  • The paper relies on this without support.

    GLP-1 receptor agonist side effects include nausea and vomiting and possibly an increase in gallbladder disease.

    “Side effects include nausea and vomiting and possibly an increase in gallbladder disease.”

  • The paper relies on this without support.

    Diabetes mellitus causes widespread vascular dysfunction that raises cardiovascular risk.

    “Diabetes mellitus is associated with marked and widespread vascular perturbation leading to enhanced cardiovascular risk.”
14 of 14

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • ACE inhibitors or ARB therapy have well-established long-term benefit in people with diabetes and CKD or hypertension.

    “ACE inhibitors or ARB therapy also have well-established long-term benefit in people with diabetes and CKD or hypertension, and these agents are recommended for hypertension management in people with known ASCVD (particularly coronary artery disease) (72,73,246).”

    From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [72]

    The Blood Pressure Control section recommends ACE inhibitors or ARBs for hypertension in patients with type 2 diabetes and coronary artery disease, and reports reduced kidney-disease progression in patients with albuminuria. It also describes cardiovascular benefit over 4.5 years. The claim extends these benefits to people with diabetes and CKD or hypertension generally, without the source’s albuminuria and coronary-disease qualifications. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • ACE inhibitors or ARB therapy have well-established long-term benefit in people with diabetes and CKD or hypertension.

    “ACE inhibitors or ARB therapy also have well-established long-term benefit in people with diabetes and CKD or hypertension, and these agents are recommended for hypertension management in people with known ASCVD (particularly coronary artery disease) (66,67,238).”

    From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [66]

    In Blood Pressure Control (page unavailable), the statement recommends ACE inhibitors or ARBs for hypertension in patients with type 2 diabetes and coronary artery disease, and reports renal benefit in patients with albuminuria. It also describes cardiovascular benefits over 4.5 years in a diabetes trial. The claim extends the kidney benefit to people with diabetes and CKD generally, whereas the passage specifies albuminuria. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • In patients with diabetes and multivessel disease, CABG with arterial grafts is preferred over complex PCI, providing that patient characteristics are considered.

    “In brief, given the current knowledge, in patients with diabetes and multivessel disease, CABG with arterial grafts is preferred over complex PCI, providing that patient characteristics (e.g.frailty, cerebrovascular disease) are considered.398”

    From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [398]

  • Because most trials on revascularization contained patients with T2DM, current Guidelines cannot easily be applied to patients with T1DM.

    “Because most of the trials on revascularization contained patients with T2DM, current Guidelines cannot easily be applied to patients with T1DM.”

    From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [398]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Survival rates run opposite to the stated CABG advantage

    Minor

    The sentence says CABG has a survival advantage over PCI, but its CABG-versus-PCI ordering assigns CABG 84.5% survival and PCI 90.0%. Those rates instead favor PCI.

1 of 1

Cites

1 retracted

Flagged first, then by citations

Research works printed but not linked: 4

  1. 10.1001/jama.2019.347 · DOI
  2. 10.1161/circinterventions.110.96018 · DOI
  3. 10.1161/circ.97.22.2202 · DOI
  4. 10.1016/s0140-6736(08)60104-x · DOI · Paper page

Cited by

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Related

Authors
Arnold, S. V., Bhatt, D. L., Barsness, G. W., Beatty, A. L., Deedwania, P. C., Inzucchi, S. E., Kosiborod, M., Leiter, L. A., Lipska, K. J., Newman, J. D., Welty, F. K., & On behalf of the American Heart Association Council on Lifestyle and Cardiometabolic Health and Council on Clinical Cardiology
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2020-05-12
Volume
141
Issue
19
Pages
e779-e806
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/cir.0000000000000766
PMC
PMC12204403
OpenAlex
W3015405225
Cited by
304
References
297
Citations by year
2026: 34 · 2025: 49 · 2024: 53 · 2023: 57 · 2022: 49 · 2021: 47 · 2020: 15
FWCI
31.68
Type
journal article
Language
en
Open access
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Heart, Lung, and Blood Institute (K23HL125991)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Surgery › Coronary Interventions and Diagnostics
Keywords
stable coronary artery disease, type 2 diabetes, secondary prevention, stable angina, revascularization strategy, glycemic control, glucose-lowering medications, cardiovascular risk, cardiovascular outcomes
MeSH terms
Clinical Decision-Making, American Heart Association, Coronary Artery Disease, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Myocardial Revascularization, Risk Factors, United States, Comorbidity, Treatment Outcome, Risk Assessment, Patient-Centered Care, Consensus, Risk Reduction Behavior, Secondary Prevention

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-04.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-04.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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