10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025

In the paper

“In addition, the CAROLINA (Cardiovascular Outcome Study of Linagliptin Versus Glimepiride in Type 2 Diabetes) study demonstrated noninferiority between a DPP-4 inhibitor, linagliptin, and a sulfonylurea, glimepiride, on cardiovascular outcomes despite lower rates of hypoglycemia in the linagliptin treatment group (254).”

What the sources say

• Disputed

  The Discussion describes CAROLINA as an ongoing trial designed to test cardiovascular noninferiority, not one that had demonstrated it. It attributes the lower hypoglycemia incidence to a former study, not to results from CAROLINA. (LLM, conf=0.91)

  Checked by a reasoning model — may be wrong.

  cites [254] Marx, 2015, Design and baseline characteristics of the CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes (CAROLINA), Diab Vasc Dis Res sourceExperimental — accuracy not yet measured

In the paper

“Randomized clinical trials have demonstrated unequivocally that treatment of hypertension reduces cardiovascular events as well as microvascular complications (31)(32)(33)(34)(35)(36)(37).”

What the sources say

• ?Not checked — no full text of the sourcecites [31] Emdin, 2015, Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis, JAMA source
• Partly supported

  The Background (page not specified) says trials have shown a cardiovascular benefit from antihypertensive drugs, and the review reports a reduction in stroke with a lower systolic blood-pressure target. But the Discussion (page not specified) says intensive blood-pressure lowering did not show a significant benefit for microvascular events over standard control. This source therefore does not support the claim that trials unequivocally demonstrated reductions in both kinds of complication. (LLM, conf=0.84)

  cites [32] Arguedas, 2013, Blood pressure targets for hypertension in people with diabetes mellitus, Cochrane Database Syst Rev sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [33] Ettehad, 2016, Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis, Lancet source

In the paper

“Furthermore, large benefits are seen when multiple cardiovascular risk factors (glycemic, blood pressure, and lipid management) are addressed simultaneously, with evidence for long-lasting benefits (3)(4)(5).”

What the sources say

• Supported

  The Discussion (page not available) describes the risk reductions as high compared with single-risk-factor trials and says concomitant treatment of multiple risk factors is important; it discusses glycaemic, blood-pressure and lipid control. The Results (page not available) report a 51% relative reduction in incident cardiovascular disease and a mortality benefit that persisted during long-term follow-up. These findings support the claim for the studied patients with type 2 diabetes and microalbuminuria. (LLM, conf=0.91)

  cites [3] Gæde, 2016, Years of life gained by multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: 21 years follow-up on the Steno-2 randomised trial, Diabetologia source
• Supported

  The Results report that intensive therapy improved glycemic, blood-pressure, and lipid measures compared with conventional therapy. Over 13.3 years, the intensive-therapy group had a 29% absolute reduction in cardiovascular-event risk, with no evidence that the benefit changed after the formal intervention ended (Results, p. 586). (LLM, conf=0.92)

  cites [4] Gaede, 2008, Effect of a multifactorial intervention on mortality in type 2 diabetes, N Engl J Med source
• ?Not checked — no full text of the sourcecites [5] Khunti, 2018, Legacy benefits of blood glucose, blood pressure and lipid control in individuals with diabetes and cardiovascular disease: time to overcome multifactorial therapeutic inertia?, Diabetes Obes Metab source

In the paper

“The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that treatment to a goal systolic blood pressure of <120 mmHg decreases cardiovascular event rates by 25% in high-risk individuals, although people with diabetes were excluded from this trial (38).”

What the sources say

• Supported

  The Discussion reports a 25% lower relative risk of the primary cardiovascular outcome with a systolic blood-pressure target below 120 mm Hg versus below 140 mm Hg. It specifies that participants had hypertension without diabetes; the conclusion describes them as at high risk for cardiovascular events. (LLM, conf=0.94)

  cites [38] Wright, 2015, A randomized trial of intensive versus standard blood-pressure control, N Engl J Med source

In the paper

“The results have been interpreted to be generally consistent between the two trials, but ACCORD BP was viewed as underpowered due to the composite primary end point being less sensitive to blood pressure regulation (38,40).”

What the sources say

• Partly supported

  The Discussion (page unavailable in our copy) says ACCORD BP’s nonsignificant cardiovascular result was consistent with the benefit observed in SPRINT and notes that ACCORD had about half SPRINT’s sample size. It does not say ACCORD was viewed as underpowered because its composite primary end point was less sensitive to blood-pressure regulation. (LLM, conf=0.88)

  cites [38] Wright, 2015, A randomized trial of intensive versus standard blood-pressure control, N Engl J Med sourceExperimental — accuracy not yet measured
• Partly supported

  The Discussion (page not available in our copy) says ACCORD BP had reduced power because the observed event rate was almost 50% lower than expected. The Methods identify a composite primary outcome, but the paper does not attribute reduced power to that outcome being less sensitive to blood-pressure control or compare ACCORD BP with SPRINT. (LLM, conf=0.88)

  cites [40] Cushman, 2010, Effects of intensive blood-pressure control in type 2 diabetes mellitus, N Engl J Med sourceExperimental — accuracy not yet measured

In the paper

“Diabetes is also an important risk factor for incident heart failure, which is at least twofold more prevalent in people with diabetes compared with those without diabetes and is a major cause of morbidity and mortality (11).”

What the sources say

• Partly supported

  The Results section (page unavailable) reports a pooled risk ratio of 2.14 for new-onset heart failure in people with diabetes versus those without, supporting the incident-risk claim. That measures risk, not how prevalent heart failure is in the two groups. The Introduction describes heart failure as a major clinical and public-health problem, but the passages do not establish the claim about mortality. (LLM, conf=0.85)

  cites [11] Kodama, 2020, Diabetes mellitus and risk of new-onset and recurrent heart failure: a systematic review and meta-analysis, ESC Heart Fail sourceExperimental — accuracy not yet measured

In the paper

“These three comorbidities are frequently caused by metabolic risk, which is frequently driven by obesity and its associated risk factors, and the incidence of all three conditions rises with increasing A1C levels (17).”

What the sources say

• Partly supported

  The Results (Incident Disease Outcomes; page unavailable) show that risk of ASCVD, CKD, and heart failure generally increased across HbA1c levels, though the thresholds for significantly increased adjusted risk differed by condition. The Results (Study Cohort; page unavailable) also report higher BMI and other cardiometabolic risk factors in participants with prediabetes or T2D. These associations do not establish that metabolic risk frequently causes the three conditions or that obesity drives that risk. (LLM, conf=0.88)

  cites [17] Honigberg, 2021, Cardiovascular and kidney outcomes across the glycemic spectrum: insights from the UK Biobank, J Am Coll Cardiol sourceExperimental — accuracy not yet measured

In the paper

“Despite these encouraging opportunities to reduce morbidity and mortality, cardiovascular risk factors are predicted to increase and only a minority of people with type 2 diabetes achieve recommended risk factor goals and are treated with guideline-recommended therapy (7)(8)(9).”

What the sources say

• Partly supported

  The Results (CV Risk Factors; page not provided) project increases in several cardiovascular risk factors in the U.S. through 2060. The paper does not report what proportion of people with type 2 diabetes meet recommended risk-factor goals or receive guideline-recommended therapy. (LLM, conf=0.88)

  cites [7] Mohebi, 2022, Cardiovascular disease projections in the United States based on the 2020 Census estimates, J Am Coll Cardiol sourceExperimental — accuracy not yet measured
• Partly supported

  The Results and Discussion report that only 23% of US adults with diagnosed diabetes met the composite risk-factor goal in 2013–2016. The paper did not distinguish type 1 from type 2 diabetes, did not predict that cardiovascular risk factors would increase, and did not establish that only a minority received guideline-recommended therapy; its Discussion reports statin use in six in ten adults with diagnosed diabetes. Page numbers are unavailable in our copy. (LLM, conf=0.87)

  cites [8] Kazemian, 2019, Evaluation of the cascade of diabetes care in the United States, 2005–2016, JAMA Intern Med sourceExperimental — accuracy not yet measured
• Partly supported

  The Discussion and Conclusions report that fewer than 1 in 20 US patients with type 2 diabetes and ASCVD received all three evidence-based therapies, supporting the claim about limited use of recommended treatment in that population. The paper does not report that cardiovascular risk factors are predicted to increase or establish how many patients achieve recommended risk-factor goals; its cohort also does not represent all people with type 2 diabetes. No page numbers are available in our copy. (LLM, conf=0.88)

  cites [9] Nelson, 2022, Use of lipid-, blood pressure-, and glucose-lowering pharmacotherapy in patients with type 2 diabetes and atherosclerotic cardiovascular disease, JAMA Netw Open sourceExperimental — accuracy not yet measured

In the paper

“Diabetes itself confers independent ASCVD risk, and among people with diabetes, all major cardiovascular risk factors, including hypertension, hyperlipidemia, and obesity, are clustered and common (2).”

What the sources say

• Partly supported

  The Results (Study population; Table 3, page unavailable) show that hypertension and dyslipidemia were common among patients with type 2 diabetes, and the Abstract Results report that 45.2% had established ASCVD. The cited passages do not establish that diabetes independently confers ASCVD risk, or report obesity or the joint clustering of all three risk factors. (LLM, conf=0.88)

  cites [2] Weng, 2019, The prevalence of cardiovascular disease and antidiabetes treatment characteristics among a large type 2 diabetes population in the United States, Endocrinol Diabetes Metab sourceExperimental — accuracy not yet measured

In the paper

“Antihypertensive drugs known to be effective and safe in pregnancy include methyldopa, labetalol, and longacting nifedipine, while hydralazine may be considered in the acute management of hypertension in pregnancy or severe preeclampsia (56).”

What the sources say

• Partly supported

  The Antihypertensive medications section identifies labetalol and methyldopa as accepted first-line drugs and reports comparable safety and efficacy for hydralazine, labetalol, and nifedipine in acute severe hypertension during pregnancy. It does not establish the unqualified claim that all three listed drugs, specifically including long-acting nifedipine, are known to be safe throughout pregnancy: it notes limited and conflicting fetal-safety data and says not all societies support nifedipine as initial therapy. (LLM, conf=0.86)

  cites [56] Garovic, 2022, Hypertension in pregnancy: diagnosis, blood pressure goals, and pharmacotherapy: a scientific statement from the American Heart Association, Hypertension sourceExperimental — accuracy not yet measured

In the paper

“Treatment with ACE inhibitors and ARBs or MRAs can cause AKI and hyperkalemia, while diuretics can cause AKI and either hypokalemia or hyperkalemia (depending on mechanism of action) (84,85).”

What the sources say

• Partly supported

  The Discussion (p. 6) associates ACE inhibitors, ARBs, MRAs and potassium-sparing diuretics with hyperkalemia risk; the Results (p. 5) associate loop/thiazide diuretics with hypokalemia. The paper does not establish that these drugs cause the potassium changes—it says its observational analysis cannot disentangle medication risk from comorbidities—and the passages do not address AKI. (LLM, conf=0.88)

  cites [84] Nilsson, 2017, Incidence and determinants of hyperkalemia and hypokalemia in a large healthcare system, Int J Cardiol sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction (page unavailable) identifies hyperkalemia as an adverse event associated with ACE inhibitors and ARBs. The Results (page unavailable) also identify potassium-sparing diuretics as a risk factor for hyperkalemia after ACE inhibitor or ARB initiation. The passages do not establish the claim about MRAs, AKI from these drug classes, or diuretic-induced hypokalemia or AKI. (LLM, conf=0.86)

  cites [85] Bandak, 2017, Hyperkalemia after initiating renin-angiotensin system blockade: the Stockholm Creatinine Measurements (SCREAM) project, J Am Heart Assoc sourceExperimental — accuracy not yet measured

In the paper

“In CHIPS, aiming for a diastolic blood pressure of 85 mmHg during pregnancy was associated with reduced likelihood of developing accelerated maternal hypertension and no demonstrable adverse outcome for infants compared with aiming for a higher diastolic blood pressure.”

What the sources say

• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [53] Magee, 2015, Less-tight versus tight control of hypertension in pregnancy, N Engl J Med source

In the paper

“Among trials with lower baseline or attained blood pressure, antihypertensive treatment reduced the risk of stroke, retinopathy, and albuminuria, but effects on other ASCVD outcomes and heart failure were not evident.”

What the sources say

• ?Not checked — no full text of the sourcecites [20] Whelton, 2018, 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, J Am Coll Cardiol source
• ?Not checked — no full text of the sourcecites [31] Emdin, 2015, Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis, JAMA source
• Partly supported

  The Background (Main results) reports a reduced stroke incidence with a lower systolic BP target, while finding no difference in myocardial infarction or congestive heart failure with lower diastolic BP targets. The copy lists retinopathy and urinary albumin excretion as outcomes of included trials but does not report reductions in either. The Discussion also cautions against interpreting outcomes by attained BP rather than assigned treatment target. (LLM, conf=0.88)

  cites [32] Arguedas, 2013, Blood pressure targets for hypertension in people with diabetes mellitus, Cochrane Database Syst Rev sourceExperimental — accuracy not yet measured

In the paper

“Although prior analyses of randomized clinical trials found a benefit to evening versus morning dosing of antihypertensive medications (81,82), these results have not been reproduced in subsequent trials.”

What the sources say

• ?Not matched

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

  cites [81] Wu, 2011, Evening versus morning dosing regimen drug therapy for hypertension, Cochrane Database Syst Rev
• Supported

  The citation is attached to the finding of a benefit from evening versus morning dosing, not to the statement about subsequent trials. The Study design section describes a randomized comparison in patients with type 2 diabetes, and the Abstract Results report significantly lower cardiovascular risk when at least one medication was taken at bedtime rather than all medications upon awakening. (LLM, conf=0.91)

  cites [82] Hermida, 2011, Influence of time of day of blood pressure-lowering treatment on cardiovascular risk in hypertensive patients with type 2 diabetes, Diabetes Care source
• Partly supported

  The Discussion (page unavailable) reports earlier benefits from bedtime dosing, while this trial found no statistically significant reduction in nocturnal blood pressure with PM versus morning dosing. That supports a failure to reproduce a benefit in this trial, but the paper does not establish that subsequent trials generally failed to reproduce earlier results; its findings are limited to African Americans with hypertensive chronic kidney disease. (LLM, conf=0.84)

  cites [83] Rahman, 2013, A trial of 2 strategies to reduce nocturnal blood pressure in blacks with chronic kidney disease, Hypertension sourceExperimental — accuracy not yet measured

In the paper

“For individuals with blood pressure $150/90 mmHg, initial pharmacologic treatment with two antihypertensive medications is recommended to more effectively achieve blood pressure goals (63-65).”

What the sources say

• Partly supported

  The Discussion supports initial two-drug, fixed-dose therapy as a first-line strategy for high-risk patients with lower blood-pressure goals, and the Abstract reports better goal achievement than with initial monotherapy. The study concerns patients with type 2 diabetes; it does not establish a recommendation for all individuals at 150/90 mmHg or identify that reading as a treatment threshold. Page numbers were not available in our copy. (LLM, conf=0.87)

  cites [63] Bakris, 2003, Achieving goal blood pressure in patients with type 2 diabetes: conventional versus fixed-dose combination approaches, J Clin Hypertens (Greenwich) sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [64] Feldman, 2009, A simplified approach to the treatment of uncomplicated hypertension: a cluster randomized, controlled trial, Hypertension source
• Partly supported

  The Discussion reports that starting with two-drug therapy improved blood-pressure control compared with monotherapy in previous trials. It does not recommend two drugs specifically for people with blood pressure of 150/90 mm Hg; this trial tested an initial three-drug pill against usual care. (LLM, conf=0.85)

  cites [65] Webster, 2018, Fixed low-dose triple combination antihypertensive medication vs usual care for blood pressure control in patients with mild to moderate hypertension in Sri Lanka: a randomized clinical trial, JAMA sourceExperimental — accuracy not yet measured

In the paper

“Initial treatment for hypertension should include any of the drug classes demonstrated to reduce cardiovascular events in people with diabetes (25): ACE inhibitors (67,68), ARBs (67,68), thiazide-like diuretics (69), or dihydropyridine calcium channel blockers (70).”

What the sources say

• ?Not checked — no full text of the sourcecites [25] Mancia, 2023, 2023 ESH guidelines for the management of arterial hypertension The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension: endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA), J Hypertens source
• Partly supported

  The Results (Findings from Network Meta-Analysis; page not provided) report that ACE inhibitors significantly reduced major cardiovascular outcomes versus placebo in adults with diabetes. The Discussion reports generally similar cardiovascular effects for ACE inhibitors and ARBs and describes them as preferred therapies. The paper does not establish that thiazide-like diuretics or dihydropyridine calcium channel blockers reduce cardiovascular events, or recommend any of the four classes as initial treatment; those specific classes have separate citations in the citing sentence. (LLM, conf=0.86)

  cites [67] Catalá-López, 2016, Cardiovascular and renal outcomes of renin-angiotensin system blockade in adult patients with diabetes mellitus: a systematic review with network meta-analyses, PLoS Med sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [68] Palmer, 2015, Comparative efficacy and safety of blood pressure-lowering agents in adults with diabetes and kidney disease: a network meta-analysis, Lancet source

In the paper

“A 2018 Cochrane systematic review of antihypertensive therapy for mild to moderate chronic hypertension included 63 trials and over 5,909 women and suggested that antihypertensive therapy probably reduces the risk of developing severe hypertension but may not affect the risk of fetal or neonatal death, small-for-gestational-age babies, or preterm birth (52).”

What the sources say

• Partly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [52] Abalos, 2018, Antihypertensive drug therapy for mild to moderate hypertension during pregnancy, Cochrane Database Syst Rev sourceExperimental — accuracy not yet measured

In the paper

“In the absence of albuminuria, risk of progressive kidney disease is low, and ACE inhibitors and ARBs have not been found to afford superior cardioprotection compared with thiazide-like diuretics or dihydropyridine calcium channel blockers (75).”

What the sources say

• Partly supported

  The Results (Outcomes; page unavailable) find no general cardiovascular advantage for RAS blockers over thiazide diuretics or calcium channel blockers, although they report a lower risk of heart failure versus calcium channel blockers. The Discussion describes the study population as largely without albuminuria and finds no superiority for cardiovascular or renal outcomes. It does not establish that the risk of progressive kidney disease is low in the absence of albuminuria, or specifically analyze the thiazide-like and dihydropyridine subclasses named in the claim. (LLM, conf=0.86)

  cites [75] Bangalore, 2016, Diabetes mellitus as a compelling indication for use of renin angiotensin system blockers: systematic review and meta-analysis of randomized trials, BMJ sourceExperimental — accuracy not yet measured

In the paper

“Fewer musculoskeletal adverse effects occurred in those treated with evolocumab or ezetimibe than in those treated with ezetimibe plus placebo, although rates of discontinuation due to these effects were similar.”

What the sources say

• ?Not checked — no full text of the sourcecites [135] Sullivan, 2012, Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: the GAUSS randomized trial, JAMA source
• Partly supported

  The Abstract reports fewer muscle adverse events with evolocumab than with ezetimibe (12% versus 23%), and the OTHER LIPIDS safety passage reports similar discontinuation rates due to musculoskeletal effects (5% versus 6%); page numbers are unavailable in our copy. But the Methods describe evolocumab plus oral placebo versus ezetimibe plus injected placebo, not evolocumab or ezetimibe versus ezetimibe plus placebo. The claim’s treatment comparison is therefore only partly supported. (LLM, conf=0.88)

  cites [136] Stroes, 2014, Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab, J Am Coll Cardiol sourceExperimental — accuracy not yet measured

In the paper

“There were similar rates of any adverse event for all treatments; however, fewer events that led to treatment discontinuation and few skeletal muscle-related adverse events occurred with alirocumab (134).”

What the sources say

• Supported

  The Safety and tolerability section reports generally similar overall adverse-event rates across treatment arms and a trend toward fewer discontinuations due to adverse events with alirocumab. Skeletal muscle-related adverse events were significantly less frequent with alirocumab than with atorvastatin; the lower rate versus ezetimibe was a nonsignificant trend. (LLM, conf=0.90)

  cites [134] Moriarty, 2015, Efficacy and safety of alirocumab vs ezetimibe in statin-intolerant patients, with a statin rechallenge arm: the ODYSSEY ALTERNATIVE randomized trial, J Clin Lipidol source

In the paper

“Reductions in LDL cholesterol ranged from 55% and 56% for evolocumab biweekly and monthly plus daily oral placebo, respectively, to 19% and 16% for ezetimibe daily plus biweekly or monthly subcutaneous placebo, respectively.”

What the sources say

• ?Not checked — no full text of the sourcecites [135] Sullivan, 2012, Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: the GAUSS randomized trial, JAMA source
• Partly supported

  Table 2 reports the stated treatment arms and broadly similar LDL-C reductions in GAUSS-2, but the evolocumab figures are reversed: 56.1% for biweekly dosing and 55.3% for monthly dosing. It reports 19.2% and 16.6% for the corresponding ezetimibe arms; 16.6% would round to 17%, not 16%. This paper reports GAUSS-2, not results across GAUSS 1, 2, and 3 and OSLER. (LLM, conf=0.90)

  cites [136] Stroes, 2014, Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab, J Am Coll Cardiol sourceExperimental — accuracy not yet measured

In the paper

“As in those without diabetes, absolute reductions in ASCVD outcomes (CHD death and nonfatal MI) are greatest in people with high baseline ASCVD risk (known ASCVD and/or very high LDL cholesterol levels), but the overall benefits of statin therapy in people with diabetes at moderate or even low risk for ASCVD are convincing (110,111).”

What the sources say

• ?Not checked — no full text of the sourcecites [110] Taylor, 2013, Statins for the primary prevention of cardiovascular disease, Cochrane Database Syst Rev source
• Partly supported

  Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

  cites [111] Carter, 2013, Risk of incident diabetes among patients treated with statins: population based study, BMJ sourceExperimental — accuracy not yet measured

In the paper

“Intensive therapy is indicated because cardiovascular event rates are increased in people with diabetes and established ASCVD, and it has been shown to be of benefit in multiple large meta-analyses and randomized cardiovascular outcomes trials (99,100,108,119,121).”

What the sources say

• Partly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [99] Mihaylova, 2012, The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials, Lancet sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [100] Baigent, 2005, Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins, Lancet source
• ?Not checked — no full text of the sourcecites [108] Kearney, 2008, Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis, Lancet source
• Partly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [119] Cannon, 2015, Ezetimibe added to statin therapy after acute coronary syndromes, N Engl J Med sourceExperimental — accuracy not yet measured
• Partly supported

  Split into 2 atoms — 1 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

  cites [121] Sabatine, 2017, Evolocumab and clinical outcomes in patients with cardiovascular disease, N Engl J Med sourceExperimental — accuracy not yet measured

In the paper

“The trial showed the addition of ezetimibe to a moderate-intensity statin led to a 6.4% relative benefit and a 2% absolute reduction in major adverse cardiovascular events (atherosclerotic cardiovascular events), with the degree of benefit being directly proportional to the change in LDL cholesterol (119).”

What the sources say

• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [119] Cannon, 2015, Ezetimibe added to statin therapy after acute coronary syndromes, N Engl J Med source

In the paper

“Similar LDL cholesterol reductions were demonstrated in the GAUSS 3 trial after 24 weeks (54.5% with evolocumab compared with 16.7% with ezetimibe), with slightly higher rates of musculoskeletal adverse events (20.7% with evolocumab and 28.8% with ezetimibe).”

What the sources say

• Partly supported

  Table 3 reports LDL-C reductions of 54.5% with evolocumab and 16.7% with ezetimibe for the mean of weeks 22 and 24. At week 24 alone, the reductions were 52.8% and 16.7%, respectively. The Safety and Tolerability Outcomes section confirms muscle-related adverse-event rates of 20.7% and 28.8%, with the higher rate in the ezetimibe group. (LLM, conf=0.90)

  cites [137] Nissen, 2016, Efficacy and tolerability of evolocumab vs ezetimibe in patients with muscle-related statin intolerance: the GAUSS-3 randomized clinical trial, JAMA sourceExperimental — accuracy not yet measured

In the paper

“Several studies have reported a modestly increased risk of incident type 2 diabetes with statin use (162,163), which may be limited to those with diabetes risk factors.”

What the sources say

• Supported

  The citation follows the statement about a modest increase in incident diabetes risk, and the Results report a small significant increase across five hypothesis-testing trials (RR 1.13). The Conclusions note that the increase was no longer significant when WOSCOPS was included. The subsequent suggestion about people with diabetes risk factors falls outside the clause directly cited here. (LLM, conf=0.88)

  cites [162] Rajpathak, 2009, Statin therapy and risk of developing type 2 diabetes: a meta-analysis, Diabetes Care source
• ?Not checked — no full text of the sourcecites [163] Sattar, 2010, Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials, Lancet source

In the paper

“Previous randomized controlled trials of aspirin, specifically in people with diabetes, failed to consistently show a significant reduction in overall ASCVD end points, raising questions about the efficacy of aspirin for primary prevention in people with diabetes, although some sex differences were suggested (175-177).”

What the sources say

• Partly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [175] Belch, 2008, The Prevention of Progression of Arterial Disease and Diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease, BMJ sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [176] Zhang, 2010, Aspirin for primary prevention of cardiovascular events in patients with diabetes: a meta-analysis, Diabetes Res Clin Pract source
• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [177] De Berardis, 2009, Aspirin for primary prevention of cardiovascular events in people with diabetes: meta-analysis of randomised controlled trials, BMJ source

In the paper

“Although the evidence is limited, statins did not increase teratogenic effects for individuals with familial hypercholesterolemia (147,148), and a meta-analysis of pravastatin in pregnant individuals showed a reduction in preeclampsia, premature birth, and neonatal intensive care unit admissions (149).”

What the sources say

• ?Not checked — no full text of the sourcecites [147] Botha, 2018, Statins and other lipid-lowering therapy and pregnancy outcomes in homozygous familial hypercholesterolaemia: a retrospective review of 39 pregnancies, Atherosclerosis source
• Partly supported

  Split into 2 atoms — 1 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

  cites [148] Toleikyte, 2011, Pregnancy outcomes in familial hypercholesterolemia: a registry-based study, Circulation sourceExperimental — accuracy not yet measured
• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [149] Mészáros, 2022, Pravastatin in preeclampsia: a meta-analysis and systematic review, Front Med (Lausanne) source

In the paper

“An analysis of one of the initial studies suggested that although statin use was associated with diabetes risk, the cardiovascular event rate reduction with statins far outweighed the risk of incident diabetes, even for individuals at highest risk for diabetes (164).”

What the sources say

• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [164] Ridker, 2012, Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial, Lancet source

In the paper

“Bempedoic acid, a novel LDL cholesterollowering agent acting in the same pathway as statin but without activity in skeletal muscle, which limits the muscle-related adverse effects, lowers LDL cholesterol levels by 15% for those on statins and 24% for those not taking statins (140).”

What the sources say

• Partly supported

  The Results report an approximately 24% LDL-C reduction without background statins, but reductions with statins varied by intensity: 15.67% with high-intensity statins and 19.58% with moderate- or low-intensity statins. The citing sentence omits that qualification when it says 15% for those on statins. The Introduction supports its description of bempedoic acid’s pathway and lack of activation in skeletal muscle. (LLM, conf=0.90)

  cites [140] De Filippo, 2023, Safety and efficacy of bempedoic acid: a systematic review and meta-analysis of randomised controlled trials, Cardiovasc Diabetol sourceExperimental — accuracy not yet measured

In the paper

“In a large trial in people with diabetes, fenofibrate improved cardiovascular outcomes in subgroups with both elevated triglycerides (>200 mg/dL [2.3 mmol/L]) and low HDL cholesterol (<40 mg/dL [1.0 mmol/L]) (156); however, another fibrate, pemafibrate, failed to reduce overall cardiovascular outcomes in a similar population (157).”

What the sources say

• ?Not checked — no full text of the sourcecites [156] Maki, 2016, Triglyceride-lowering therapies reduce cardiovascular disease event risk in subjects with hypertriglyceridemia, J Clin Lipidol source
• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [157] Das Pradhan, 2022, Triglyceride lowering with pemafibrate to reduce cardiovascular risk, N Engl J Med source

In the paper

“Use of low-dose statins was allowed in these studies and was associated with an increase in the incidence of musculoskeletal adverse effects (135,136).”

What the sources say

• ?Not checked — no full text of the sourcecites [135] Sullivan, 2012, Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: the GAUSS randomized trial, JAMA source
• Supported

  The Methods section says GAUSS-2 enrolled patients taking no statin or a low-dose statin. The safety outcomes passage reports more myalgia among low-dose statin users than nonusers in both treatment groups (21% vs. 17% with ezetimibe; 17% vs. 6% with evolocumab). The indexed copy does not provide page numbers for these passages. (LLM, conf=0.92)

  cites [136] Stroes, 2014, Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab, J Am Coll Cardiol source

In the paper

“Individuals of childbearing potential are less likely to be treated with statins or achieve their LDL cholesterol goals based on their cardiovascular risk (144-146).”

What the sources say

• ?Not matched

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

  cites [144] Agarwala, Dyslipidemia management in women of reproductive potential: an expert clinical consensus from the national lipid association, J Clin Lipidol.
• Partly supported

  The 'Call to action' section says high-risk women are less likely than men to receive statins. The 'Familial hypercholesterolaemia' section reports lower LDL-C goal attainment and treatment interruptions around pregnancy in women with FH. These passages do not establish both findings for all individuals of childbearing potential or assess LDL-C goal attainment across cardiovascular-risk levels. (LLM, conf=0.86)

  cites [145] Roeters van Lennep, 2023, Women, lipids, and atherosclerotic cardiovascular disease: a call to action from the European Atherosclerosis Society, Eur Heart J sourceExperimental — accuracy not yet measured
• Partly supported

  The Results (Statin Use and Dosing Intensity; page not provided) show that females eligible for statins were less likely than males to receive a statin or guideline-recommended intensity. The paper does not establish this specifically for individuals of childbearing potential, and its treatment-intensity finding does not show whether patients achieved LDL-cholesterol goals based on cardiovascular risk. (LLM, conf=0.88)

  cites [146] Nanna, 2019, Sex differences in the use of statins in community practice, Circ Cardiovasc Qual Outcomes sourceExperimental — accuracy not yet measured

In the paper

“A trial suggested that more frequent dosing of aspirin may reduce platelet reactivity in individuals with diabetes (195); however, these observations alone”

What the sources say

• Supported

  The Abstract (p. 5) reports that aspirin 100 mg twice daily reduced platelet reactivity more effectively than 100 mg once daily in participants with type 2 diabetes. The citing sentence’s cautious wording is consistent with this trial finding. (LLM, conf=0.94)

  cites [195] Bethel, 2016, Randomized controlled trial comparing impact on platelet reactivity of twice-daily with once-daily aspirin in people with Type 2 diabetes, Diabet Med source

In the paper

“In contrast, major bleeding was significantly increased from 3.2% to 4.1% in the aspirin group (rate ratio 1.29; P = 0.003), with most of the excess being gastrointestinal bleeding and other extracranial bleeding.”

What the sources say

• Supported

  The Results (p. 1) report major bleeding in 4.1% of the aspirin group versus 3.2% of the placebo group (rate ratio 1.29; P = 0.003). The same passage states that most of the excess was gastrointestinal and other extracranial bleeding. (LLM, conf=0.95)

  cites [179] Bowman, 2018, Effects of aspirin for primary prevention in persons with diabetes mellitus, N Engl J Med source

In the paper

“Another meta-analysis raised the hypothesis that low-dose aspirin efficacy is reduced in those weighing >70 kg (196); however, the ASCEND trial found benefit of low-dose aspirin in those in this weight range, which would not validate this suggested hypothesis (179).”

What the sources say

• Supported

  The Results (Low-dose aspirin) report that the reduction in cardiovascular events with 75–100 mg aspirin decreased as weight increased, with a loss of effect at 70 kg or more. The Discussion describes this as ineffectiveness in primary prevention for that weight group and calls for further research to validate the finding. The claim’s “>70 kg” is a slightly different boundary from the paper’s “≥70 kg,” but its hedged summary reflects the finding. (LLM, conf=0.93)

  cites [196] Rothwell, 2018, Effects of aspirin on risks of vascular events and cancer according to bodyweight and dose: analysis of individual patient data from randomised trials, Lancet source

In the paper

“Two other large, randomized trials of aspirin for primary prevention, in people without diabetes (ARRIVE [Aspirin to Reduce Risk of Initial Vascular Events]) (180) and in the elderly (ASPREE [Aspirin in Reducing Events in the Elderly]) (181), in which 11% of participants had diabetes, found no benefit of aspirin on the primary efficacy end point and an increased risk of bleeding.”

What the sources say

• Supported

  The Methods state that ARRIVE excluded people with diabetes. The Discussion reports that aspirin did not lower the risk of major cardiovascular events, and the Results report increased gastrointestinal and other minor bleeding in the aspirin group. The ASPREE details are attributed to a separate citation, not to ARRIVE. (LLM, conf=0.92)

  cites [180] Gaziano, 2018, Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial, Lancet source
• Partly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [181] McNeil, 2018, Effect of aspirin on cardiovascular events and bleeding in the healthy elderly, N Engl J Med sourceExperimental — accuracy not yet measured

In the paper

“The largest reduction was for nonfatal MI, with little effect on CHD death (relative risk 0.95 [95% CI 0.78-1.15])or total stroke.”

What the sources say

• Partly supported

  The Results report that, in primary prevention trials, the reduction in coronary events came mainly from nonfatal MI, with no clear reduction in CHD death; the net effect on stroke was not significant. But the quoted interval for CHD death is a 99% CI, not a 95% CI, and the sentence omits the primary-prevention restriction: the paper reports a significant reduction in total stroke in secondary prevention trials (Findings). (LLM, conf=0.90)

  cites [178] Baigent, 2009, Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials, Lancet sourceExperimental — accuracy not yet measured

In the paper

“In addition, current guidelines recommend short-term dual antiplatelet therapy after high-risk transient ischemic attack and minor stroke (198).”

What the sources say

• Partly supported

  The Recommendation-Specific Supportive Text (page unavailable) says minor strokes meeting POINT trial criteria should receive short-term aspirin and clopidogrel. The 2b B-NR recommendation (page unavailable) says ticagrelor plus aspirin for up to 30 days might be considered after a recent high-risk TIA or minor stroke, but only with concomitant ipsilateral intracranial-artery stenosis. The available passages therefore support short-term dual therapy in specified patients, not an unqualified recommendation for all high-risk TIAs and minor strokes. (LLM, conf=0.78)

  cites [198] Kleindorfer, 2021, 2021 Guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart Association/American Stroke Association, Stroke sourceExperimental — accuracy not yet measured

In the paper

“There were no significant differences by sex, weight, or duration of diabetes or other baseline factors, including ASCVD risk score.”

What the sources say

• Partly supported

  The ‘Effects on Vascular Events and Bleeding According to Baseline Characteristics’ section (p. 6) reports no clear evidence that aspirin’s effects varied by baseline characteristics, including vascular-risk group. The Discussion (p. 9) also says a proposed difference by body weight was not confirmed. Sex and diabetes duration are listed as baseline characteristics (Results, p. 5), but the retrieved text does not report their subgroup results individually; moreover, the paper describes its own predicted five-year vascular-risk score, not an ASCVD risk score. (LLM, conf=0.82)

  cites [179] Bowman, 2018, Effects of aspirin for primary prevention in persons with diabetes mellitus, N Engl J Med sourceExperimental — accuracy not yet measured

In the paper

“Evidence supports use of either ticagrelor or clopidogrel if no percutaneous coronary intervention was performed and clopidogrel, ticagrelor, or prasugrel if a percutaneous coronary intervention was performed (199).”

What the sources say

• Partly supported

  Section 3.2.1–3.2.5 recommends ticagrelor or clopidogrel for patients who have not undergone PCI, and ticagrelor, clopidogrel, or prasugrel for those who have undergone PCI with stent placement. The claim omits the recommendations’ limits to the first year after acute coronary syndrome, the stent-placement condition for the PCI group, and the requirement that each drug be used with low-dose aspirin. (LLM, conf=0.86)

  cites [199] Vandvik, 2012, Primary and secondary prevention of cardiovascular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, Chest sourceExperimental — accuracy not yet measured

In the paper

“however, the ASCEND trial found benefit of low-dose aspirin in those in this weight range, which would not validate this suggested hypothesis (179).”

What the sources say

• Partly supported

  The Discussion (p. 9) says exploratory subgroup analyses did not confirm greater aspirin benefit below 70 kg and observed a trend in the opposite direction. That supports the claim that ASCEND did not validate reduced efficacy above 70 kg, but it does not establish a definitive benefit specifically in the >70 kg subgroup. (LLM, conf=0.85)

  cites [179] Bowman, 2018, Effects of aspirin for primary prevention in persons with diabetes mellitus, N Engl J Med sourceExperimental — accuracy not yet measured

In the paper

“Coronary calcium scoring in asymptomatic people with diabetes may help in risk stratification (214,215) and provide reasoning for treatment intensification and/or guiding informed individual decision-making and willingness for medication initiation and participation.”

What the sources say

• ?Not checked — no full text of the sourcecites [214] Elkeles, 2008, Coronary calcium measurement improves prediction of cardiovascular events in asymptomatic patients with type 2 diabetes: the PREDICT study, Eur Heart J source
• Supported

  The Discussion says CAC scoring further stratifies and reclassifies risk in people with diabetes. The Conclusions propose using measures of subclinical atherosclerosis to personalize preventive treatment intensity, while noting that benefits from CAC-guided treatment have yet to be determined. The claim’s tentative wording reflects that distinction. (LLM, conf=0.88)

  cites [215] Malik, 2017, Coronary artery calcium score for long-term risk classification in individuals with type 2 diabetes and metabolic syndrome from the multi-ethnic study of atherosclerosis, JAMA Cardiol source

In the paper

“The BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) showed that treatment with empagliflozin reduced the composite outcome of MI, stroke, and cardiovascular death by 14% (absolute rate 10.5% vs. 12.1% in the placebo group, HR in the empagliflozin group 0.86 [95% CI 0.74-0.99];P = 0.04 for superiority) and cardiovascular death by 3”

What the sources say

• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [255] Zinman, 2015, Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes, N Engl J Med source

In the paper

“The screening of asymptomatic individuals with high ASCVD risk is not recommended (Fig. 10.5), in part because these high-risk people should already be receiving intensive medical therapy-an approach that provides benefits similar to those of invasive revascularization (208,209).”

What the sources say

• ?Not checked — no full text of the sourcecites [208] Boden, 2007, Optimal medical therapy with or without PCI for stable coronary disease, N Engl J Med source
• Partly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [209] Frye, 2009, A randomized trial of therapies for type 2 diabetes and coronary artery disease, N Engl J Med sourceExperimental — accuracy not yet measured

In the paper

“Risk factors associated with an increased risk for PAD in people with diabetes include age, smoking, hypertension, dyslipidemia, worse glycemic management, longer duration of diabetes, neuropathy, and retinopathy as well as a prior history of cardiovascular disease (237,238).”

What the sources say

• Partly supported

  The Results in the Analytical methods section (page unavailable) identify age, higher HbA1c and systolic blood pressure, lower HDL, current smoking, and prior cardiovascular disease as independent risk factors for incident PVD. The paper also reports increasing PVD prevalence with longer diabetes duration. It does not establish retinopathy or peripheral sensory neuropathy as independent risk factors; they remained in the model because removing them changed the estimate for prior cardiovascular disease. (LLM, conf=0.87)

  cites [237] Adler, 2002, UKPDS 59: hyperglycemia and other potentially modifiable risk factors for peripheral vascular disease in type 2 diabetes, Diabetes Care sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [238] Al-Delaimy, 2004, Effect of type 2 diabetes and its duration on the risk of peripheral arterial disease among men, Am J Med source

In the paper

“This association is not only observed in people with type 2 diabetes but also evident in people with type 1 diabetes (216,217).”

What the sources say

• Supported

  The Results (Time Trends in Incident Heart Failure Hospitalization; page unavailable) state that heart-failure hospitalization rate ratios remained elevated for both types of diabetes compared with no diabetes. The Discussion conclusion likewise says heart failure remains approximately twofold higher in people with diabetes than in those without it, highlighting type 1 diabetes in particular. (LLM, conf=0.93)

  cites [216] McAllister, 2018, Incidence of hospitalization for heart failure and case-fatality among 3.25 million people with and without diabetes mellitus, Circulation source
• Supported

  The Discussion explicitly states that both type 2 and type 1 diabetes are risk factors for heart failure in both sexes. The Results report elevated pooled relative risks for heart failure for each diabetes type in women and men. (LLM, conf=0.95)

  cites [217] Ohkuma, 2019, Diabetes as a risk factor for heart failure in women and men: a systematic review and meta-analysis of 47 cohorts including 12 million individuals, Diabetologia source

In the paper

“SGLT2 inhibitors also reduce risk of heart failure hospitalization and progression of kidney disease in people with established ASCVD, multiple risk factors for ASCVD, or albuminuric kidney disease (268,269).”

What the sources say

• ?Not checked — no full text of the sourcecites [268] Zelniker, 2019, SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials, Lancet source
• Partly supported

  The Results report reduced hospitalization for heart failure and progression of kidney disease in patients with type 2 diabetes, with benefits observed both with and without established ASCVD. They also report no difference in kidney-outcome effectiveness by baseline albuminuria. The claim omits the type 2 diabetes restriction, so this source does not establish the same benefits for all people in the listed groups. (LLM, conf=0.88)

  cites [269] McGuire, 2021, Association of SGLT2 inhibitors with cardiovascular and kidney outcomes in patients with type 2 diabetes: a meta-analysis, JAMA Cardiol sourceExperimental — accuracy not yet measured

In the paper

“After a median follow-up of 3.8 years, LEADER showed that the primary composite outcome (MI, stroke, or cardiovascular death) occurred in fewer participants in the treatment group (13.0%) than in the placebo group (14.9%) (HR 0.87 [95% CI 0.78-0.97];P < 0.001 for noninferiority; P = 0.01 for superiority).”

What the sources say

• Supported

  The Abstract Methods defines the primary composite outcome as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. The Abstract Results reports a median follow-up of 3.8 years and matches both event percentages, the hazard ratio, confidence interval, and P values. (LLM, conf=0.95)

  cites [261] Marso, 2016, Liraglutide and cardiovascular outcomes in type 2 diabetes, N Engl J Med source

In the paper

“in the Effect of Sotagliflozin on Cardiovascular and Renal Events in Participants With Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk (SCORED) trial, randomization to the SGLT1/2 inhibitor sotagliflozin reduced the primary outcome of death from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure in people with type 2 diabetes”

What the sources say

• Supported

  The Methods (p. 2) describe randomization of patients with type 2 diabetes, chronic kidney disease, and cardiovascular risk, and define the stated composite primary end point. The Results (p. 2) report a lower rate of primary end-point events with sotagliflozin than with placebo. The reduction applies to the composite, not necessarily to each component individually. (LLM, conf=0.94)

  cites [284] Bhatt, 2021, Sotagliflozin in patients with diabetes and chronic kidney disease, N Engl J Med source

In the paper

“In Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-Preserved), the primary outcome of cardiovascular death or hospitalization for heart failure was reduced in adults with NYHA functional class I-IV and chronic HFpEF (LVEF >40%), extending the previously seen benefit in people with heart failure to those with preserved ejection fraction”

What the sources say

• Partly supported

  The Discussion reports a lower risk of cardiovascular death or heart-failure hospitalization with empagliflozin in patients with preserved ejection fraction, including those with or without diabetes. The Patients section specifies adults with LVEF >40% but lists NYHA class II–IV as the eligibility criterion, not I–IV. Table 1 records four class I participants; that does not establish the claimed class I–IV study population. (LLM, conf=0.87)

  cites [250] Anker, 2021, Empagliflozin in heart failure with a preserved ejection fraction, N Engl J Med sourceExperimental — accuracy not yet measured

In the paper

“SGLT2 inhibitors reduce the incidence of heart failure and improve heart failurerelated outcomes, including hospitalization for heart failure and heart failure-related symptoms, in people with diabetes with preserved or reduced ejection fraction (250,(255)(256)(257)(298)(299)(300)(301)(302)(303)(304)(305)(306).”

What the sources say

• Supported

  The Introduction reports that SGLT2 inhibitors reduce the development and progression of heart failure in people with type 2 diabetes and describes evidence in reduced-ejection-fraction heart failure. The Discussion reports fewer heart-failure hospitalizations with empagliflozin in preserved-ejection-fraction heart failure, including among patients with diabetes; Table 2 also shows an improvement in the symptom-related KCCQ clinical summary score. The paper’s own trial studied empagliflozin in people with established heart failure, while its broader statements draw on earlier studies. (LLM, conf=0.86)

  cites [250] Anker, 2021, Empagliflozin in heart failure with a preserved ejection fraction, N Engl J Med source
• Partly supported

  The Results (p. 1) and Cardiovascular Outcomes (p. 4) report fewer hospitalizations for heart failure with empagliflozin than with placebo among patients with type 2 diabetes at high cardiovascular risk. The paper does not establish the claimed reduction in heart-failure incidence, improvement in heart-failure symptoms, or benefit specifically in people with preserved or reduced ejection fraction; its finding also concerns empagliflozin rather than the SGLT2 inhibitor class as a whole. (LLM, conf=0.88)

  cites [255] Zinman, 2015, Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes, N Engl J Med sourceExperimental — accuracy not yet measured
• Partly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [256] Neal, 2017, Canagliflozin and cardiovascular and renal events in type 2 diabetes, N Engl J Med sourceExperimental — accuracy not yet measured
• Partly supported

  The Secondary and Exploratory Outcomes section reports fewer hospitalizations for heart failure with canagliflozin than with placebo in patients with type 2 diabetes and kidney disease. It does not establish reduced incidence of heart failure, improved heart-failure symptoms, or benefits specifically in people with preserved or reduced ejection fraction. (LLM, conf=0.88)

  cites [257] Perkovic, 2019, Canagliflozin and renal outcomes in type 2 diabetes and nephropathy, N Engl J Med sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction reports fewer heart-failure hospitalizations with empagliflozin in people with type 2 diabetes and cardiovascular disease, and the Discussion supports a benefit across levels of heart-failure risk. The paper does not report improvement in heart-failure symptoms or establish benefits separately for people with preserved versus reduced ejection fraction; the Discussion says measures of cardiac function were unavailable. Its direct findings concern empagliflozin, not SGLT2 inhibitors as a class. (LLM, conf=0.88)

  cites [298] Fitchett, 2018, Effects of empagliflozin on risk for cardiovascular death and heart failure hospitalization across the spectrum of heart failure risk in the EMPA-REG OUTCOME trial, Eur Heart J sourceExperimental — accuracy not yet measured
• Partly supported

  The Background (p. 2) says SGLT2 inhibitors reduce the risk of a first heart-failure hospitalization in people with type 2 diabetes. The Discussion (p. 8) reports fewer heart-failure hospitalizations and symptoms with dapagliflozin, but this trial enrolled patients with reduced ejection fraction, not preserved ejection fraction; its results therefore do not support that part of the claim. (LLM, conf=0.90)

  cites [299] McMurray, 2019, Dapagliflozin in patients with heart failure and reduced ejection fraction, N Engl J Med sourceExperimental — accuracy not yet measured
• Partly supported

  The Results report fewer hospitalizations for heart failure with SGLT2 inhibitors in patients with type 2 diabetes. The Discussion reports improved heart-failure-related health status in a trial of patients with reduced ejection fraction, but explicitly says benefit in heart failure with preserved ejection fraction remained uncertain. The paper does not establish a reduction in the incidence of heart failure itself. (LLM, conf=0.90)

  cites [300] Arnott, 2020, Sodium-glucose cotransporter 2 inhibition for the prevention of cardiovascular events in patients with type 2 diabetes mellitus: a systematic review and meta-analysis, J Am Heart Assoc sourceExperimental — accuracy not yet measured
• Partly supported

  Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

  cites [301] Nassif, 2021, The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial, Nat Med sourceExperimental — accuracy not yet measured
• Partly supported

  The Results and Efficacy sections report fewer heart-failure hospitalizations and a lower symptom burden with dapagliflozin; the Results say effects were similar in patients with and without diabetes. However, the trial enrolled people who already had heart failure, so it does not establish reduced incidence of new heart failure. It studied ejection fractions above 40%, not the full reduced-ejection-fraction range. Page numbers were not available in our copy. (LLM, conf=0.88)

  cites [302] Solomon, 2022, Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction, N Engl J Med sourceExperimental — accuracy not yet measured
• Partly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [303] Packer, 2020, Cardiovascular and renal outcomes with empagliflozin in heart failure, N Engl J Med sourceExperimental — accuracy not yet measured

In the paper

“A prespecified subgroup analysis from FIGARO-DKD further revealed that in individuals without symptomatic HFrEF, finerenone reduces the risk for new-onset heart failure and improves heart failure outcomes in people with type 2 diabetes and CKD (247).”

What the sources say

• Supported

  The Methods describe these as prespecified FIGARO-DKD analyses in patients with type 2 diabetes and CKD that excluded symptomatic HFrEF (NYHA class II–IV). The Discussion reports a 32% lower risk of new-onset heart failure and significant reductions in heart-failure outcomes with finerenone versus placebo. (LLM, conf=0.94)

  cites [247] Filippatos, 2022, Finerenone reduces risk of incident heart failure in patients with chronic kidney disease and type 2 diabetes: analyses from the FIGARO-DKD trial, Circulation source

In the paper

“Changes to the prespecified primary end points were made prior to unblinding to accommodate a lower-thananticipated number of end point events.”

What the sources say

• Supported

  The End Points section (p. 4) says the original coprimary end points were changed because the trial closed early with fewer events than planned. It also says the investigators and sponsor were unaware of trial-group assignments and had no end-point information from an interim analysis when the change was made. (LLM, conf=0.94)

  cites [284] Bhatt, 2021, Sotagliflozin in patients with diabetes and chronic kidney disease, N Engl J Med source

In the paper

“a large meta-analysis (308) including the EMPEROR-Reduced, EMPEROR-Preserved, DAPA-HF, DELIVER, and the Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post Worsening Heart Failure (SOLOIST-WHF) trials included 21,947 individuals and demonstrated reduced risk for the composite of cardiovascular death or hospitalization for heart failure, cardiovascular death,”

What the sources say

• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [308] Vaduganathan, 2022, SGLT-2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomised controlled trials, Lancet source

In the paper

“Although there were low rates of ketoacidosis in the cardiovascular and heart failure outcomes trials evaluating SGLT inhibition, these studies excluded individuals with type 1 diabetes and/or recent history of diabetic ketoacidosis (309,312).”

What the sources say

• Partly supported

  The Eligibility section (p. 3) required a diagnosis of type 2 diabetes, supporting the statement that this trial did not enroll people with type 1 diabetes. The Safety End Points section (p. 9) mentions diabetic ketoacidosis but refers readers to a supplementary table for its rates; our copy does not establish that rates were low or that a recent history of ketoacidosis was an exclusion criterion. (LLM, conf=0.82)

  cites [309] Bhatt, 2021, Sotagliflozin in patients with diabetes and recent worsening heart failure, N Engl J Med sourceExperimental — accuracy not yet measured
• ?Could not verify

  The Results section reports ketoacidosis risk in SGLT2-inhibitor trials involving people with type 1 diabetes, not rates in cardiovascular or heart-failure outcomes trials. Searches for those trials and for exclusions based on type 1 diabetes or recent ketoacidosis found no passage addressing the claim in our copy. (LLM, conf=0.72)

  cites [312] Musso, 2020, Assessing the risk of ketoacidosis due to sodium-glucose cotransporter (SGLT)-2 inhibitors in patients with type 1 diabetes: a meta-analysis and meta-regression, PLoS Med sourceExperimental — accuracy not yet measured

In the paper

“One of the largest meta-analyses included 73,913 people with diabetes.Compared with a less intensive blood pressure management, allocation to a tighter blood pressure management significantly reduced the risk of stroke by 31% but did not reduce the risk of MI (43).”

What the sources say

• ?Not checked — no full text of the sourcecites [43] Reboldi, 2011, Effects of intensive blood pressure reduction on myocardial infarction and stroke in diabetes: a meta-analysis in 73,913 patients, J Hypertens source

In the paper

“Comorbid conditions including excess body weight and hypertension often precede the development of HFpEF and have been implicated in the pathophysiology of HFpEF (13).”

What the sources say

• ?Not checked — no full text of the sourcecites [13] Redfield, 2023, Heart failure with preserved ejection fraction: a review, JAMA source

In the paper

“Moreover, numerous studies have shown that antihypertensive therapy reduces ASCVD events, heart failure, and microvascular complications.”

In the paper

“The cardiovascular event rates, defined as fatal or nonfatal MI, fatal and nonfatal strokes, and all other cardiovascular events, were not significantly different between diastolic blood pressure goals (#90 mmHg, #85 mmHg, and #80 mmHg), although the lowest incidence of cardiovascular events occurred with an achieved diastolic blood pressure of 82 mmHg.”

What the sources say

• ?Not checked — no full text of the sourcecites [42] Hansson, 1998, Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group, Lancet source

In the paper

“Hypotension occurred more frequently in the intensive treatment group (3.4%) compared with the standard treatment group (2.6%) without significant differences in other adverse events, including dizziness, syncope, or fractures.”

What the sources say

• ?Not checked — no full text of the sourcecites [37] Xie, 2016, Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis, Lancet source

In the paper

“The Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial included nearly 20% of people with diabetes and noted decreased cardiovascular events with treatment of hypertension to a systolic blood pressure goal of <130 mmHg (39).”

What the sources say

• ?Not checked — no full text of the sourcecites [39] Zhang, 2021, Trial of intensive blood-pressure control in older patients with hypertension, N Engl J Med source

In the paper

“More intensive reduction to <130 mmHg was associated with a further reduction in stroke but not other cardiovascular events.”

What the sources say

• ?Not checked — no full text of the sourcecites [35] Bangalore, 2011, 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 source

In the paper

“Current evidence supports managing blood pressure to 110-135/85 mmHg to reduce the risk of accelerated maternal hypertension and to minimize impairment of fetal growth.”

In the paper

“b-Blockers are indicated in the setting of prior MI, active angina, or HFrEF but have not been shown to reduce mortality as blood pressure-lowering agents in the absence of these conditions (33,76,77).”

What the sources say

• ?Not checked — no full text of the sourcecites [33] Ettehad, 2016, Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis, Lancet source
• ?Not checked — no full text of the sourcecites [76] Carlberg, 2004, Atenolol in hypertension: is it a wise choice?, Lancet source
• ?Not checked — no full text of the sourcecites [77] Murphy, 2020, Heart failure with reduced ejection fraction: a review, JAMA source

In the paper

“Another metaanalysis of 19 trials that included 44,989 individuals showed that a mean blood pressure of 133/76 mmHg is associated with a 14% risk reduction for major cardiovascular events compared with a mean blood pressure of 140/81 mmHg (37).This benefit was greatest in people with diabetes.”

What the sources say

• ?Not checked — no full text of the sourcecites [37] Xie, 2016, Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis, Lancet source

In the paper

“Detection and management of these abnormalities is important because AKI and hyperkalemia each increase the risks of cardiovascular events and death (86).”

What the sources say

• ?Not checked — no full text of the sourcecites [86] Hughes-Austin, 2017, The relation of serum potassium concentration with cardiovascular events and mortality in community-living individuals, Clin J Am Soc Nephrol source

In the paper

“The cardiovascular benefit in this large meta-analysis did not depend on baseline LDL cholesterol levels and was linearly related to the LDL cholesterol reduction without a low threshold beyond which there was no benefit observed (108).”

What the sources say

• ?Not checked — no full text of the sourcecites [108] Kearney, 2008, Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis, Lancet source

In the paper

“Statin therapy is a hallmark approach to cardiovascular prevention and treatment; however, a subset of individuals experience partial (inability to tolerate sufficient dosage necessary to achieve therapeutic objectives due to adverse effects) or complete (inability to tolerate any dose) intolerance to statin therapy (133).”

What the sources say

• ?Not checked — no full text of the sourcecites [133] Cheeley, 2022, NLA scientific statement on statin intolerance: a new definition and key considerations for ASCVD risk reduction in the statin intolerant patient, J Clin Lipidol source

In the paper

“The proportions of individuals experiencing adverse events and serious adverse events were similar between the active and placebo treatment groups.”

In the paper

“A meta-analysis of 13 randomized statin trials with 91,140 participants showed an odds ratio of 1.09 for a new diagnosis of diabetes, so that (on average) treatment of 255 individuals with statins for 4 years resulted in one additional case of diabetes while simultaneously preventing 5.4 vascular events among those 255 individuals (163).”

What the sources say

• ?Not checked — no full text of the sourcecites [163] Sattar, 2010, Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials, Lancet source

In the paper

“The risk of rhabdomyolysis is more common with higher doses of statins and renal insufficiency and appears to be higher when statins are combined with gemfibrozil (compared with fenofibrate) (158).”

What the sources say

• ?Not checked — no full text of the sourcecites [158] Jones, 2005, Reporting rate of rhabdomyolysis with fenofibrate + statin versus gemfibrozil + any statin, Am J Cardiol source

In the paper

“and an increased incidence of new-onset diabetes (absolute excess, 1.3 percentage points; P < 0.001) and disturbances in diabetes management among those with diabetes in the HPS2-THRIVE trial in those on combination therapy (161).”

What the sources say

• ?Not checked — no full text of the sourcecites [161] Landray, 2014, Effects of extended-release niacin with laropiprant in high-risk patients, N Engl J Med source

In the paper

“however, these observations alone are insufficient to empirically recommend that higher doses of aspirin be used in this group at this time.”

In the paper

“There is little evidence to support any specific dose, but using the lowest possible dose may help to reduce side effects (190).”

What the sources say

• ?Not checked — no full text of the sourcecites [190] Campbell, 2007, Aspirin dose for the prevention of cardiovascular disease: a systematic review, JAMA source

In the paper

“Thus, aspirin appears to have a modest effect on ischemic vascular events, with the absolute decrease in events depending on the underlying ASCVD risk.”

In the paper

“The net clinical benefit (ischemic benefit vs. bleeding risk) was improved with ticagrelor therapy in the large prespecified subgroup of individuals with history of percutaneous coronary intervention, while no net benefit”

What the sources say

• ?Not checked — no full text of the sourcecites [202] Bhatt, 2019, Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI): a phase 3, placebo-controlled, randomised trial, Lancet source

In the paper

“However, for adults with ASCVD risk >1% per year, the number of ASCVD events prevented will be similar to the number of episodes of bleeding induced, although these complications do not have equal effects on longterm health (182).”

What the sources say

• ?Not checked — no full text of the sourcecites [182] Pignone, 2006, Aspirin, statins, or both drugs for the primary prevention of coronary heart disease events in men: a cost-utility analysis, Ann Intern Med source

In the paper

“Vascular screening was associated with increased pharmacologic therapy (antiplatelet, lipid-lowering, and antihypertensive therapy), reduced inhospital time for PAD and coronary”

What the sources say

• ?Not checked — no full text of the sourcecites [243] Lindholt, 2017, Population screening and intervention for vascular disease in Danish men (VIVA): a randomised controlled trial, Lancet source

In the paper

“However, their routine use leads to radiation exposure and may result in unnecessary invasive testing, such as coronary angiography and revascularization procedures.”

In the paper

“Notably, classical symptoms of claudication are uncommon, and almost half of people with newly diagnosed PAD were asymptomatic (233).”

What the sources say

• ?Not checked — no full text of the sourcecites [233] Hirsch, 2001, Peripheral arterial disease detection, awareness, and treatment in primary care, JAMA source

In the paper

“Treatment with carvedilol reduced mortality by 23%, and there was a 14% risk reduction for heart failure hospitalization.”

What the sources say

• ?Not checked — no full text of the sourcecites [282] Dargie, 2001, Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial, Lancet source

In the paper

“Therefore, management of hypertension constitutes a key goal in people with diabetes and stage A or B heart failure.”

In the paper

“In summary, there are now numerous large randomized controlled trials reporting statistically significant reductions in cardiovascular events for three of the FDA-approved SGLT2 inhibitors (empagliflozin, canagliflozin, and dapagliflozin, with lesser benefits seen with ertugliflozin)”

In the paper

“and four FDA-approved GLP-1 RAs (liraglutide, albiglutide [although that agent was removed from the market for business reasons], semaglutide [lower risk of cardiovascular events in a moderate-sized clinical trial but one not powered as a cardiovascular outcomes trial], and dulaglutide).”

In the paper

“Collectively, these studies indicate that SGLT2 inhibitors reduce the risk for heart failure hospitalization and cardiovascular death in a wide range of people with heart failure.”

In the paper

“The findings on the studied end points were consistent in both trials of heart failure with mildly reduced or preserved ejection fraction and in all five trials combined.”

In the paper

“however, it is not currently approved by the FDA for glycemic management of type 1 or type 2 diabetes.”

In the paper

“This drug is distinct from other SGLT inhibitors, as it lowers glucose via delayed glucose absorption in the gut via inhibition of the cotransporter SGLT1 in addition to increasing urinary glucose excretion;”