10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023

In the paper

“Although some variability in calibration exists in various subgroups, including by sex, race, and diabetes, the overall risk prediction does not differ in those with or without diabetes (13 -16), validating the use of risk calculators in people with diabetes.”

What the sources say

• Not checked yetcites [13] Blood Pressure Lowering Treatment Trialists’ Collaboration, 2014, Blood pressure-lowering treatment based on cardiovascular risk: a meta-analysis of individual patient data, Lancet source
• Not checked yetcites [14] Grundy, 2019, 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, J Am Coll Cardiol source
• Not checked yetcites [15] Muntner, 2014, Validation of the atherosclerotic cardiovascular disease Pooled Cohort risk equations, JAMA source
• Not checked yetcites [16] DeFilippis, 2017, Risk score overestimation: the impact of individual cardiovascular risk factors and preventive therapies on the performance of the American Heart Association-American College of Cardiology-Atherosclerotic Cardiovascular Disease risk score in a modern multi-ethnic cohort, Eur Heart J

In the paper

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

In the paper

“Recently, risk scores and other cardiovascular biomarkers have been developed for risk strati fi cation of secondary prevention patients (i.e., those who are already high risk because they have ASCVD) but are not yet in widespread use (17,18).”

What the sources say

• Not checked yetcites [17] Bohula, 2017, Atherothrombotic risk stratification and ezetimibe for secondary prevention, J Am Coll Cardiol source
• Not checked yetcites [18] Bohula, 2016, Atherothrombotic risk stratification and the efficacy and safety of vorapaxar in patients with stable ischemic heart disease and previous myocardial infarction, Circulation source

In the paper

“A recent meta-analysis indicated that SGLT2 inhibitors reduce the risk of heart failure hospitalization, cardiovascular mortality, and all-cause mortality in people with (secondary prevention) and without (primary prevention) cardiovascular disease (12).”

What the sources say

• Not checked yetcites [12] 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 source

In the paper

“Hypertension is often a precursor of heart failure of either type, and ASCVD can coexist with either type (7), whereas prior myocardial infarction (MI) is often a major factor in HFrEF.”

What the sources say

• Not checked yetcites [7] Lam, 2018, Heart failure with preserved ejection fraction: from mechanisms to therapies, Eur Heart J source

In the paper

“these risk calculators do not account for the duration of diabetes or the presence of diabetes complications, such as albuminuria.”

In the paper

“An analysis of trials including people with type 2 diabetes and impaired glucose tolerance with achieved systolic blood pressures of < 135 mmHg in the intensive blood pressure treatment group and < 140 mmHg in the standard treatment group revealed a 10% reduction in all-cause mortality and a 17% reduction in stroke (30).”

What the sources say

• Not checked yetcites [30] 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

“The cardiovascular event rates, de fi ned as fatal or nonfatal MI, fatal and nonfatal strokes, and all other cardiovascular events, were not signi fi cantly different between diastolic blood pressure targets ( # 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 yetcites [37] 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, Lancet source

In the paper

“The results have been interpreted to be generally consistent between both trials, but ACCORD BP was viewed as underpowered due to the composite primary end point being less sensitive to blood pressure regulation (33).”

What the sources say

• Not checked yetcites [33] Wright, 2015, A randomized trial of intensive versus standard blood-pressure control, 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 yetcites [30] 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

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

What the sources say

• Not checked yetcites [34] Zhang, 2021, Trial of intensive blood-pressure control in older patients with hypertension, N Engl J Med source

In the paper

“Moreover, home blood pressure monitoring may improve patient medication taking and thus help reduce cardiovascular risk (25).”

What the sources say

• Not checked yetcites [25] Omboni, 2013, Clinical usefulness and cost effectiveness of home blood pressure telemonitoring: meta-analysis of randomized controlled studies, J Hypertens 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 yetcites [19] 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 yetcites [26] Emdin, 2015, Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis, JAMA source
• Not checked yetcites [27] Arguedas, 2013, Blood pressure targets for hypertension in people with diabetes mellitus, Cochrane Database Syst Rev
• Not checked yetcites [29] Brunström, 2016, Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: systematic review and meta-analyses, BMJ source
• Not checked yetcites [30] 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
• Not checked yetcites [31] Thomopoulos, 2017, Effects of blood-pressure-lowering treatment on outcome incidence in hypertension: 10 - Should blood pressure management differ in hypertensive patients with and without diabetes mellitus? Overview and meta-analyses of randomized trials, J Hypertens source

In the paper

“Randomized clinical trials have demonstrated unequivocally that treatment of hypertension reduces cardiovascular events as well as microvascular complications (26 -32).”

What the sources say

• Not checked yetcites [26] Emdin, 2015, Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis, JAMA source
• Not checked yetcites [27] Arguedas, 2013, Blood pressure targets for hypertension in people with diabetes mellitus, Cochrane Database Syst Rev
• Not checked yetcites [28] Ettehad, 2016, Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis, Lancet source
• Not checked yetcites [29] Brunström, 2016, Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: systematic review and meta-analyses, BMJ source
• Not checked yetcites [30] 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
• Not checked yetcites [31] Thomopoulos, 2017, Effects of blood-pressure-lowering treatment on outcome incidence in hypertension: 10 - Should blood pressure management differ in hypertensive patients with and without diabetes mellitus? Overview and meta-analyses of randomized trials, J Hypertens source
• Not checked yetcites [32] Xie, 2016, Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis, Lancet source

In the paper

“While the ACCORD (Action to Control Cardiovascular Risk in Diabetes) blood pressure trial (ACCORD BP) did not con fi rm that targeting a systolic blood pressure of < 120 mmHg in people with diabetes results in decreased cardiovascular event rates, the prespecifi ed secondary outcome of stroke was reduced by 41% with intensive treatment (35).”

What the sources say

• Not checked yetcites [35] Cushman, 2010, Effects of intensive blood-pressure control in type 2 diabetes mellitus, N Engl J Med source

In the paper

“Of note, the ACCORD BP and SPRINT trials targeted a similar systolic blood pressure < 120 mmHg, but in contrast to SPRINT, the primary composite cardiovascular end point was nonsigni fi cantly reduced in ACCORD BP.”

What the sources say

• Not checked yetcites [33] Wright, 2015, A randomized trial of intensive versus standard blood-pressure control, N Engl J Med source
• Not checked yetcites [35] Cushman, 2010, Effects of intensive blood-pressure control in type 2 diabetes mellitus, N Engl J Med source

In the paper

“This approach acknowledges that the bene fi ts and risks of intensive blood pressure targets are uncertain and may vary across patients and is consistent with a patient-focused approach to care that values patient priorities and health care professional judgment (39).”

What the sources say

• Not checked yetcites [39] de Boer, 2018, Individualizing blood pressure targets for people with diabetes and hypertension: comparing the ADA and the ACC/AHA recommendations, JAMA source

In the paper

“The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that treatment to a target systolic blood pressure of < 120 mmHg decreases cardiovascular event rates by 25% in high-risk patients, although people with diabetes were excluded from this trial (33).”

What the sources say

• Not checked yetcites [33] Wright, 2015, A randomized trial of intensive versus standard blood-pressure control, N Engl J Med source

In the paper

“One of the largest meta-analyses included 73,913 people with diabetes. Compared with a less tight blood pressure control, allocation to a tighter blood pressure control signi fi cantly reduced the risk of stroke by 31% but did not reduce the risk of MI (38).”

What the sources say

• Not checked yetcites [38] 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

“In this trial, 18.9% of patients in the intensive treatment arm and 19.4% in the standard treatment arm had a diagnosis of type 2 diabetes.”

What the sources say

• Not checked yetcites [34] Zhang, 2021, Trial of intensive blood-pressure control in older patients with hypertension, N Engl J Med source

In the paper

“Lifestyle modi fi cation focusing on weight loss (if indicated); application of a Mediterranean or Dietary Approaches to Stop Hypertension (DASH) eating pattern; reduction of saturated fat and trans fat; increase of dietary n-3 fatty acids, viscous fi ber, and plant stanols/sterols intake; and increased physical activity should be recommended to improve the lipid pro fi le and reduce the risk of d”

What the sources say

• Not checked yetcites [83] Mehdi, 2009, Addition of angiotensin receptor blockade or mineralocorticoid antagonism to maximal angiotensin-converting enzyme inhibition in diabetic nephropathy, J Am Soc Nephrol source
• Not checked yetcites [86] Eckel, 2013, 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, Circulation
• Not checked yetcites [87] Arnett, 2019, 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, Circulation

In the paper

“The American College of Obstetricians and Gynecologists also recommends that postpartum individuals with gestational hypertension, preeclampsia, and superimposed preeclampsia have their blood pressures observed for 72 h in the hospital and for 7 -10 days postpartum.”

What the sources say

• Not checked yetcites [51] Irgens, 2001, Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study, BMJ source

In the paper

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

In the paper

“The mean systolic blood pressure achieved in the more intensively treated group was 133.1 ± 0.5 mmHg, and the mean diastolic blood pressure achieved in that group was 85.3 ± 0.3 mmHg.”

What the sources say

• Not checked yetcites [46] Magee, 2015, Less-tight versus tight control of hypertension in pregnancy, N Engl J Med source

In the paper

“Lifestyle management is an important component of hypertension treatment because it lowers blood pressure, enhances the effectiveness of some antihypertensive medications, promotes other aspects of metabolic and vascular health, and generally leads to few adverse effects.”

In the paper

“In CHIPS, targeting 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 targeting a higher diastolic blood pressure.”

What the sources say

• Not checked yetcites [46] Magee, 2015, Less-tight versus tight control of hypertension in pregnancy, N Engl J Med source

In the paper

“Initial treatment for hypertension should include any of the drug classes demonstrated to reduce cardiovascular events in people with diabetes: ACE inhibitors (60,61), ARBs (60,61), thiazide-like diuretics (62), or dihydropyridine calcium channel blockers (63).”

What the sources say

• Not checked yetcites [60] 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 source
• Not checked yetcites [61] Palmer, 2015, Comparative efficacy and safety of blood pressure-lowering agents in adults with diabetes and kidney disease: a network meta-analysis, Lancet source
• Not checked yetcites [62] Barzilay, 2004, Cardiovascular outcomes using doxazosin vs. chlorthalidone for the treatment of hypertension in older adults with and without glucose disorders: a report from the ALLHAT study, J Clin Hypertens (Greenwich) source
• Not checked yetcites [63] Weber, 2010, Cardiovascular events during differing hypertension therapies in patients with diabetes, J Am Coll Cardiol source

In the paper

“Antihypertensive drugs known to be effective and safe in pregnancy include methyldopa, labetalol, and long-acting nifedipine, while hydralzine may be considered in the acute management of hypertension in pregnancy or severe preeclampsia (49).”

What the sources say

• Not checked yetcites [49] American College of Obstetricians and Gynecologists, Task Force on Hypertension in Pregnancy, 2013, Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy, Obstet Gynecol

In the paper

“A similar approach is supported by the International Society for the Study of Hypertension in Pregnancy, which speci fi cally recommends use of antihypertensive therapy to maintain systolic blood pressure between 110 and 140 mmHg and diastolic blood pressure between 80 and 85 mmHg (47).”

What the sources say

• Not checked yetcites [47] Brown, 2018, Hypertensive disorders of pregnancy: ISSHP classification, diagnosis, and management recommendations for international practice, Hypertension source

In the paper

“Treatment with ACE inhibitors or ARBs can cause AKI and hyperkalemia, while diuretics can cause AKI and either hypokalemia or hyperkalemia (depending on mechanism of action) (77,78).”

What the sources say

• Not checked yetcites [77] Nilsson, 2017, Incidence and determinants of hyperkalemia and hypokalemia in a large healthcare system, Int J Cardiol source
• Not checked yetcites [78] Bandak, 2017, Hyperkalemia after initiating renin-angiotensin system blockade: the Stockholm Creatinine Measurements (SCREAM) project, J Am Heart Assoc 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 (79).”

What the sources say

• Not checked yetcites [79] 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

“Intervention reduced risk of primary composite end point of major macrovascular and microvascular events (9%), death from any cause (14%), and death from CVD (18%)”

What the sources say

• Not checked yetcites [36] Patel, 2007, Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial, Lancet source

In the paper

“However, the use of both ACE inhibitors and ARBs in combination, or the combination of an ACE inhibitor or ARB and a direct renin inhibitor, is contraindicated given the lack of added ASCVD bene fi t and increased rate of adverse events -namely, hyperkalemia, syncope, and acute kidney injury (AKI) (71 -73).”

What the sources say

• Not checked yetcites [71] Yusuf, 2008, Telmisartan, ramipril, or both in patients at high risk for vascular events, N Engl J Med source
• Not checked yetcites [72] Fried, 2013, Combined angiotensin inhibition for the treatment of diabetic nephropathy, N Engl J Med source
• Not checked yetcites [73] Makani, 2013, Efficacy and safety of dual blockade of the renin-angiotensin system: meta-analysis of randomised trials, BMJ source

In the paper

“Treatment with ACE inhibitors or ARBs can cause AKI and hyperkalemia, while diuretics can cause AKI and either hypokalemia or hyperkalemia (depending on mechanism of action) (77,78).”

What the sources say

• Not checked yetcites [77] Nilsson, 2017, Incidence and determinants of hyperkalemia and hypokalemia in a large healthcare system, Int J Cardiol source
• Not checked yetcites [78] Bandak, 2017, Hyperkalemia after initiating renin-angiotensin system blockade: the Stockholm Creatinine Measurements (SCREAM) project, J Am Heart Assoc source

In the paper

“Meta-analyses, including data from over 18,000 people with diabetes from 14 randomized trials of statin therapy (mean follow-up 4.3 years), demonstrate a 9% proportional reduction in all-cause mortality and 13% reduction in vascular mortality for each 1 mmol/L (39 mg/dL) reduction in LDL cholesterol (99).”

What the sources say

• Not checked yetcites [99] 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

“These large trials included a signi fi cant number of participants with diabetes and prespeci fi ed analyses on cardiovascular outcomes in people with and without diabetes (109,111,112).”

What the sources say

• Not checked yetcites [109] Giugliano, 2018, Benefit of adding ezetimibe to statin therapy on cardiovascular outcomes and safety in patients with versus without diabetes mellitus: results from IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial), Circulation source
• Not checked yetcites [111] Ray, 2019, 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 source
• Not checked yetcites [112] Sabatine, 2017, 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 source

In the paper

“During the median follow-up of 2.2 years, the composite outcome of cardiovascular death, MI, stroke, hospitalization for angina, or revascularization occurred in 11.3% vs. 9.8% of the placebo and evolocumab groups, respectively, representing a 15% relative risk reduction (P < 0.001).”

What the sources say

• Not checked yetcites [108] Sabatine, 2017, Evolocumab and clinical outcomes in patients with cardiovascular disease, N Engl J Med source

In the paper

“The cardiovascular bene fi t 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 bene fi t observed (99).”

What the sources say

• Not checked yetcites [99] 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

“In contrast, major bleeding was signi fi cantly 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

• Not checked yetcites [144] ASCEND Study Collaborative Group, 2018, Effects of aspirin for primary prevention in persons with diabetes mellitus, N Engl J Med source

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 benefi ts of statin therapy in people with diabetes at moderate or even low risk for ASCVD are convincing (100,101).”

What the sources say

• Not checked yetcites [100] Taylor, 2013, Statins for the primary prevention of cardiovascular disease, Cochrane Database Syst Rev
• Not checked yetcites [101] Carter, 2013, Risk of incident diabetes among patients treated with statins: population based study, BMJ source

In the paper

“Because cardiovascular event rates are increased in people with diabetes and established ASCVD, intensive therapy is indicated and has been shown to be of bene fi t in multiple large meta-analyses and randomized cardiovascular outcomes trials (91,99,105,107,108).”

What the sources say

• Not checked yetcites [91] 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 yetcites [99] Kearney, 2008, Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis, Lancet source
• Not checked yetcites [105] Cannon, 2015, Ezetimibe added to statin therapy after acute coronary syndromes, N Engl J Med source
• Not checked yetcites [107] Cannon, 2004, Intensive versus moderate lipid lowering with statins after acute coronary syndromes, N Engl J Med source
• Not checked yetcites [108] Sabatine, 2017, Evolocumab and clinical outcomes in patients with cardiovascular disease, N Engl J Med source

In the paper

“Accordingly, statins are the drugs of choice for LDL cholesterol lowering and cardioprotection.”

In the paper

“Overall, the addition of ezetimibe led to a 6.4% relative bene fi t and a 2% absolute reduction in major adverse cardiovascular events (atherosclerotic cardiovascular events), with the degree of bene fi t being directly proportional to the change in LDL cholesterol, which was 70 mg/dL in the statin group on average and 54 mg/dL in the combination group (105).”

What the sources say

• Not checked yetcites [105] Cannon, 2015, Ezetimibe added to statin therapy after acute coronary syndromes, N Engl J Med source

In the paper

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

What the sources say

• Not checked yetcites [144] ASCEND Study Collaborative Group, 2018, Effects of aspirin for primary prevention in persons with diabetes mellitus, N Engl J Med source

In the paper

“Evolocumab therapy also signi fi cantly reduced all strokes (1.5% vs. 1.9%; HR 0.79 [95% CI 0.66 -0.95]; P = 0.01) and ischemic stroke (1.2% vs. 1.6%; HR 0.75 [95% CI 0.62 -0.92]; P = 0.005) in the total population, with fi ndings being consistent in individuals with or without a history of ischemic stroke at baseline (115).”

What the sources say

• Not checked yetcites [115] Giugliano, 2020, Stroke prevention with the PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitor evolocumab added to statin in high-risk patients with stable atherosclerosis, Stroke source

In the paper

“The net clinical bene fi t (ischemic bene fi t vs. bleeding risk) was improved with ticagrelor therapy in the large prespecifi ed subgroup of patients with history of percutaneous coronary intervention, while no net benefi t was seen in patients without prior percutaneous coronary intervention (165).”

What the sources say

• Not checked yetcites [165] 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

“A trial suggested that more frequent dosing regimens of aspirin may reduce platelet reactivity in individuals with diabetes (160); however, these observations alone are insuf fi cient to empirically recommend that higher doses of aspirin be used in this group at this time.”

What the sources say

• Not checked yetcites [160] 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

“Another meta-analysis raised the hypothesis that low-dose aspirin ef fi cacy is reduced in those weighing > 70 kg (161); however, the ASCEND trial found bene fi t of low-dose aspirin in those in this weight range, which would thus not validate this suggested hypothesis (144).”

What the sources say

• Not checked yetcites [161] 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

“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 (193).”

What the sources say

• Not checked yetcites [193] Rosenstock, 2019, Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk: the CARMELINA randomized clinical trial, JAMA source

In the paper

“The combined analysis of the two trials found that canagli fl ozin signi fi cantly reduced the composite outcome of cardiovascular death, MI, or stroke versus placebo (occurring in 26.9 vs. 31.5 participants per 1,000 patient-years; HR 0.86 [95% CI 0.75 -0.97]).”

What the sources say

• Not checked yetcites [9] Neal, 2017, Canagliflozin and cardiovascular and renal events in type 2 diabetes, N Engl J Med source

In the paper

“Another meta-analysis raised the hypothesis that low-dose aspirin ef fi cacy is reduced in those weighing > 70 kg (161); however, the ASCEND trial found bene fi t of low-dose aspirin in those in this weight range, which would thus not validate this suggested hypothesis (144).”

What the sources say

• Not checked yetcites [144] ASCEND Study Collaborative Group, 2018, Effects of aspirin for primary prevention in persons with diabetes mellitus, N Engl J Med source

In the paper

“In the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefi ts and Long-term Effectiveness) trial of individuals with established cardiovascular disease, 38% of whom had diabetes, there were no signi fi cant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily (156).”

What the sources say

• Not checked yetcites [156] Jones, 2021, Comparative effectiveness of aspirin dosing in cardiovascular disease, N Engl J Med 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

“Despite abnormal myocardial perfusion imaging in more than one in fi ve patients, cardiac outcomes were essentially equal (and very low) in screened versus unscreened patients.”

What the sources say

• Not checked yetcites [178] Young, 2009, Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial, JAMA source

In the paper

“Previously approved diabetes medications were not subject to the guidance.”

In the paper

“The CANVAS trial that started in 2009 was partially unblinded prior to completion because of the need to fi le interim cardiovascular outcomes data for regulatory approval of the drug (195).”

What the sources say

• Not checked yetcites [195] Neal, 2017, Rationale, design and baseline characteristics of the CANagliflozin cardioVascular Assessment Study-Renal (CANVAS-R): A randomized, placebo-controlled trial, Diabetes Obes Metab source

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 (162).”

What the sources say

• Not checked yetcites [162] 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 source

In the paper

“In prospective studies, coronary artery calcium has been established as an independent predictor of future ASCVD events in people with diabetes and is consistently superior to both the UK Prospective Diabetes Study (UKPDS) risk engine and the Framingham Risk Score in predicting risk in this population (175 -177).”

What the sources say

• Not checked yetcites [175] Elkeles, 2008, Coronary calcium measurement improves prediction of cardiovascular events in asymptomatic patients with type 2 diabetes: the PREDICT study, Eur Heart J source
• Not checked yetcites [176] Raggi, 2004, Prognostic value of coronary artery calcium screening in subjects with and without diabetes, J Am Coll Cardiol source
• Not checked yetcites [177] Anand, 2006, Risk stratification in uncomplicated type 2 diabetes: prospective evaluation of the combined use of coronary artery calcium imaging and selective myocardial perfusion scintigraphy, Eur Heart J source

In the paper

“The effects of dapagli fl ozin therapy were similar in individuals with and without type 2 diabetes.”

What the sources say

• Not checked yetcites [197] Heerspink, 2020, Dapagliflozin in patients with chronic kidney disease, N Engl J Med source

In the paper

“The trial was stopped early due to conclusive evidence of ef fi cacy identi fi ed during a prespeci fi ed interim analysis with no unexpected safety signals.”

What the sources say

• Not checked yetcites [194] Perkovic, 2019, Canagliflozin and renal outcomes in type 2 diabetes and nephropathy, N Engl J Med source

In the paper

“No signi fi cant between-group differences were found for the outcome of all-cause mortality or for a composite renal outcome comprising the fi rst occurrence of long-term dialysis, renal transplantation, or a sustained reduction in eGFR.”

What the sources say

• Not checked yetcites [202] Bhatt, 2021, Sotagliflozin in patients with diabetes and chronic kidney disease, N Engl J Med source

In the paper

“In general, the adverse effects of sotagli fl ozin were similar to those seen with use of SGLT2 inhibitors, but they also included an increased rate of diarrhea potentially related to the inhibition of SGLT1.”

What the sources say

• Not checked yetcites [202] Bhatt, 2021, Sotagliflozin in patients with diabetes and chronic kidney disease, N Engl J Med source

In the paper

“The primary outcome of cardiovascular death, MI, stroke, or hospitalization for unstable angina occurred in 406 patients (13.4%) in the lixisenatide group vs. 399 (13.2%) in the placebo group (HR 1.2 [95% CI 0.89 -1.17]), which demonstrated the noninferiority of lixisenatide to placebo ( P < 0.001) but did not show superiority ( P = 0.81).”

What the sources say

• Not checked yetcites [208] Pfeffer, 2015, Lixisenatide in patients with type 2 diabetes and acute coronary syndrome, N Engl J Med source

In the paper

“An increased risk for diabetic ketoacidosis was noted, however, with 2.2 and 0.2 events per 1,000 patient-years noted in the canagli fl ozin and placebo groups, respectively (HR 10.80 [95% CI 1.39 -83.65]) (194).”

What the sources say

• Not checked yetcites [194] Perkovic, 2019, Canagliflozin and renal outcomes in type 2 diabetes and nephropathy, N Engl J Med source

In the paper

“Ertugli fl ozin was not superior to placebo for the key secondary outcomes of death from cardiovascular causes or hospitalization for heart failure; death from cardiovascular causes; or the composite of death from renal causes, renal replacement therapy, or doubling of the serum creatinine level.”

What the sources say

• Not checked yetcites [201] Cannon, 2020, Cardiovascular outcomes with ertugliflozin in type 2 diabetes, N Engl J Med source

In the paper

“In terms of safety, no signi fi cant increase in lower-limb amputations, fractures, acute kidney injury, or hyperkalemia was noted for canaglifl ozin relative to placebo in CREDENCE.”

What the sources say

• Not checked yetcites [194] Perkovic, 2019, Canagliflozin and renal outcomes in type 2 diabetes and nephropathy, N Engl J Med source

In the paper

“or hospitalization for heart failure (HR 0.71 [95% CI 0.55 -0.92]).”

What the sources say

• Not checked yetcites [197] Heerspink, 2020, Dapagliflozin in patients with chronic kidney disease, N Engl J Med source

In the paper

“SCORED ended early due to a lack of funding; thus, changes to the prespeci fi ed primary end points were made prior to unblinding to accommodate a lower than anticipated number of end point events.”

What the sources say

• Not checked yetcites [202] Bhatt, 2021, Sotagliflozin in patients with diabetes and chronic kidney disease, N Engl J Med source

In the paper

“The incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ signi fi cantly between the two groups.”

What the sources say

• Not checked yetcites [209] Holman, 2017, Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes, N Engl J Med source

In the paper

“The Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial also reported results with the once-weekly GLP-1 receptor agonist extended-release exenatide and found that major adverse cardiovascular events were numerically lower with use of extended-release exenatide compared with placebo, although this difference was not statistically signi fi cant (209).”

What the sources say

• Not checked yetcites [209] Holman, 2017, Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes, N Engl J Med source

In the paper

“Over a median follow-up of 1.8 years, efpeglenatide therapy reduced the risk of incident major adverse cardiovascular events by 27% and of a composite renal outcome event by 32%.”

What the sources say

• Not checked yetcites [214] Gerstein, 2021, Cardiovascular and renal outcomes with efpeglenatide in type 2 diabetes, N Engl J Med source

In the paper

“EMPEROR-Preserved, a randomized double-blinded placebo-controlled trial of 5,988 adults with NYHA functional class I -IV chronic HFpEF (left ventricular ejection fraction > 40%), evaluated the ef fi cacy of empagli fl ozin 10 mg daily versus placebo on top of standard of care on the primary outcome of composite cardiovascular death or hospitalization for heart failure (189).”

What the sources say

• Not checked yetcites [189] Anker, 2021, Empagliflozin in heart failure with a preserved ejection fraction, N Engl J Med source

In the paper

“In 3,730 patients with NYHA class II -IV heart failure with an ejection fraction of # 40%, treatment with empagli fl ozin reduced the combined risk of death, hospitalization for heart failure, or an emergent/urgent heart failure visit requiring intravenous treatment and reduced the total number of hospitalizations for heart failure requiring intensive care, a vasopressor or positive inotropic drug”

What the sources say

• Not checked yetcites [229] Packer, 2021, Effect of empagliflozin on the clinical stability of patients with heart failure and a reduced ejection fraction: the EMPEROR-Reduced trial, Circulation source

In the paper

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

What the sources say

• Not checked yetcites [227] Vaduganathan, 2022, SGLT-2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomised controlled trials, Lancet 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 (212,213).”

What the sources say

• Not checked yetcites [212] 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
• Not checked yetcites [213] McGuire, 2021, Association of SGLT2 inhibitors with cardiovascular and kidney outcomes in patients with type 2 diabetes: a meta-analysis, JAMA Cardiol source

In the paper

“No signi fi cant between-group differences were found in the rates of cardiovascular death or all-cause mortality.”

What the sources say

• Not checked yetcites [228] Bhatt, 2021, Sotagliflozin in patients with diabetes and recent worsening heart failure, N Engl J Med source

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

“In summary, there are now numerous large randomized controlled trials reporting statistically signi fi cant reductions in cardiovascular events for three of the FDA-approved SGLT2 inhibitors (empagli fl ozin, canagli fl ozin, dapagli fl ozin, with lesser bene fi ts seen with ertugli fl ozin)”

What the sources say

• Not checked yetcites [9] Neal, 2017, Canagliflozin and cardiovascular and renal events in type 2 diabetes, N Engl J Med source
• Not checked yetcites [194] Perkovic, 2019, Canagliflozin and renal outcomes in type 2 diabetes and nephropathy, N Engl J Med source
• Not checked yetcites [196] Wiviott, 2019, Dapagliflozin and cardiovascular outcomes in type 2 diabetes, N Engl J Med source

In the paper

“However, the relatively small percentage of such patients enrolled (only 21% of participants had ejection fraction > 50%) and the early termination of the trial limited the ability to determine the effects of sotagli fl ozin in HFpEF speci fi cally.”

What the sources say

• Not checked yetcites [228] Bhatt, 2021, Sotagliflozin in patients with diabetes and recent worsening heart failure, N Engl J Med source

In the paper

“At a median follow-up of 9 months, the rate of primary end point events (the total number of cardiovascular deaths and hospitalizations and urgent visits for heart failure) was lower in the sotaglifl ozin group than in the placebo group (51.0 vs. 76.3; HR 0.67 [95% CI 0.52 -0.85]; P < 0.001).”

What the sources say

• Not checked yetcites [228] Bhatt, 2021, Sotagliflozin in patients with diabetes and recent worsening heart failure, N Engl J Med source

In the paper

“Additional data from the CREDENCE trial with canagli fl ozin showed a 39% reduction in hospitalization for heart failure, and 31% reduction in the composite of cardiovascular death or hospitalization for heart failure, in a diabetic kidney disease population with albuminuria (UACR > 300 to 5,000 mg/g) (194).”

What the sources say

• Not checked yetcites [194] Perkovic, 2019, Canagliflozin and renal outcomes in type 2 diabetes and nephropathy, N Engl J Med source

In the paper

“Similarly, in CANVAS and DECLARE-TIMI 58, there were 33% and 27% reductions in hospitalization for heart failure, respectively, with SGLT2 inhibitor use versus placebo (9,196).”

What the sources say

• Not checked yetcites [9] Neal, 2017, Canagliflozin and cardiovascular and renal events in type 2 diabetes, N Engl J Med source
• Not checked yetcites [196] Wiviott, 2019, Dapagliflozin and cardiovascular outcomes in type 2 diabetes, N Engl J Med source

In the paper

“As discussed in detail in Section 11, ' Chronic Kidney Disease and Risk Management, ' people with diabetes are at an increased risk for CKD, which increases cardiovascular risk (232).”

What the sources say

• Not checked yetcites [232] Gansevoort, 2013, Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention, Lancet source

In the paper

“A prespeci fi ed subgroup analysis from FIGARO-DKD further revealed that in patients without symptomatic HFrEF, fi nerenone reduces the risk for new-onset heart failure and improves heart failure outcomes in people with type 2 diabetes and CKD (187).”

What the sources say

• Not checked yetcites [187] 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