Diabetes Metab J > Volume 45(2); 2021 > Article |
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Country/Clinical Trial | Number | Prevalence of diabetes in heart failure patients, % |
---|---|---|
Country | ||
USA, Olmsted County [9] | 25.0 | |
Europe, EuroHeart Failure Survey [10] | 27.0 | |
England, Heart of England Study [11] | 24.0 | |
Italy [12] | 30.0 | |
China, Shanghai [13] | 29.1 | |
Korea, National Sample Cohort [5] | 49.1 | |
Japan, CHART Cohort Study [14] | 47.4 | |
Clinical trial | ||
SOLVD [3] | 2,569 | 25.8 |
MERIT-HF [15] | 3,991 | 24.5 |
CHARM-Alternative [7] | 2,028 | 27.0 |
SHIFT [16] | 6,558 | 30.4 |
EMPHASIS-HF [4] | 2,737 | 31.4 |
PARADIGM-HF [6] | 8,442 | 34.7 |
OPTIME (hospitalized) [17] | 949 | 44.2 |
DAPA-HF [8] | 4,744 | 45.0 |
CHART, Chronic Heart Failure Analysis and Registry in the Tohoku District; SOLVD, Effect of Enalapril on Survival in Patients with Reduced Left Ventricular Ejection Fractions and Congestive Heart Failure; MERIT-HF, Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure; CHARM, Effect of Candesartan for the Management of Patients with Chronic Heart Failure; SHIFT, Systolic Heart Failure Treatment with the If Inhibitor Ivabradine Trial; EMPHASIS-HF, Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms; PARADIGM-HF, Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure; OPTIME, Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure; DAPAHF, Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction.
Variable | ELIXA [63] | LEADER [65] | SUSTAIN-6 [66] | EXSCEL [64] | REWIND [68] | PIONEER-6 [67] |
---|---|---|---|---|---|---|
No. of patients | 6,068 | 9,340 | 3,297 | 14,752 | 9,901 | 3,183 |
Drug | Lixisenatide | Liraglutide | Semaglutide | Exenatide | Dulaglutide | Semaglutide |
Dose | 10 or 20 µg daily | 1.8 mg or max tolerated dose per day | 0.5 or 1 mg sq per week | 2 mg per week | 1.5 mg per week | 14 mg or max tolerated dose per day |
Main inclusion criteria | T2DM+history of ACS (<180 days) | T2DM+CVD, CKD, or HF at ≥50 yr or CV risk at ≥60 yr | T2DM+CVD, CKD, or HF at ≥50 yr or CV risk at ≥60 yr | T2DM±CVD | T2DM+prior ACS or RF for CVD | T2DM+high CVD risk |
Age, yr | 60.3 | 64.3 | 64.6 | 62 | 66.2 | 66.0 |
Female sex, % | 30.7 | 35.7 | 39.3 | 38.0 | 46.3 | 31.6 |
HF patients, % | 22.4 | 17.8 | 23.6 | 16.2 | 8.6 | 12.2 |
Median follow-up, yr | 2.1 | 3.8 | 2.1 | 3.2 | 5.4 | 1.3 |
Primary outcome | 4-point MACEa | 3-point MACEb | 3-point MACEb | 3-point MACEb | 3-point MACEb | 3-point MACEb |
1.02 (0.89-1.17) | 0.87 (0.78-0.97) | 0.74 (0.58-0.95) | 0.91 (0.83-1.00) | 0.88 (0.79-0.99) | 0.79 (0.57-1.11) | |
HF hospitalization | 0.96 (0.75-1.23) | 0.87 (0.73-1.05) | 1.11 (0.77-1.61) | 0.94 (0.78-1.13) | 0.93 (0.77-1.12) | 0.86 (0.48-1.55) |
CV death | 0.98 (0.78-1.22) | 0.78 (0.66-0.93) | 0.90 (0.65-1.48) | 0.88 (0.76-1.02) | 0.91 (0.78-1.06) | 0.49 (0.27-0.92) |
All-cause mortality | 0.94 (0.78-1.13) | 0.85 (0.74-0.97) | 1.05 (0.74-150) | 0.86 (0.77-0.97) | 0.90 (0.80-1.01) | 0.51 (0.31-0.84) |
Values are presented as hazard ratio (95% confidence interval).
ELIXA, Evaluation of Lixisenatide in Acute Coronary Syndrome; LEADER, Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results; SUSTAIN-6, Semaglutide and Cardiovascular outcomes in Patients with Type 2 Diabetes; EXSCEL, Exenatide Study of Cardiovascular Event Lowering; REWIND, Researching Cardiovascular Events with A Weekly Incretin in Diabetes; PIONEER-6, Peptide Innovation for Early Diabetes Treatment; T2DM, type 2 diabetes mellitus; ACS, acute coronary syndrome; CVD, cardiovascular disease; CKD, chronic kidney disease; HF, heart failure; RF, risk factor; CV, cardiovascular; MACE, major adverse cardiovascular event.
Variable | SAVOR-TIMI [75] | EXAMINE [76] | TECOS [77] | CARMELINA [78] | CAROLINA [50] |
---|---|---|---|---|---|
No. of patients | 16,492 | 5,380 | 14,671 | 6,979 | 6,042 |
Drug | Saxagliptin | Alogliptin | Sitagliptin | Linagliptin | Linagliptin |
Dose | 2.5 or 5 mg daily | 12.5 or 25 mg daily | 50 or 100 mg daily | 5 mg | 5 mg |
Main inclusion criteria | T2DM+history of or risk factors for CVD | T2DM+ACS within 15-90 days of randomization | T2DM+history of CVD | T2DM+high CVD and renal risk | T2DM+high CVD risk |
Age, yra | 65.1 | 61.0 | 65.4 | 65.8 | 64.0 |
Female sex, % | 33.1 | 32.1 | 29.9 | 37.1 | 39.9 |
HF patients, % | 12.8 | 27.9 | 18.3 | 26.8 | 4.5 |
Median follow-up, yr | 2.1 | 1.5 | 3.0 | 2.2 | 6.3 |
Primary outcome | 3-point MACEb | 3-point MACEb | 4-point MACEb | 3-point MACEb | 3-point MACEb |
1.00 (0.89-1.12) | 0.96 (95% UL ≤1.16) | 0.98 (0.89-1.08) | 1.02 (0.89-1.17) | 0.98 (0.84-1.14) | |
Heart failure hospitalization | 1.27 (1.07-1.51) | Not reported | 1.00 (0.83-1.20) | 0.90 (0.74-1.08) | 1.21 (0.92-1.59) |
Cardiovascular death | 1.03 (0.87-1.22) | 0.85 (0.66-1.10) | 1.03 (0.89-1.19) | 0.96 (0.81-1.14) | 1.00 (0.81-1.24) |
All-cause mortality | 1.11 (0.96-1.27) | 0.88 (0.71-1.09) | 1.01 (0.90-1.14) | 0.98 (0.84-1.13) | 0.91 (0.78-1.06) |
Values are presented as hazard ratio (95% confidence interval).
SAVOR-TIMI, Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53; EXAMINE, Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care; TECOS, Trial Evaluating Cardiovascular Outcomes with Sitagliptin; CARMELINA, Cardiovascular and Renal Microvascular Outcome Study with Linagliptin in Patients with Type 2 Diabetes Mellitus; CAROLINA, Cardiovascular Outcome Study of Linagliptin versus Glimepiride in Patients with Type 2 Diabetes; T2DM, type 2 diabetes mellitus; CVD, cardiovascular disease; ACS, acute coronary syndrome; HF, heart failure; MACE, major adverse cardiovascular event; UL, upper limit of one-sided confidence interval.
Variable | EMPA-REG OUTCOME [85] | CANVAS Program [86] | DECLARE-TIMI 58 [87] | CREDENCE [88] | DAPA-HF [8] | SOLOIST-WHF [89] | EMPEROR-Reduced [98] | VERTIS-CV [90] | |
---|---|---|---|---|---|---|---|---|---|
No. of patients | 7,020 | 4,330 | 5,812 | 17,160 | 4,401 | 4,744 | 1,222 | 3,730 | 8,246 |
Drug | Empagliflozin | Canagliflozin | Dapagliflozin | Canagliflozin | Dapagliflozin | Sotagliflozin | Empagliflozin | Ertugliflozin | |
Dose | 10 or 25 mg daily | 100 or 300 mg daily | 10 mg daily | 100 mg daily | 10 mg daily | 200 or 400 mg daily | 10 mg daily | 5 or 15 mg daily | |
Main inclusion criteria | T2DM+CVD | T2DM+CVD or >2 CVD risk factors | T2DM+CVD or multiple RF for CVD | T2DM+CKDa | NYHA II- IV+LVEF ≤40% | T2DM+recent HF admission | NYHA II- IV+LVEF ≤40% | CVD+T2DM | |
Age, yr | 63.1 | 63.3 | 64.0 | 63.3 | 66.3 | 69.5 | 66.8 | 64.4 | |
Female sex, % | 28.5 | 35.8 | 37.4 | 35.8 | 23.4 | 33.7 | 23.9 | 23.5 | |
HF patients,% | 10.1 | 14.4 | 10.1 | 14.8 | 100 | 100b | 100 | 23.7 | |
Median follow-up, yr | 3.1 | 5.7 | 2.1 | 4.2 | 2.6 | 1.5 | 0.8 | 1.3 | 3.0 |
Primary outcome | 3-point MACEc | 3-point MACEc | Progression to albuminuriad | 3-point MACEc | 4-point adverse renal outcomese | 3-point CV eventsf | CV death or HF hospitalizations | CV death or HF hospitalizations | 4-point MACE |
0.86 (0.74-0.99) | 0.86 (0.75-0.97) | 0.73 (0.67-0.79) | 0.93 (0.84-1.03) | 0.70 (0.59-0.82) | 0.74 (0.65-0.85) | 0.67 (0.52-0.85) | 0.75 (0.65-0.86) | 0.97 (0.85-1.11) | |
CV death or HF hospitalization | CV death or HF hospitalization | ||||||||
0.83 (0.73-0.95) | 0.88 (0.75-1.03) | ||||||||
Heart failure hospitalization | 0.65 (0.50-0.85) | 0.67 (0.52-0.87) | 0.73 (0.61-0.88) | 0.61 (0.47-0.80) | 0.70 (0.59-0.83) | 0.70 (0.59-0.83) | 0.64 (0.49-0.83) | 0.69 (0.59-0.81) | 0.70 (0.54-0.90) |
CV death | 0.62 (0.49-0.77) | 0.87 (0.72-1.06) | 0.98 (0.82-1.17) | 0.78 (0.61-1.00) | 0.82 (0.69-0.98) | 0.84 (0.58-1.22) | 0.92 (0.75-1.12) | 0.92 (0.77-1.11) | |
All-cause mortality | 0.68 (0.57-0.82) | 0.87 (0.74-1.01) | 0.93 (0.82-1.04) | 0.83 (0.68-1.02) | 0.83 (0.71-0.97) | 0.82 (0.59-1.14) | 0.92 (0.77-1.10) | 0.93 (0.80-1.08) |
Values are presented as hazard ratio (95% confidence interval).
EMPA-REG OUTCOME, Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients; CANVAS, Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes; DECLARE-TIMI 58, Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction; CREDENCE, Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation; DAPA-HF, Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction; SOLOIST-WHF, Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure; EMPEROR-Reduced, Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction; VERTIS-CV, Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes; T2DM, type 2 diabetes mellitus; CVD, cardiovascular disease; RF, risk factor; NYHA, New York Heart Association; LVEF, left ventricular ejection fraction; HF, heart failure; MACE, major adverse cardiovascular event; CV, cardiovascular.
a Chronic kidney disease defined as estimated glomerular filtration rate of 30 to <90 mL/min/1.73 m2 and albuminuria (urinary albumin-to-creatinine ratio, >300 to 5,000 mg/g),
d Progression is defined as the development of micro-albuminuria (urine albumin-to-creatinine ratio [UACR] 30 to 300 mg/g) in participants with normoalbuminuria (UACR <30 mg/g) or macro-albuminuria (UACR >300 mg/g) in patients with micro-albuminuria,
Jia Shen
https://orcid.org/0000-0001-8994-3969
Barry H. Greenberg
https://orcid.org/0000-0002-6605-9385
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