Cardiology Research, ISSN 1923-2829 print, 1923-2837 online, Open Access |
Article copyright, the authors; Journal compilation copyright, Cardiol Res and Elmer Press Inc |
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Review
Volume 12, Number 4, August 2021, pages 210-218
Update on the Cardiovascular Benefits of Sodium-Glucose Co-Transporter-2 Inhibitors: Mechanism of Action, Available Agents and Comprehensive Review of Literature
Table
Trial name | SGLT2 inhibitor | Primary outcome measure | NNT for the primary outcome | Adverse events |
---|---|---|---|---|
SGLT2: sodium-glucose co-transporter-2; NNT: number needed to treat; MI: myocardial infarction; UTI: urinary tract infection; ESRD: end-stage renal disease; DKA: diabetic ketoacidosis; MACE: major adverse cardiovascular event; HF: heart failure; MRI: magnetic resonance imaging; NT-proBNP: N-terminal pro-B-type natriuretic peptide; KCCQ: Kansas City Cardiomyopathy Questionnaire; LVESV: left ventricular end-systolic volume. | ||||
1. EMPA-REG OUTCOME | Empagliflozin 10 and 25 mg | A composite of cardiovascular death, nonfatal MI (excluding silent MI), or nonfatal strokes | NNT = 63/3.1 years or NNT = 195/1 year | Genital infections, and urosepsis without an increase in the overall rate of UTI, complicated UTI or pyelonephritis) |
2. CANVAS | Canagliflozin 100 and 300 mg | A composite cardiovascular deaths, nonfatal MI, or nonfatal strokes | NNT = 220/1 year | Genital infections, increased rate of amputation, and increased bone fracture (statistically insignificant) |
3. CREDENCE | Canagliflozin 100 mg | A composite of ESRD, serum creatinine baseline doubling, or renal and cardiovascular deaths | NNT = 22/2.5 years | DKA |
4. DECLARE-TIMI 58 | Dapagliflozin 10 mg | MACE for safety; MACE and cardiovascular death or HF hospitalization for efficacy | Not superior for safety, however, NNT = 112/4.2 years or NNT = 470/1 year for efficacy | Genital infections and DKA |
5. VERTIS-CV | Ertugliflozin 5 and 15 mg | MACE | N/A as there was no difference in risk reduction | Genital infections and UTI (statistically significant), with more DKA and amputation events in the ertugliflozin arms |
6. EMPA-HEART | Empagliflozin 10 mg | The delta in left ventricular mass index as noted on cardiac MRI | N/A | N/A |
7. DEFINE-HF | Dapagliflozin 10 mg | Difference in mean NT-proBNP; improvement of ≥ 5 points in the KCCQ or a ≥ 20% decrease in NT-proBNP | N/A | N/A |
8. PRESERVED-HF | Dapagliflozin 10 mg | Symptomatic and physical limitations as measured by the KCCQ | N/A | N/A |
9. DAPA-HF | Dapagliflozin 10 mg | Deaths from cardiovascular causes, HF hospitalization, or urgent HF visit | NNT = 20.4/18 months | No statistically significant difference in adverse events |
10. EMPEROR-REDUCED | Empagliflozin 10 mg | Cardiovascular death or HF hospitalization | NNT = 19/1.3 years | Uncomplicated genital tract infection |
11. EMPEROR-PRESERVED | Empagliflozin 10 mg | Time-to-first-event analysis of the combined risk for cardiovascular death and HF hospitalization | Study is not completed yet | Study is not completed yet |
12. EMBRACE-HF | Empagliflozin 10 mg | The delta change in pulmonary artery pressure from baseline to end of treatment | N/A | N/A |
13. REFORM | Dapagliflozin 10 mg | The difference in LVESV using cardiac MRI | N/A | Decline in renal function, which was transient and resolved after reduction of loop diuretic dose without dapagliflozin dose change |
14. EMPA | Empagliflozin 10 mg | Determining if empagliflozin would improve the loop diuretic’s natriuretic effect | N/A | Not reported |
15. SOLOIST-WHF | Sotagliflozin 400 mg titrated from 200 mg if no side effects | Cardiovascular death, HF hospitalizations, and urgent HF visits | NNT = 7/9 months | Diarrhea, genital fungal infections, and severe hypoglycemia |