Yousif Ahmad1, Mahesh V Madhavan2,3, Gregg W Stone3,4, Darrel P Francis5, Raj Makkar6, Deepak L Bhatt7, James P Howard5. 1. Yale School of Medicine, Yale University, Suite 101, 135 College Street, New Haven, CT 06510, USA. 2. Columbia University Irving Medical Center, NewYork-Presbyterian Hospital, New York, NY 10032, USA. 3. The Cardiovascular Research Foundation, New York, NY 10019, USA. 4. The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. 5. National Heart and Lung Institute, Imperial College London, London, W2 0HS, UK. 6. Smidt Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA. 7. Heart & Vascular Center, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Suite 7022, Boston, MA 02115, USA.
Abstract
AIMS: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have now been evaluated for the treatment of heart failure in several placebo-controlled randomized controlled trials (RCTs) across various ejection fraction ranges, but these trials were powered for composite outcomes rather than individual clinical endpoints. We therefore performed a meta-analysis to assess their safety and efficacy on all-cause mortality, cardiovascular mortality, and heart failure hospitalizations. METHODS AND RESULTS: We performed a prospectively registered random-effects meta-analysis of all RCTs comparing SGLT-2 inhibitors to placebo in patients with heart failure. The pre-specified primary endpoint was all-cause mortality. Secondary endpoints included cardiovascular mortality, heart failure hospitalizations, and the composite of cardiovascular mortality or heart failure hospitalization. Four trials with 15 684 patients were eligible. The SGLT-2 inhibitor tested was empagliflozin in two trials, dapagliflozin in one trial, and sotagliflozin in one trial. The weighted-mean follow-up was 20.0 months. The hazard ratio (HR) for all-cause mortality was 0.91, 95% confidence interval (CI) 0.82-1.01, P = 0.071. There was a 12% reduction in cardiovascular mortality (HR 0.88, 95% CI 0.79 to 0.97, P = 0.012), and a 30% reduction in heart failure hospitalization (HR 0.70, 95% CI 0.64 to 0.77, P < 0.001). CONCLUSION: SGLT-2 inhibitors significantly reduced cardiovascular mortality and heart failure hospitalizations in patients with heart failure. The effect appears consistent across three drugs studied in four trials. SGLT-2 inhibitors should become standard care for patients with heart failure.
AIMS: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have now been evaluated for the treatment of heart failure in several placebo-controlled randomized controlled trials (RCTs) across various ejection fraction ranges, but these trials were powered for composite outcomes rather than individual clinical endpoints. We therefore performed a meta-analysis to assess their safety and efficacy on all-cause mortality, cardiovascular mortality, and heart failure hospitalizations. METHODS AND RESULTS: We performed a prospectively registered random-effects meta-analysis of all RCTs comparing SGLT-2 inhibitors to placebo in patients with heart failure. The pre-specified primary endpoint was all-cause mortality. Secondary endpoints included cardiovascular mortality, heart failure hospitalizations, and the composite of cardiovascular mortality or heart failure hospitalization. Four trials with 15 684 patients were eligible. The SGLT-2 inhibitor tested was empagliflozin in two trials, dapagliflozin in one trial, and sotagliflozin in one trial. The weighted-mean follow-up was 20.0 months. The hazard ratio (HR) for all-cause mortality was 0.91, 95% confidence interval (CI) 0.82-1.01, P = 0.071. There was a 12% reduction in cardiovascular mortality (HR 0.88, 95% CI 0.79 to 0.97, P = 0.012), and a 30% reduction in heart failure hospitalization (HR 0.70, 95% CI 0.64 to 0.77, P < 0.001). CONCLUSION: SGLT-2 inhibitors significantly reduced cardiovascular mortality and heart failure hospitalizations in patients with heart failure. The effect appears consistent across three drugs studied in four trials. SGLT-2 inhibitors should become standard care for patients with heart failure.
Authors: Deepak L Bhatt; Michael Szarek; Bertram Pitt; Christopher P Cannon; Lawrence A Leiter; Darren K McGuire; Julia B Lewis; Matthew C Riddle; Silvio E Inzucchi; Mikhail N Kosiborod; David Z I Cherney; Jamie P Dwyer; Benjamin M Scirica; Clifford J Bailey; Rafael Díaz; Kausik K Ray; Jacob A Udell; Renato D Lopes; Pablo Lapuerta; P Gabriel Steg Journal: N Engl J Med Date: 2020-11-16 Impact factor: 91.245
Authors: Faiez Zannad; João Pedro Ferreira; Stuart J Pocock; Stefan D Anker; Javed Butler; Gerasimos Filippatos; Martina Brueckmann; Anne Pernille Ofstad; Egon Pfarr; Waheed Jamal; Milton Packer Journal: Lancet Date: 2020-08-30 Impact factor: 79.321
Authors: Karin Rådholm; Gemma Figtree; Vlado Perkovic; Scott D Solomon; Kenneth W Mahaffey; Dick de Zeeuw; Greg Fulcher; Terrance D Barrett; Wayne Shaw; Mehul Desai; David R Matthews; Bruce Neal Journal: Circulation Date: 2018-07-31 Impact factor: 29.690
Authors: Antonius Baartscheer; Cees A Schumacher; Rob C I Wüst; Jan W T Fiolet; Ger J M Stienen; Ruben Coronel; Coert J Zuurbier Journal: Diabetologia Date: 2016-10-17 Impact factor: 10.122
Authors: Jan-Per Wenzel; Julius Nikorowitsch; Ramona Bei der Kellen; Christina Magnussen; Renate Bonin-Schnabel; Dirk Westermann; Raphael Twerenbold; Paulus Kirchhof; Stefan Blankenberg; Benedikt Schrage Journal: ESC Heart Fail Date: 2022-04-20