Empagliflozin (EMPA) Reduces Mortality and Hospitalization for Heart Failure (HHF) Irrespective of Cardiovascular (CV) Risk Score at Baseline

In the EMPA-REG OUTCOME trial, EMPA added to standard of care reduced CV death vs. placebo (PBO) by 38% (HR 0.62 [95% CI 0.49, 0.77]), all-cause death by 32% (HR 0.68 [95% CI 0.57, 0.82]) and HHF by 35% (HR 0.65 [95% CI 0.50, 0.85]) in patients with type 2 diabetes and established CV disease. We investigated CV death, all-cause death, HHF and the composite of HHF or CV death by degree of baseline CV risk using the 10-point TIMI Risk Score for Secondary Prevention (TRS 2°P). P-values for treatment-by-subgroup interaction were obtained from tests of homogeneity of treatment group differences among subgroups with no adjustment for multiple testing. Based on the TRS 2°P risk score, of 7020 patients who received study drug in the EMPA-REG OUTCOME trial, 12%, 40%, 30% and 18% were at low, intermediate, high and highest residual CV risk, respectively, at baseline. In the placebo group, from low to highest predicted risk, the proportion of patients with CV death increased from 2.2% to 11.2% and the proportion of patients with HHF increased from 1.1% to 10.0%. Effects of EMPA on CV death, all-cause death, HHF and HHF or CV death were consistent across subgroups by baseline CV risk score (Figure). In conclusion, the benefits of EMPA on key clinical outcomes in the EMPA-REG OUTCOME trial occurred irrespective of the degree of baseline CV risk. Disclosure D.H. Fitchett: Advisory Panel; Self; Boehringer Ingelheim GmbH, Eli Lilly and Company. Speaker9s Bureau; Self; AstraZeneca. Advisory Panel; Self; Amgen Inc., Sanofi. B.M. Scirica: Research Support; Self; AstraZeneca, Eisai Inc., Novartis Pharmaceuticals Corporation, Merck & Co., Inc., Poxel SA. Consultant; Self; AstraZeneca, Biogen, Boehringer Ingelheim Pharmaceuticals, Inc., Covance Inc., Elsevier, GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi, St. Jude Medical, LLC., Dr Reddy9s Laboratory. Other Relationship; Self; Health[at] Scale. S. Inzucchi: Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca, Novo Nordisk Inc., Sanofi, Lexicon Pharmaceuticals, Inc.. Consultant; Self; VTV Therapeutics. Other Relationship; Self; Intarcia Therapeutics, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc., Alere Inc. C.P. Cannon: Research Support; Self; Amgen Inc., Arisaph Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Daiichi Sankyo Company, Limited, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Takeda Pharmaceuticals U.S.A., Inc.. Consultant; Self; Alnylam, Amarin Corporation, Amgen Inc., Arisaph Pharmaceuticals, Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Regeneron Pharmaceuticals, Inc., Sanofi, Eisai Inc., GlaxoSmithKline plc., Kowa Pharmaceuticals America, Inc., Lipimedix, Merck & Co., Inc., Pfizer Inc., Takeda Pharmaceuticals U.S.A., Inc. D.K. McGuire: Consultant; Self; AstraZeneca, Sanofi-Aventis, Eli Lilly and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Pfizer Inc., Novo Nordisk A/S. Research Support; Self; AstraZeneca, Sanofi-Aventis, Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Lexicon Pharmaceuticals, Inc., Eisai Inc., GlaxoSmithKline plc., Esperion Therapeutics. O. Johansen: Employee; Self; Boehringer Ingelheim GmbH. S. Sambevski: Employee; Self; Boehringer Ingelheim GmbH. U. Hehnke: Employee; Self; Boehringer Ingelheim GmbH. J.T. George: Employee; Self; Boehringer Ingelheim GmbH. B. Zinman: Consultant; Self; Novo Nordisk A/S, Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Sanofi, Merck & Co., Inc., Abbott.