19-LB: Consistent Cardiovascular (CV) Benefits from Empagliflozin across the Spectrum of CV Risk Factor Control: Post Hoc Analysis from EMPA-REG OUTCOME

Abstract

In the EMPA-REG OUTCOME trial of 7020 patients with T2DM and CV disease, empagliflozin (EMPA) significantly reduced risk for 3P-MACE, CV death, hospitalization for heart failure (HHF) and the composite of HHF or CV death, compared to placebo (PBO). We explored these outcomes in subgroups based on achievement of 7 CV risk factor goals at baseline, defined as: HbA1c <7.5%; LDL-C <100 mg/dL or statin use; systolic BP <140 or diastolic BP <90 mmHg; ACE inhibitor/ARB use; normoalbuminuria; aspirin use; and non-smoking status. Within the PBO group alone, the hazard ratio (HR) for 3P-MACE was 2.21 (95% CI 1.53, 3.19) and 1.42 (1.06, 1.89) for patients achieving 0-3 or 4-5 risk factor goals at baseline, respectively, compared to those reaching 6-7. Similarly, patients achieving only 0-3 or 4-5 goals had increased risk for CV death (HR 4.00 [2.26, 7.11] and 2.48 [1.52, 4.06], respectively), HHF or CV death (HR 2.89 [1.82, 4.57] and 1.90 [1.31, 2.78]) and an increased point estimate for HHF (HR 1.91 [0.96, 3.79] and 1.67 [1.00, 2.80]) versus those achieving 6-7 goals at baseline. EMPA consistently reduced the risk for these CV events versus PBO across all subgroups (p for interaction=NS for all; Figure). In conclusion, CV risk increases with fewer CV risk factors controlled, but the cardioprotective effect of EMPA was consistent regardless of the number of risk factors controlled. Disclosure S.E. Inzucchi: Consultant; Self; vTv Therapeutics, Zafgen, Inc. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi. K. Khunti: Advisory Panel; Self; Amgen Inc., AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis. Speaker’s Bureau; Self; AstraZeneca, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Menarini Group, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Servier, Takeda Pharmaceutical Company Limited. D.H. Fitchett: Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH, Lilly Diabetes. Other Relationship; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S. C. Wanner: Advisory Panel; Self; Bayer AG, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp. Board Member; Self; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Mitsubishi Tanabe Pharma Corporation. M. Mattheus: Employee; Self; Boehringer Ingelheim Pharma GmbH&Co.KG. J. George: Employee; Self; Boehringer Ingelheim International GmbH. A. Ofstad: Employee; Self; Boehringer Ingelheim International GmbH. B. Zinman: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc. Consultant; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc. Funding Boehringer Ingelheim; Eli Lilly and Company