Mikhail Kosiborod1, Ingrid Gause-Nilsson2, John Xu3, Christian Sonesson2, Eva Johnsson2. 1. Department of Cardiology, Saint Luke's Mid America Heart Institute and University of Missouri, Kansas City, MO, USA. Electronic address: mkosiborod@saint-lukes.org. 2. AstraZeneca, Gothenburg, Mölndal, Sweden. 3. AstraZeneca, Gaithersburg, MD, USA.
Abstract
AIM: We investigated the efficacy and safety of dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) and heart failure (HF). METHODS: Data for patients randomized to dapagliflozin 10mg or placebo with a history of HF were pooled from five clinical trials. HbA1c, weight and systolic blood pressure (SBP; two studies) were examined up to 52weeks using longitudinal repeated-measures models. Composite cardiovascular outcomes, hospitalizations for HF (HHF), and adverse events (AEs) were also assessed. RESULTS:Patients (mean age 64years, T2DM duration ~14years, HbA1c 8.2%, ~50% with New York Heart Association Class ≥II) received dapagliflozin (N=171) or placebo (N=149). Dapagliflozin produced clinically meaningful placebo-adjusted reductions in HbA1c (-0.55%; 95% confidence interval [CI]: -0.80, -0.30), weight (-2.67kg; 95% CI: -3.88, -1.47), and SBP (-2.05mmHg; 95% CI: -5.68, 1.57) over 52weeks. HHF was rare, but numerically lower with dapagliflozin (n=1 [0.6%]) vs placebo (n=7 [4.7%]). Point estimates for hazard ratios of composite cardiovascular outcomes favored dapagliflozin vs placebo, although 95% CIs crossed unity. CONCLUSIONS:Dapagliflozin produced clinically meaningful reductions in HbA1c, weight, and SBP in patients with T2DM and HF, and was well tolerated.
RCT Entities:
AIM: We investigated the efficacy and safety of dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) and heart failure (HF). METHODS: Data for patients randomized to dapagliflozin 10mg or placebo with a history of HF were pooled from five clinical trials. HbA1c, weight and systolic blood pressure (SBP; two studies) were examined up to 52weeks using longitudinal repeated-measures models. Composite cardiovascular outcomes, hospitalizations for HF (HHF), and adverse events (AEs) were also assessed. RESULTS:Patients (mean age 64years, T2DM duration ~14years, HbA1c 8.2%, ~50% with New York Heart Association Class ≥II) received dapagliflozin (N=171) or placebo (N=149). Dapagliflozin produced clinically meaningful placebo-adjusted reductions in HbA1c (-0.55%; 95% confidence interval [CI]: -0.80, -0.30), weight (-2.67kg; 95% CI: -3.88, -1.47), and SBP (-2.05mmHg; 95% CI: -5.68, 1.57) over 52weeks. HHF was rare, but numerically lower with dapagliflozin (n=1 [0.6%]) vs placebo (n=7 [4.7%]). Point estimates for hazard ratios of composite cardiovascular outcomes favored dapagliflozin vs placebo, although 95% CIs crossed unity. CONCLUSIONS:Dapagliflozin produced clinically meaningful reductions in HbA1c, weight, and SBP in patients with T2DM and HF, and was well tolerated.
Authors: Mark C Petrie; Subodh Verma; Kieran F Docherty; Silvio E Inzucchi; Inder Anand; Jan Belohlávek; Michael Böhm; Chern-En Chiang; Vijay K Chopra; Rudolf A de Boer; Akshay S Desai; Mirta Diez; Jaroslaw Drozdz; Andre Dukát; Junbo Ge; Jonathan Howlett; Tzvetana Katova; Masafumi Kitakaze; Charlotta E A Ljungman; Béla Merkely; Jose C Nicolau; Eileen O'Meara; Pham Nguyen Vinh; Morten Schou; Sergey Tereshchenko; Lars Køber; Mikhail N Kosiborod; Anna Maria Langkilde; Felipe A Martinez; Piotr Ponikowski; Marc S Sabatine; Mikaela Sjöstrand; Scott D Solomon; Per Johanson; Peter J Greasley; David Boulton; Olof Bengtsson; Pardeep S Jhund; John J V McMurray Journal: JAMA Date: 2020-04-14 Impact factor: 56.272
Authors: John J V McMurray; David L DeMets; Silvio E Inzucchi; Lars Køber; Mikhail N Kosiborod; Anna M Langkilde; Felipe A Martinez; Olof Bengtsson; Piotr Ponikowski; Marc S Sabatine; Mikaela Sjöstrand; Scott D Solomon Journal: Eur J Heart Fail Date: 2019-03-21 Impact factor: 15.534