Dapagliflozin quickly lowers risk of heart failure and associated CVA: JAMA

The effects of dapagliflozin ,a SGLT2 inhibitor, on myocardial metabolism, ion transporters, fibrosis, adipokines, and vascular function have also been proposed.These actions, along with preservation of renal function, would also benefit patients with established heart failure. There has been a limited exposure on the efficacy of this drug in such patients.

Researchers undertook the present study to examine timing of onset of clinical benefit with dapagliflozin and magnitude as a function of proximity to prior HF hospitalization.

The study design was a secondary analysis of a completed multinational trial. The Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure trial was a double-blind, placebo-controlled randomized clinical trial of dapagliflozin in patients with chronic HFrEF (n = 4744). From February 2017 to August 2018, the study enrolled patients in New York Heart Association classes II through IV and with left ventricular ejection fraction of 40% or less; the median (range) follow-up time was 18.2 (0-27.8) months. Hazard ratios (HRs) were calculated for the primary efficacy outcome with dapagliflozin vs placebo by time following randomization. Efficacy and safety of dapagliflozin were assessed according to the timing of the most recent HF hospitalization prior to trial enrollment.

Data analysis revealed the following facts.

· A total of 4744 patients were included (1109 women [23.4%]; mean [SD] age, 66.3 [10.9] years).

· The reduction in the primary outcome with dapagliflozin was rapidly apparent, with a sustained statistically significant benefit by 28 days after randomization (HR at 28 days, 0.51 [95% CI, 0.28-0.94]; P = .03).

· A total of 2251 patients (47.4%) had been previously hospitalized for HF, and 1301 (27.4%) had been hospitalized within 12 months prior to enrollment.

· Among patients treated with placebo, there was a stepwise gradient of risk for the primary outcome according to timing of most recent HF hospitalization, with 2-year Kaplan-Meier rates of 21.1%, 25.3%, and 33.8% (adjusted P = .003) for patients with a prior HF hospitalization never, more than 12 months ago, and 12 or fewer months ago, respectively.

· Across these subgroups, dapagliflozin reduced the relative risk of the primary outcome by 16% (HR, 0.84 [95% CI, 0.69-1.01]), 27% (HR, 0.73 [95% CI, 0.54-0.99]), and 36% (HR, 0.64 [95% CI, 0.51-0.80]), respectively (P = .07 for trend).

· Accordingly, patients with a more recent HF hospitalization tended to experience greater absolute risk reductions with dapagliflozin at 2 years: 2.1% (95% CI, -1.9% to 6.1%), 4.1% (95% CI, -3.6% to 11.7%), and 9.9% (95% CI, 3.3%-16.5%), respectively (P = .05 for trend).

For the full article follow the link: 10.1001/jamacardio.2020.7585

Primary source: JAMA Cardiology