Dapagliflozin most effective in frail patients with heart failure

Treatment with dapagliflozin results in improvements in all outcomes, regardless of frailty status, among patients with symptomatic heart failure (HF) with reduced ejection fraction, reports a study. However, “more frail” patients have larger absolute reductions.

A post hoc analysis of a phase III randomized clinical trial was conducted in 410 sites in 20 countries involving patients with symptomatic HF with a left ventricular ejection fraction of ≤40 percent and elevated natriuretic peptide.

A total of 4,744 patients were randomized to the addition of once-daily dapagliflozin 10 mg or placebo to guideline-recommended therapy. Worsening HF or cardiovascular death was the primary outcome.

Some 4,742 patients had a calculable frailty index (FI). Of these, 2,392 (50.4 percent) were in FI class 1 (FI ≤0.210; not frail), 1,606 (33.9 percent) in FI class 2 (FI 0.211 to 0.310; “more frail”), and 744 (15.7 percent) in FI class 3 (FI ≥0.311; “most frail”).

Over a median follow-up of 18.2 months, dapagliflozin reduced the risk for the primary outcome, regardless of FI class. The differences in event rate per 100 person-years for dapagliflozin vs placebo were ‒3.5 (95 percent confidence interval [CI], ‒5.7 to ‒1.2) for FI class 1, ‒3.6 (95 percent CI, ‒6.6 to ‒0.5) for FI class 2, and ‒7.9 (95 percent C(, ‒13.9 to ‒1.9) for FI class 3.

While benefits were consistent for other clinical events and health status, the “most frail” patients enjoyed generally larger absolute reductions.

Of note, treatment discontinuation and serious adverse events were comparable between dapagliflozin and placebo, regardless of FI class.

The study was limited by the enrolment criteria, which did not include very high-risk patients.