Extrapolating Long-term Event-Free and Overall Survival With Dapagliflozin in Patients With Heart Failure and Reduced Ejection Fraction: An Exploratory Analysis of a Phase 3 Randomized Clinical Trial

Analysis (n=4744) reports that extrapolated event-free (gain of 2.1 years; p = 0.002) and overall (1.7 years; p = 0.03) survival time from a primary composite end point event was longer with dapagliflozin compared with placebo for individuals aged 65 years.

SPS commentary:

The primary composite outcome was time to first hospitalisation for heart failure, urgent heart failure visit requiring intravenous therapy, or cardiovascular death. The trial results were extrapolated to estimate the projected long-term treatment effects of dapagliflozin over the duration of a patient’s lifetime for the primary outcome and the secondary outcome of death from any cause.

According to a commentary, many therapies in CVD, including heart failure are studied in clinical trials that report hazard ratios (HRs) over a follow-up period far shorter than anticipated treatment duration. The HR has known limitations, and alternative measures, such as restricted mean survival time, have been advocated to summarise survival over limited follow-up. It notes however, that in chronic diseases, such as heart failure, treatment effect measures, such as restricted mean survival time, that are limited to clinical trial follow-up may underestimate the gains that could accrue over a lifetime. Thus if patients are expected to continue treatment indefinitely, estimates of lifetime survival benefit can help inform patient, health system, and payer decision-making.

JAMA Cardiology