Estimating the Lifetime Benefits of Treatments for Heart Failure

Objectives: This study compared ways of describing treatment effects. The objective was to better explain to clinicians and patients what they might expect from a given treatment, not only in terms of relative and absolute risk reduction, but also in projections of long-term survival. Background: The restricted mean survival time (RMST) can be used to estimate of long-term survival, providing a complementary approach to more conventional metrics (e.g., absolute and relative risk), which may suggest greater benefits of therapy in high-risk patients compared with low-risk patients. Methods: Relative and absolute risk, as well as the RMST, were calculated in heart failure with reduced ejection fraction (HFrEF) trials. Results: As examples, in the RALES trial (more severe HFrEF), the treatment effect metrics for spironolactone versus placebo on heart failure hospitalization and/or cardiovascular death were a hazard ratio (HR) of 0.67 (95% confidence interval [CI]: 0.5 to 0.77), number needed to treat = 9 (7 to 14), and age extension of event-free survival +1.1 years (−0.1 to + 2.3 years). The corresponding metrics for EMPHASIS-HF (eplerenone vs. placebo in less severe HFrEF) were 0.64 (0.54 to 0.75), 14 (1 to 22), and +2.9 (1.2 to 4.5). In patients in PARADIGM-HF aged younger than 65 years, the metrics for sacubitril/valsartan versus enalapril were 0.77 (95% CI: 0.68 to 0.88), 23 (15 to 44), and +1.7 (0.6 to 2.8) years; for those aged 65 years or older, the metrics were 0.83 (95% CI: 0.73 to 0.94), 29 (17 to 83), and +0.9 (0.2 to 1.6) years, which provided evidence of a greater potential life extension in younger patients. Similar observations were found for lower risk patients. Conclusions: RMST event-free (and overall) survival estimates provided a complementary means of evaluating the effect of therapy in relation to age and risk. They also provided a clinically useful metric that should be routinely reported and used to explain the potential long-term benefits of a given treatment, especially to younger and less symptomatic patients.