Estimating the Lifetime Benefits of Treatments for Heart Failure

Figures

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  Figure 1. RMST Using Age Instead of Time for the Trials Included The restricted mean survival time (RMST) is expressed in potential years gained without an event from 60 to 80 years of age. The number of patients at risk represents the number of patients who were enrolled in the trial(s) in whom the event of interest had not occurred at a given age. A longer potential life extension (area under the Kaplan-Meier curve) was observed for patients at lower risk. Because they were less likely to have events or dying during follow-up, their potential life extension was improved with treatment. (A) PARADIGM-HF (Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure): potential years gained without event were observed across all the age groups in patients treated with sacubitril/valsartan (vs. enalapril), especially for the composite outcome of cardiovascular death (CVD) or heart failure hospitalization (HFH). (B) RALES (The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure): high-risk population, the potential years gained without event in favor of spironolactone (vs. placebo) were observed especially at younger ages within the trial. (C)…

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  Figure 2. PARADIGM-HF: RMST Using Age Instead of Time in Subgroups Reflecting Patient Risk and Age The number of patients at risk represents the number of patients who were enrolled in the trial(s) in whom the event of interest had not occurred at a given age. A longer potential life extension (area under the Kaplan-Meier curve) was observed for patients with lower N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels, who were in New York Heart Association (NYHA) functional class I and/or II, and were younger than 65 years, which suggested that the long-term benefits of sacubitril/valsartan were particularly important in less symptomatic and younger patients (i.e., patients with lower risk). Abbreviations as in Figure 1.

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  Central Illustration. Comparison of Age-Based Lifetime Estimates Using the Restricted Mean Survival Time With Conventional Measures of Risk Reduction The restricted mean survival time (RMST) using age instead of time allows the estimation of long-term, event-free survival, which is a clinically meaningful metric for both the clinicians and patients. The projections of long-term survival may be particularly useful for explaining the potential long-term benefits of treatments to less symptomatic/lower risk patients. In contrast, the absolute risk reduction may be less pronounced in lower risk patients, which may discourage them from taking additional therapies that could substantially increase the long-term event-free time. DIG = The Effect of Digoxin on Mortality and Morbidity in Patients with Heart Failure; EMPHASIS-HF = Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms; Eple. = eplerenone; HF = heart failure; HR = hazard ratio; PARADIGM-HF = Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure; RALES = The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure Sac./Val. = sacubitril/valsartan; Spiro. = spironolactone.