Risk and risk reduction in trials of heart failure with reduced ejection fraction: absolute or relative?
Harriette G.C. Van Spall, Tauben Averbuch, Kevin Damman, Adriaan A. Voors
Abstract
Randomized clinical trials (RCTs) of heart failure with reduced ejection fraction (HFrEF) typically recruit patients at high risk of clinical outcomes during the follow-up period by including those with severe symptoms, comorbidities, elevated cardiac biomarkers, or a recent hospitalization. 1 By recruiting patients who will likely respond to the intervention and commonly experience outcomes without it, trials can demonstrate treatment efficacy with smaller sample sizes or shorter periods of follow-up. For example, in the CONSENSUS RCT of enalapril in patients with severe symptoms, 253 enrolled patients demonstrated a 40% relative risk reduction (RRR) in 6-month mortality. In contrast, in the SOLVD trial of enalapril in younger patients with less severe symptoms, 2569 patients were enrolled to demonstrate a 16% RRR in 4-year mortality 3 (Table