Cardiovascular randomized controlled trials (RCTs) typically set composite endpoints as the primary outcome to enhance statistical power. However, influence of individual component endpoints on overall composite outcomes remains understudied.
We searched MEDLINE for RCTs published in 6 high impact journals (the Lancet, the New England Journal of Medicine, Journal of the American Medical Association, Circulation, Journal of the American College of Cardiology and the European Heart Journal) from 2011 to 2017. 2-armed, parallel-design cardiovascular RCTs which reported composite outcomes were included. All-cause or cardiovascular mortality, myocardial infarction (MI), heart failure and stroke were deemed “hard” endpoints, whereas hospitalization, angina, and revascularization were identified as “soft” endpoints. Type of outcome (primary or secondary), event rates in treatment and control groups for the composite outcome and of its components according to predefined criteria.
Of the 45.8% (316/689) cardiovascular RCTs which utilized a composite outcome, 79.4% set the composite as the primary outcome. Death was the most common component (89.8%), followed by MI (66.1%). About 80% of the trials reported complete data for each component. 147 trials (46.5%) incorporated a “soft” endpoint as part of their composite. Death contributed the least to the estimate of effects (R change=0.005) of the composite, while revascularization contributed the most (R change=0.423).
Cardiovascular RCTs frequently employ composite endpoints, which include “soft” endpoints as components in nearly 50% of studies. Higher event rates in composite endpoints may create a misleading interpretation of treatment impact due to large contributions from endpoints with less clinical significance.

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