Mortality Still Matters in Clinical Trials for Heart Failure

Heart failure (HF) remains one of the leading causes of mortality and healthcare costs worldwide. In the ESC HF III Registry, one-year mortality after hospitalization ranged from 16% to 22%, while in the United States it reaches 35.2% among patients ≥ 65 years. Even so, only 1 in 8 post-2015 trials in HF with reduced ejection fraction (HFrEF) demonstrated a reduction in cardiovascular death, in contrast with 13 of 16 pre-2015 trials. This misalignment has driven an increasing reliance on alternative endpoints.

Having participated in the Brazilian coordination of international acute myocardial infarction trials – including ISIS-4, ASSENT-2, and ASSENT-4 PCI^– – all of which used mortality as the central endpoint, it was possible to witness an era in which the primary clinical question was whether a treatment did or did not reduce death. This viewpoint argues that mortality remains the principal endpoint for clinical inference in HF and should not be abandoned in the design of contemporary trials.

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