Assessment of Clinical Worsening End Points as a Surrogate for Mortality in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Clinical worsening (CW) is a composite end point commonly used in pulmonary arterial hypertension (PAH) trials. We aimed to assess the trial-level surrogacy of CW for mortality in PAH trials, and whether the various CW components were similar in terms of frequency of occurrence, treatment-related relative risk (RR) reduction, and importance to patients.

Methods: We searched MEDLINE, Embase, and the Cochrane Library (January 1990 to December 2020) for trials evaluating the effects of PAH therapies on CW.