Characterization of cardiovascular clinical events and impact of event adjudication on the treatment effect of darapladib versus placebo in patients with stable coronary heart disease: Insights from the STABILITY trial.

Abstract

BACKGROUND:

Clinical Endpoint Classification (CEC) in clinical trials allows FOR standardized, systematic, blinded, and unbiased adjudication of investigator-reported events. We quantified the agreement rates in the STABILITY trial on 15,828 patients with stable coronary heart disease.

METHODS:

Investigators were instructed to report all potential events. Each reported event was reviewed independently by 2 reviewers according to prespecified processes and prespecified end point definitions. Concordance between reported and adjudicated cardiovascular (CV) events was evaluated, as well as event classification influence on final study results.

RESULTS:

In total, CEC reviewed 7,096 events: 1,064 deaths (696 CV deaths), 958 myocardial infarctions (MI), 433 strokes, 182 transient ischemic attacks, 2,052 coronary revascularizations, 1,407 hospitalizations for unstable angina, and 967 hospitalizations for heart failure. In total, 71.8% events were confirmed by CEC. Concordance was high (>80%) for cause of death and nonfatal MI and lower for hospitalization for unstable angina (25%) and heart failure (50%). For the primary outcome (composite of CV death, MI, and stroke), investigators reported 2,086 events with 82.5% confirmed by CEC. The STABILITY trial treatment effect of darapladib versus placebo on the primary outcome was consistent using investigator-reported events (hazard ratio 0.96 [95% CI 0.87-1.06]) or adjudicated events (hazard ratio 0.94 [95% CI 0.85-1.03]).

CONCLUSIONS:

The primary outcome results of the STABILITY trial were consistent whether using investigator-reported or CEC-adjudicated events. The proportion of investigator-reported events confirmed by CEC varied by type of event. These results should help improve event identification in clinical trials to optimize ascertainment and adjudication.

• Authors: Claes Held, Harvey D White, Ralph A H Stewart, Richard Davies, Shani Sampson, Karen Chiswell, Adam Silverstein, Renato D Lopes, Ulrika Heldestad, Andrzej Budaj, Kenneth W Mahaffey, Lars Wallentin, STABILITY Investigators
• Journal: American heart journal (Am Heart J) Vol. 208 Pg. 65-73 (02 2019) ISSN: 1097-6744 [Electronic] United States
• PMID: 30572273 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Benzaldehydes
• Oximes
• Phospholipase A2 Inhibitors
• Placebos
• darapladib

Topics

• Angina, Unstable (epidemiology)
• Benzaldehydes (therapeutic use)
• Coronary Disease (complications, drug therapy, mortality)
• Endpoint Determination
• Heart Failure (epidemiology)
• Hospitalization (statistics & numerical data)
• Humans
• Ischemic Attack, Transient (epidemiology, etiology)
• Kaplan-Meier Estimate
• Myocardial Infarction (epidemiology, etiology, mortality)
• Oximes (therapeutic use)
• Percutaneous Coronary Intervention (statistics & numerical data)
• Phospholipase A2 Inhibitors (therapeutic use)
• Placebos (therapeutic use)
• Stroke (epidemiology, etiology, mortality)