Types and Rates of Major Adverse Cardiovascular Events in Antithrombotic Trials: A Systematic Review and...

Area of Science:

• Cardiology
• Neurology
• Clinical Trials

Background:

• Major adverse cardiovascular events (MACE) are key endpoints in antithrombotic therapy trials.
• Definitions and event rates for MACE components can differ between cardiovascular disease and stroke populations.
• Variability exists in MACE and bleeding definitions across studies.

Purpose of the Study:

• To compare MACE component definitions and annualized rates in trials of antithrombotic strategies.
• To analyze bleeding outcomes and participant demographics in secondary prevention trials for stroke and cardiovascular disease, and primary prevention.
• To identify factors influencing event rates in antithrombotic trials.

Main Methods:

• Systematic search of Medline (Ovid) for Phase III randomized controlled trials (2010-2024).
• Inclusion criteria: ≥500 adults, antithrombotic interventions for secondary or primary prevention, reported MACE components, ≥90 days follow-up.
• Meta-regression analysis to explore factors affecting event rates.

Main Results:

• 57 trials (403,957 participants) met inclusion criteria.
• Stroke rates were higher in stroke trials (7.4%/y) vs. cardiovascular trials (1.2%/y).
• Myocardial infarction rates were higher in cardiovascular trials (1.5%/y) vs. stroke trials (0.1%/y).
• Major bleeding and mortality rates were similar across trial types.
• Annualized stroke and mortality rates increased with female participant proportion and decreased with follow-up duration.
• MACE and bleeding definitions were variable.

Conclusions:

• Disease-specific prevention strategies are suggested by differing recurrent event types in stroke vs. cardiovascular trials.
• Standardized MACE and bleeding definitions are recommended to enhance between-trial comparisons and clinical generalizability.