Generalisability of trials on antithrombotic treatment intensification in patients with cardiovascular disease

Abstract

OBJECTIVE: Assessment of generalisability of guideline-informing trials on antithrombotic treatment intensification to real-world patients with cardiovascular disease (CVD). METHODS: Inclusion and exclusion criteria of the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS), Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA), Prevention of Cardiovascular events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction (PEGASUS-TIMI) and Dual Antiplatelet Therapy (DAPT) study were applied to coronary artery disease (CAD) and/or peripheral artery disease (PAD) patients from Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) to determine real-world eligibility. Eligible and ineligible patients were compared on baseline characteristics, cardiovascular events, major bleeding and mortality. RESULTS: Eligibility ranged from 11%-94% for CAD to 75%-90% for patients with PAD. Cardiovascular, bleeding and mortality risks were higher in COMPASS-eligible patients with CAD (rate ratios (RR) 1.98 (95% CI 1.74 to 2.26), 2.02 (95% CI 1.47 to 2.78) and 3.11 (95% CI 2.71 to 3.57), respectively) and CHARISMA-eligible patients (RR 1.51 (95% CI 1.12 to 2.06), 2.25 (95% CI 1.01 to 6.21) and 4.43 (95% CI 2.79 to 7.51), respectively), and lower in COMPASS-eligible patients with PAD (RR 0.45 (95% CI 0.36 to 0.56), 0.29 (95% CI 0.18 to 0.46) and 0.45 (95% CI 0.38 to 0.54), respectively) and DAPT-eligible patients with CAD (RR CVD 0.49 (95% CI 0.34 to 0.69) and mortality 0.67 (95% CI 0.48 to 0.94)) than ineligible patients. After adjustment for trial eligibility criteria, only higher cardiovascular and mortality risks in COMPASS-eligible patients with CAD and lower cardiovascular risks in CHARISMA-eligible and DAPT-eligible patients persisted with CAD. CONCLUSION: A large proportion of contemporary CVD patients would be eligible for intensified antithrombotic treatment trials, with mostly similar adjusted event risks to ineligible patients. Trial-based guideline recommendations are largely applicable to real-world patients.