Replication of the ISAR-REACT 5 Antiplatelet Trial in Healthcare Claims Data

This is a non-randomized, non-interventional study that is part of the RCT DUPLICATE initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to replicate, as closely as possible in healthcare insurance claims data, the trial listed below/above. Although many features of the trial cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial. Randomization is also not replicable in healthcare claims data but was proxied through a statistical balancing of measured covariates through standard practice. Investigators assume that the RCT provides the reference standard treatment effect estimate and that failure to replicate RCT findings is indicative of the inadequacy of the healthcare claims data for replication for a range of possible reasons and does not provide information on the validity of the original RCT finding.

Criteria:

Please see https://drive.google.com/drive/folders/1WD618wrywYjEaXzfLTcuK-VCcnb6b-gV for full code and algorithm definitions.

Inclusion criteria

• Hospitalization for unstable angina or acute MI AND age >= 18 years Days [ACS admission]
• STEMI OR NSTEMI/unstable angina (during admission) + 1 of the following

• >= 60 years old Days [ACS]
• >= 3 risk factors for coronary artery disease
• Diabetes mellitus
• Chronic renal disease
• Carotid stenosis >= 50% or cerebral revascularization
• Peripheral artery disease Days [-365, ACS]
• Aspirin use
• Angina Days [-7, ACS]
• Prior MI or CABG any time prior

Exclusion criteria

• Acute complication PCI Days [-30, ACS admission]
• History of any stroke or TIA Days [all available data, 0]
• Intracranial neoplasm, intracranial AVM, intracranial neoplasm Days [-180, 0]
• Active bleeding Days [-180, 0]
• Platelet count < 100.000/uL Days [-180, 0]
• Anemia (hemoglobin < 10 g/dL) Days [-180, 0]
• Chronic renal insufficiency requiring dialysis Days [-180, 0]
• Moderate to severe hepatic dysfunction Days [-180, 0]
• Increased risk of bradycardia events Days [-180, 0]
• Life expectancy, 1 year Days [-180, 0]
• Pregnancy Days [-180, 0]
• Concomitant therapy CYP3A inhibitors, CYP3A substrates, or strong CYP3A inducers Days [-14, 0]