Statistical Analysis
death, bleeding, PAD, stroke, peripheral artery disease, CHF, CAD, nonadherence, diabetes
CHF, BLEEDING, PERIPHERAL ARTERY DISEASE, CONGESTIVE HEART FAILURE (CHF), CARDIOVASCULAR DISEASE, HYPERLIPIDEMIA, STROKE, PAD, SECONDARY, ATRIAL FIBRILLATION, HYPERTENSION, ASCVD, CORONARY ARTERY DISEASE, CAD, DIABETES
The statistical analysis plan was prespecified before conducting the analyses but after database lock. Baseline characteristics, medical history, and selected concomitant medications are presented separately for participants who took enteric-coated or uncoated aspirin by randomly assigned aspirin dose. Discrete variables are presented as counts and percentages, and continuous variables as medians and IQRs. The χCumulative incidence at median follow-up for primary and secondary effectiveness end points and the primary safety end point was compared between participants taking enteric-coated or uncoated aspirin using unadjusted and multivariable Cox proportional hazards models. Cumulative incidence was calculated at median follow-up (26.2 months; IQR, 19.8-35.4 months) using the Kalbfleisch and Prentice cumulative incidence function estimator and comparisons reported as hazard ratios (HRs) with 95% CI. The Fine-Gray method was used to account for the competing risk of death for nonlethal secondary effectiveness and primary safety outcomes. Primary effectiveness end point, MI, all-cause mortality, and revascularization adjustment measures were randomly assigned treatment, age, current smoking, randomized follow-up strata, no internet use at randomization, race, ethnicity, history of coronary artery disease (CAD), MI, CABG, PCI, ASCVD, hypertension, hyperlipidemia, atrial fibrillation, congestive heart failure (CHF), peripheral artery disease (PAD), prior aspirin use, body mass index (BMI), diabetes, history of bleeding, and baseline P2YTo assess whether the association of aspirin formulation was consistent across randomly assigned aspirin dose for selected end points (primary effectiveness end point, all-cause mortality, and primary safety end point), we included an interaction term in the multivariable Cox proportional hazards models and report tests of the interactions terms. Counts and cumulative incidence at median follow-up with 95% CI are reported by randomized aspirin dose and aspirin formulation. Comparisons of aspirin formulation group, by randomly assigned aspirin dose, are reported as aspirin dose-specific HRs with 95% CI. Cumulative incidence figures reporting the primary effectiveness end point and the primary safety end point are provided by randomly assigned aspirin dose and aspirin formulation. The interaction models were adjusted for covariates prespecified as potential confounders and included age, sex, ethnicity, randomly assigned follow-up stratum (follow-up every 3 or 6 months), race, prior aspirin use, P2YTo account for nonadherence to the randomly assigned aspirin dose, we conducted a sensitivity analysis to assess if aspirin formulation modified the association of time-varying participant-reported aspirin dose with selected study end points (primary effectiveness end point, all-cause death, and primary safety end point). We constructed a Cox proportional hazards model with actual aspirin dose (self-reported at 81 mg, 325 mg, not taking, or other) as a time-varying exposure, an interaction term of time-varying aspirin dose and aspirin formulation reported at baseline, and selected covariates. The HRs were interpreted as the association of current aspirin dose with outcomes. The key assumption for this model was that the decision to switch doses was made for reasons unrelated to the outcome of interest (ie, the primary end point of death, MI, or stroke), beyond the baseline adjustment measures. The adjusted models included age, race, ethnicity, prior aspirin dose, prior MI, prior PCI, history of atrial fibrillation, no internet use at randomization, history of bleeding, and baseline P2YIn an exploratory analysis, we also tested whether there was an interaction with an acid reducing medication (ARM) by formulation of aspirin used. Multivariable Cox proportional hazards models were used to assess whether the association of enteric coating with prespecified end points was modified by the use of ARM. In this analysis, primary end point, nonfatal MI, all-cause mortality, and revascularization adjustment measures were randomly assigned treatment, proton pump inhibitor medication, age, current smoking, randomized follow-up strata (3-month or 6-month intervals), no internet use at randomization, race, ethnicity, history of CAD, MI, CABG, PCI, cardiovascular disease, hypertension, hyperlipidemia, atrial fibrillation, CHF, PAD, prior aspirin use, BMI, and baseline P2YAll hypothesis tests were 2-sided, and 