Prior studies have suggested that non-steroidal anti-inflammatory drugs (NSAIDs) may be associated with higher cardiovascular risks. Few were active-comparison studies that directly assessed potential differential cardiovascular risk between NSAID classes or across individual NSAIDs. We compared the risk of major cardiovascular events between cyclooxygenase-2 enzyme (COX-2) selective NSAIDs and nonselective NSAIDs in patients with hypertension.
We conducted a cohort study of patients with hypertension who initiated COX-2 selective NSAIDs or nonselective NSAIDs in a population-based Taiwanese database. The outcomes were major cardiovascular events of hospitalization for ischemic stroke, acute myocardial infarction, congestive heart failure, transient ischemic attack, unstable angina, or coronary revascularization. We followed patients for up to 4 weeks based on the as-treated principle. We used inverse probability weighting to control for baseline and time-varying covariates to estimate the on-treatment hazard ratios (HRs) and 95% conservative confidence interval (CIs).
We identified 2,749 eligible COX-2 selective NSAID users and 52,880 eligible nonselective NSAID users. The HR of major cardiovascular events comparing COX-2 selective NSAIDs to nonselective NSAIDs after adjusting for baseline and time-varying covariates was 1.07 (95% CI, 0.65-1.74). We did not observe a differential risk when comparing celecoxib to diclofenac (HR, 1.17; 95% CI, 0.61-2.25), ibuprofen (HR, 1.36; 95% CI, 0.58-3.18), or naproxen (HR, 0.75; 95% CI, 0.23-2.44). There was an increased risk with COX-2 selective NSAIDs, however, when comparing COX-2 to mefenamic acid (HR, 2.11; 95% CI, 1.09-4.09).
Our results provide important information about the comparative cardiovascular safety of NSAIDs in patients with hypertension.