Abstract Background Naproxen is considered to have a safer cardiovascular profile than ibuprofen, but direct comparisons are scarce and limited to specific patient groups such as patients with osteoarthritis or age50 years. Purpose To compare head-to-head the cardiovascular risks of initiating ibuprofen versus naproxen. Methods This new-user, active-comparator cohort study used nationwide Danish health data (1996–2022) to emulate a target trial comparing the cardiovascular outcomes of ibuprofen versus naproxen initiators. Eligible individuals had no history of non-steroid anti-inflammatory drug prescriptions in the past 365 days, contraindications for non-steroidal anti-inflammatory drugs or conditions associated with low adherence (dementia, alcohol abuse, depression, schizophrenia, benzodiazepine use, or antipsychotic drug use). Outcomes included major vascular events (myocardial infarction, ischemic stroke, or death from ischemic heart disease or stroke) and major coronary events (myocardial infarction and death from ischemic heart disease). Follow-up lasted 30 days or until an event, death, or loss to follow-up. As proxy for intention to treat analyses, we used Cox proportional hazards regression to compute hazard ratios (HRs) with 95% confidence intervals (CIs), adjusting for sex, age, calendar period, co-medications, comorbidities, and socioeconomic position. Results The study included 7,143,555 ibuprofen initiators and 489,110 naproxen initiators. Compared with naproxen initiators, the adjusted HRs comparing ibuprofen vs. naproxen initiators were 1.18 (95% CI: 1.02–1.37) for major vascular events and 1.17 (95% CI: 0.94–1.45) for major coronary events (Please see Figure 1). For individual outcomes, the adjusted HRs were 1.22 (95% CI: 0.96–1.54) for myocardial infarction, 1.28 (95% CI: 1.04–1.49) for ischemic stroke, 1.22 (95% CI: 0.74–2.00) for death from ischemic heart diseases, and 0.96 (95% CI: 0.66–1.39) for death from ischemic heart diseases or stroke. Conclusion Ibuprofen initiators had a higher event rate of major vascular events compared to naproxen initiators. Figure 1. Thirty-day cardiovascular risks in users of ibuprofen versus naproxen, Denmark (1996–2022). Abbreviations: CI, confidence interval. *Consisting of myocardial infarction, ischemic stroke, and vascular death (death from ischemic heart disease or stroke). †Consisting of myocardial infarction and coronary death (death from ischemic heart disease).Figure 1
Bech-Drewes et al. (Sat,) studied this question.