Ibuprofen for Acute Pericarditis and Associated Cardiovascular Risks: A Danish Nationwide Population-Based Cohort Study

Purpose: Ibuprofen is used to treat acute pericarditis, but high-dose ibuprofen has also been associated with increased cardiovascular risks. We examined the cardiovascular safety of using ibuprofen for acute pericarditis. Patients and Methods: A Danish nationwide, population-based cohort study including patients >= 18 years with first-time acute pericarditis (n=12,381) during 1996-2020 was conducted. Ibuprofen use was modelled in two ways: First, we considered patients exposed based on the tablet strength of their first ibuprofen filling (a proxy for an intention-to-treat analysis). Second, we considered patients exposed in a time-varying manner (a proxy for an as-treated analysis). The primary outcome of major adverse cardiovascular events (MACE) was a composite of myocardial infarction, ischemic stroke, congestive heart failure, and cardiovascular death. Results: In the intention-to-treat analysis, the 1-year risk of MACE was 1.37% (95% confidence interval [CI]: 1.03-1.79) for ibuprofen initiators and 4.32% (95% CI: 3.89-4.78) for non-initiators. Compared with non-initiators within 1-year follow-up, the adjusted hazard ratio for MACE was 0.75 (95% CI: 0.67-0.85) for initiators overall, 0.38 (95% CI: 0.28-0.52) for initiators of >400 mg tablets, and 0.87 (95% CI: 0.76-0.99) for initiators of <= 400 mg tablets. In the as-treated analysis, compared with no use, the hazard ratio associated with ibuprofen use was 0.69 (95% CI: 0.54-0.89) for MACE, 0.82 (95% CI: 0.54-1.26) for myocardial infarction, 0.74 (95% CI: 0.45-1.22) for ischemic stroke, 0.67 (95% CI: 0.47-0.96) for congestive heart failure, and 0.60 (95% CI: 0.31-1.17) for cardiovascular death. Conclusion: Ibuprofen use for acute pericarditis was not associated with increased cardiovascular risks, supporting its safety in current practice.