Nonsteroidal anti-inflammatory drug use and risk of venous thromboembolism

Abstract

Background: The association between use of nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2-selective inhibitors (COX2Is) and risk of venous thromboembolism (VTE) remains unclear. Objectives: We examined this association. Patients/Methods: We conducted a population-based case-control study in northern Denmark (population 1.7 million). Using the National Patient Registry, we identified patients with a first hospital VTE diagnosis during 1999-2006 (n=8,368) and their comorbidities. For each case, we selected 10 controls (n=82,218) matched by age and sex. From the prescription database, we ascertained use of NSAIDs at the time of diagnosis (current use) or before (recent use), and co-medications. Current use was further classified as new use (first-ever prescription redemption within 60 days before diagnosis date) or long-term use. We used odds ratios from a logistic regression model to estimate incidence rate ratios (IRRs) with 95% confidence intervals (CIs). Results: Compared with no use, the adjusted IRR associating current nonselective NSAID use with VTE was 2.51 (95% CI 2.29-2.76) and 2.19 (95% CI 1.99-2.41) for current COX2I use. Recent users had substantially smaller increases than current users. The adjusted IRR among long-term users was 2.06 for nonselective NSAIDs (95% CI 1.85-2.29) and 1.92 for COX2Is (95% CI 1.72-2.15). Similarly increased risks were found for unprovoked VTE (occurrence in the absence of pregnancy, cancer, or major trauma, fracture, or surgery within 3 months preceding the VTE), deep venous thrombosis, pulmonary embolism, and individual NSAIDs. Conclusions: Use of nonselective NSAIDs or COX2Is was associated with two-fold or more increased risk of venous thromboembolism