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PURPOSE: Recent controversies on the safety profiles of opioids and paracetamol (acetaminophen) have led to changes in clinical guidance on osteoarthritis (OA) management. We studied the existing association between the use of different OA drug therapies and the risk for acute coronary events. METHODS: A cohort of patients with clinically diagnosed OA (according to ICD-10 codes) was identified in the SIDIAP database. Within the cohort, cases with incident acute coronary events (acute myocardial infarction or unstable angina) between 2008 and 2012 were identified using ICD-10 codes and data from hospital admission. Controls were matched 3:1 to acute coronary event-free patients matched by sex, age (±5 years), geographic area, and years since OA diagnosis (±2 years). Linked pharmacy dispensation data were used for assessing exposure to drug therapies. Multivariate conditional logistic regression models were fitted to estimate adjusted odds ratios of acute coronary events. FINDINGS: Totals of 5663 cases and 16,989 controls were studied. Previous morbidity and cardiovascular risk were higher in cases than in controls, with no significant differences in type or number of joints with OA. Multivariate adjusted analyses showed increased risks (odds ratio; 95% CI) related to the use of diclofenac (1.16; 1.06-1.27), naproxen (1.25; 1.04-1.48), and opioid analgesics (1.13; 1.03-1.24). No significant associations were observed with cyclooxygenase-2 selective NSAIDs, topical NSAIDs, glucosamine, chondroitin sulfate, paracetamol, or metamizole. IMPLICATIONS: In patients with clinically diagnosed OA, the use of nonselective NSAIDs or opioid analgesics is associated with an increased risk for acute coronary events. These risks should be considered when selecting treatments of OA in patients at high cardiovascular risk.

Original publication




Journal article


Clin ther

Publication Date





270 - 283


drug therapy, electronic health records, myocardial infarction, osteoarthritis, unstable angina, Acetaminophen, Adult, Aged, Aged, 80 and over, Analgesics, Analgesics, Opioid, Angina, Unstable, Anti-Inflammatory Agents, Non-Steroidal, Case-Control Studies, Cohort Studies, Female, Humans, Logistic Models, Male, Middle Aged, Myocardial Infarction, Odds Ratio, Osteoarthritis