Abstract
OBJECTIVE: Duloxetine, an antidepressant commonly used as a nonopioid analgesic for chronic pain management, has been speculated to increase cardiovascular (CV) complications. This study aims to evaluate the CV and mortality risks associated with duloxetine compared to gabapentin in patients with hip osteoarthritis (OA). METHODS: In this population-based, retrospective cohort study using Korean health insurance data (2013-2022), we evaluated the cardiovascular risk of duloxetine versus gabapentin in patients with hip osteoarthritis, applying inverse probability of treatment weighting (IPTW) with adjustment methods, with outcomes included composite cardiovascular events, major cardiovascular events (MACE), stroke, heart failure, and acute myocardial infarction (AMI). RESULTS: A total of 3383 and 18,874 patients were included in the duloxetine and gabapentin groups, respectively, with a mean follow-up of 4.1 years. The composite outcomes risk was higher with duloxetine than with gabapentin (HR 1.10; 95% CI, 1.03-1.17). Duloxetine was associated with increased risk of MACE (HR 1.15; 95% CI, 1.06-1.27), hemorrhagic stroke (HR 1.52; 95% CI, 1.23-1.86), and heart failure (HR 1.19; 95% CI, 1.05-1.34), whereas a lower risk was observed for AMI (HR 0.65, 95% CI, 0.52-0.82). In our subgroup analysis of patients with no baseline cardiovascular diseases (CVDs), duloxetine users had a higher likelihood of experiencing composite outcomes (HR 1.29), MACE (1.41), hemorrhagic stroke (HR 1.79), ischemic stroke (HR 1.18), and heart failure (HR 1.44) compared to gabapentin users. CONCLUSION: Duloxetine was generally associated with increased CV risks, while a lower risk of AMI and no significant increase in mortality were observed compared to gabapentin. Our subgroup analysis further suggests that when potential confounding from preexisting CVDs was minimized, duloxetine was associated with incident CV complications in patients without prior CVDs.