What is the clinical evidence from this study?

Study design: Cohort. Population: Hip Osteoarthritis (n=22257). Intervention: Duloxetine vs. Gabapentin. Primary outcome: Composite cardiovascular events (all-cause death, cardiac death, AMI, stroke, arrhythmia, heart failure) (HR 1.10, 95% CI 1.03-1.17, p=0.03).

December 1, 2025Journal of Pain Research1 citationsOpen Access

Comparative Cardiovascular Safety of Duloxetine and Gabapentin in Patients with Hip Osteoarthritis

Q: What does this research mean for the field?

Duloxetine increases the risk of composite cardiovascular events by 10% compared to gabapentin in patients with hip osteoarthritis. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

SMSuhyeon MoonKangbuk Samsung Hospital ECEunjung ChooAjou University YCYeo Jin ChoiKyung Hee University

Key Result

Duloxetine increased the risk of composite cardiovascular events by 10% compared to gabapentin in patients with hip osteoarthritis (HR 1.10).

Study Design

Type

Cohort (n=22,257)

Structured PICO

Does duloxetine increase the risk of cardiovascular events compared to gabapentin in patients with hip osteoarthritis?

Population

22,257 adult patients (aged 20-85 years) with hip osteoarthritis (n=3,383 in duloxetine group, n=18,874 in gabapentin group), mean age ~63.5 years, ~62% female, based in South Korea. Key exclusions: psychiatric disorders at baseline, end-stage renal disease, and metastatic cancer.

Intervention

Duloxetine newly initiated for osteoarthritis pain management

Comparator

Gabapentin newly initiated for osteoarthritis pain management

Outcome

Composite of all-cause death, cardiac death, new-onset acute myocardial infarction, stroke (both ischemic and hemorrhagic), arrhythmia, and heart failurecomposite

In patients with hip osteoarthritis, duloxetine use for pain management is associated with a modestly increased risk of composite cardiovascular events, including heart failure and hemorrhagic stroke, compared to gabapentin.

Main Result

Effect estimate: HR 1.10 (95% CI 1.03-1.17)

Absolute Event Rate: 2.16% vs 2.03%

p-value: p=0.03

Limitations

Focus on hip OA patients limits generalizability to other populations and indications
Residual confounding may exist despite IPTW and adjustments
Reliance on ICD-10 diagnosis codes may lead to over- or under-estimation of outcome events
Exclusion of psychiatric comorbidities limits generalizability to other OA populations

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.

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