Background/Purpose: Pregabalin and duloxetine are among the most prescribed non-opioid medications for patients with chronic pain. Pregabalin may raise the risk for heart failure, and duloxetine increases heart rate and blood pressure; however, little is known about their comparative cardiovascular safety. This study aimed to compare cardiovascular outcomes between new users of pregabalin and duloxetine in US Veterans with chronic musculoskeletal conditions.

Methods: This was a retrospective cohort study of US Veterans, ages 18-89 years, with chronic non-cancer musculoskeletal pain who were new users of pregabalin or duloxetine between 2014 and 2021. We excluded Veterans who were in long-term care or hospice, hospitalized for a month or more, and afflicted with serious illnesses in the year before their first prescription. The primary outcome was a major adverse cardiovascular event (MACE) – a composite of acute myocardial infarction, stroke, congestive heart failure, or cardiac death. For mortality causes, we used data from the National Death Index. For cardiac events, we used Veterans Affairs (VA) data and linked Medicare data. We created a propensity score using 153 covariates from ICD codes based on literature review and past studies and used it to adjust for confounding with inverse probability of treatment weighting (IPTW). Cox proportional hazard regression model was used to analyze outcomes over time.

Results: This study included 26,684 new users of pregabalin and 152,808 new users of duloxetine. The cohort was predominantly male (83%) and of reported White race (70%). The median age was 56 years old for both medications (IQR:44-67 for pregabalin, 42-67 for duloxetine). Prior to IPTW, rates of neuropathic pain, diabetes, and hypertension were higher among users of pregabalin, whereas rates of stress and anxiety were higher in users of duloxetine. Following IPTW, all covariates were balanced, indicated by standardized differences of less than one percent. During the study period, there were 1,798 MACE events. Follow-up time was 17,978 patient-years for pregabalin users and 123,134 patient-years for duloxetine users. The rate of MACE was higher for pregabalin users when compared to duloxetine users [unadjusted HR: 1.61 (CI: 1.43, 1.81), adjusted HR: 1.23 (CI: 1.08, 1.40)]. These differences were explained by higher rates of congestive heart failure and acute myocardial infarction among pregabalin users compared to duloxetine users.

Conclusion: In this retrospective cohort study of US Veterans ages 18-89 with chronic non-cancer musculoskeletal pain, new users of pregabalin had an increased risk of heart failure and acute myocardial infarction compared to new users of duloxetine.

Rates of cardiovascular outcomes in new users of pregabalin vs duloxetine

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/risk-of-cardiovascular-events-is-higher-in-pregabalin-users-versus-duloxetine-a-cohort-study-among-veterans-with-chronic-musculoskeletal-pain/