2 0 2 6 C O M P E N D I U M O F F E D E R A L M E D I C I N E 5 9 analgesic in over two decades. Current studies have shown that suzetrig- ine has potential in treat- ing acute pain periop- eratively for minimally to moderately painful ambu- latory procedures.”4 A study published earlier this year in Clinical Pharmacology & Therapeutics reminded clinicians that nonopioid painkillers aren’t always a panacea. Researchers from the University of Miami, the Miami VA Healthcare System, Vanderbilt University Medical Center and the VA Tennessee Valley Healthcare System in Nashville, TN, discussed potential concerns with pre- gabalin and duloxetine, widely prescribed non-opioid medications for chronic musculoskeletal pain.5 The researchers noted that pregabalin might increase the risk of heart failure, and duloxetine increases heart rate and blood pressure. Yet, little has been understood about their comparative cardiovascular safety. That led to a study comparing cardiovascular outcomes between new users of pregabalin and new users of duloxetine among U.S. veterans with chronic musculoskeletal conditions. The study team conducted a retrospective cohort study of veterans with chronic noncancer musculoskel- etal pain who started pregabalin or duloxetine between 2015 and 2021. Defined as the primary outcome was a major adverse cardiovascular event (MACE), a com- posite of acute myocardial infarction (AMI), stroke, heart failure (HF) or cardiovascular death. CV events were identified through VA records and linked data from Medicare and the National Death Index. The study included 26,684 new users of prega- balin and 152,808 new users of duloxetine (83% male, 69% reported white race, median age = 56 years). During a total follow-up of 141,112 person-years, 1,798 total MACE events were reported. Results sug- gested that the rate of MACE was higher for pregaba- lin users compared to duloxetine users (unadjusted HR: 1.61 (95% CI: 1.43-1.81), adjusted HR: 1.24 (95% CI: 1.08-1.41)), driven by higher rates of HF and AMI among pregabalin users. “These findings present new considerations regard- ing the comparative cardiovascular safety of therapeutic options for chronic musculoskeletal pain,” the authors wrote. 1 LaRowe LR, Goetzinger A, Fox K, Kilpatrick R. Pass legislation to expand access to nonopioid pain treatments among older adults. Transl Behav Med. 2025 Jan 16;15(1):ibaf048. doi: 10.1093/tbm/ibaf048. PMID: 40966457. 2Ozkaya B, Ozturk GA, Akman C, Erturk N, Ekingen E, Karcioglu O. The Characteristics of Centrally Acting Non-opioid Analgesics in the Management of Acute Pain and Neuropathic Pain Syndromes. Curr Pharm Des. 2026 Mar 18. doi: 10.2174/0113816128428513260121185400. Epub ahead of print. PMID: 41937523. 3Chen, SL, Liu, MA, Swisher, MW.. Suzetrigine, a selective NaV1.8 inhibitor in acute and chronic pain: mechanistic insights, clinical outcomes, and future perspectives. Current Opinion in Anesthesiology 39(2):p 183-187, April 2026. | DOI: 10.1097/ACO.0000000000001599 4Pham A, Yep H, Wozniak S, Javvaji A, Nada E, Bergese S. Beyond Opioids: A Review of Suzetrigine for Acute Pain Management. Inter- national Journal of Molecular Sciences. 2025; 26(20):9865. https://doi. org/10.3390/ijms26209865 5Campbell S, Nepal P, Daniel L, Wilson O, et. Al. Association of Pre- gabalin vs. Duloxetine with Cardiovascular Events: A Retrospective Cohort Study Among US Veterans With Chronic Musculoskeletal Pain. Clin Pharmacol Ther. 2026 Apr;119(4):1088-1094. doi: 10.1002/ cpt.70215. Epub 2026 Feb 4. PMID: 41640183; PMCID: PMC12997501. Three Waves of Opioid Overdose Deaths Source: CDC
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