{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T00:01:32Z","timestamp":1793404892161,"version":"4.5.0"},"reference-count":41,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"<jats:sec id=\"ab-zoi250698-4\"><jats:title>Importance<\/jats:title><jats:p>Both pregabalin and gabapentin are common nonopioid medications used to treat chronic pain, which affects up to 30% of patients. Because pregabalin has greater potency than gabapentin in binding to the \u03b12\u03b4 subunit of the L-type calcium channel, pregabalin may be associated with an increased risk for heart failure (HF).<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi250698-5\"><jats:title>Objective<\/jats:title><jats:p>To compare incident hospitalizations and emergency department (ED) visits for HF among new users of pregabalin vs gabapentin among Medicare beneficiaries with noncancer chronic pain.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi250698-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This retrospective cohort study included data collected between January 1, 2015, and December 21, 2018, for Medicare beneficiaries aged 65 to 89 years with chronic noncancer pain and without a history of HF and terminal illnesses. Data were analyzed from March 21 to December 2, 2024.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi250698-7\"><jats:title>Exposure<\/jats:title><jats:p>New use of pregabalin or gabapentin.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi250698-8\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>The primary outcome was hospital admission or ED visit with a primary discharge diagnosis of HF. Secondary outcomes were incidence of outpatient HF diagnosis and all-cause mortality. Adjusted hazard ratios (AHRs) were calculated using inverse probability of treatment weighting propensity score adjustment accounting for 231 covariates, including demographic, clinical, and health care utilization variables and medication use.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi250698-9\"><jats:title>Results<\/jats:title><jats:p>The cohort included 246 237 Medicare beneficiaries, of whom 18 622 (7.6%) were new users of pregabalin and 227\u202f615 (92.4%) were new users of gabapentin; the cohort was predominantly female (66.8%), with a median age of 73 years (IQR, 69-78 years). During 114\u202f113 person-years of follow-up, 1470 patients had a hospital admission or ED visit for HF. The rate of HF was 18.2 (95% CI, 15.3-21.6) per 1000 person-years for pregabalin and 12.5 (95% CI, 11.9-13.2) per 1000 person-years for gabapentin (AHR, 1.48 [95% CI, 1.19-1.77]). When restricted to patients with a history of cardiovascular disease, pregabalin was associated with an elevated HF risk compared with gabapentin (AHR, 1.85 [95% CI, 1.38-2.47]). Increased risk of outpatient HF incidence was also noted among patients receiving pregabalin compared with those receiving gabapentin (AHR, 1.27 [95% CI, 1.02-1.58]). All-cause mortality was not significantly different between groups (AHR, 1.26 [95% CI, 0.95-1.76]).<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi250698-10\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>In this retrospective cohort study of Medicare beneficiaries with chronic noncancer pain, incident HF was increased in new users of pregabalin compared with new users of gabapentin. These findings should be considered, especially in patients with a history of cardiovascular disease.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.24451","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T15:30:37Z","timestamp":1754062237000},"page":"e2524451","source":"Crossref","is-referenced-by-count":11,"title":["Initiation of Pregabalin vs Gabapentin and Development of Heart Failure"],"prefix":"10.1001","volume":"8","author":[{"given":"Elizabeth E.","family":"Park","sequence":"first","affiliation":[{"name":"Department of Medicine, Columbia University Irving Medical Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura L.","family":"Daniel","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Miami and Miami VA Healthcare System, Miami, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyson L.","family":"Dickson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"},{"name":"Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee"},{"name":"Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee"},{"name":"Department of Health Policy, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan","family":"Corriere","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"},{"name":"Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee"},{"name":"Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee"},{"name":"Department of Health Policy, Vanderbilt University Medical Center, Nashville, Tennessee"},{"name":"Vertex Pharmaceuticals, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puran","family":"Nepal","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Miami and Miami VA Healthcare System, Miami, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathi","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"},{"name":"Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee"},{"name":"Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee"},{"name":"Department of Health Policy, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Dale","family":"Plummer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"},{"name":"Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee"},{"name":"Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee"},{"name":"Department of Health Policy, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William D.","family":"Dupont","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"},{"name":"Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee"},{"name":"Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee"},{"name":"Department of Health Policy, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine T.","family":"Murray","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee"},{"name":"Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee"},{"name":"Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee"},{"name":"Department of Health Policy, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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DA. Gabapentin differs from pregabalin in several key ways. Pharmacy Times. October 14, 2024. Accessed November 27, 2024. https:\/\/www.pharmacytimes.com\/view\/how-gabapentin-differs-from-pregabalin"},{"key":"zoi250698r12","unstructured":"Lyrica. European Medicines Agency. March 17, 2023. Accessed April 23, 2025. https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/lyrica"},{"key":"zoi250698r18","unstructured":"Welcome to the Chronic Conditions Data Warehouse. Centers for Medicare & Medicaid Services. Accessed April 23, 2025. https:\/\/www2.ccwdata.org\/web\/guest\/home\/"},{"key":"zoi250698r19","unstructured":"Medicare program\u2014general information. Centers for Medicare & Medicaid Services. Accessed April 23, 2025. https:\/\/www.cms.hhs.gov\/MedicareGenInfo\/"},{"key":"zoi250698r20","unstructured":"Prescription drug coverage\u2014general information. Centers for Medicare & Medicaid Services. 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