{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:51:33Z","timestamp":1791669093187,"version":"4.3.4"},"reference-count":23,"publisher":"Scientific Scholar","content-domain":{"domain":["ijmr.org.in"],"crossmark-restriction":true},"short-container-title":["Indian J Med Res"],"abstract":"<jats:sec>\n<jats:title>Background &amp; objectives<\/jats:title>\n<jats:p>A few propensity-score-matched cohort studies have suggested increased cardiovascular events with gabapentinoids (gabapentin\/pregabalin). This systematic review analysed the cardiovascular safety of gabapentin and pregabalin in clinical practice.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Databases were searched for articles examining the occurrence of cardiovascular events with gabapentin and pregabalin in different clinical conditions. The primary outcome was to look at the occurrence of myocardial infarction (MI) and stroke. Secondary outcomes were to look at the occurrence of deep venous thrombosis (DVT), peripheral artery disease (PAD), pulmonary thrombo-embolism (PTE), heart failure (HF) and atrial fibrillation (AF).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Data from five cohort studies (10,85,488 patients) were analysed. Gabapentin use was associated with increased risk of MI after one year of [Hazard ratio (HR) 1.31(1.14,1.52); I<jats:sup>2<\/jats:sup>=0%; <jats:italic>P=<\/jats:italic>0.0002] use. Gabapentinoids were associated with increased risk of stroke after five years of use [HR 1.44 (1.04, 2.01); I<jats:sup>2<\/jats:sup>=86%; <jats:italic>P=<\/jats:italic>0.03]. Heart failure was not increased with the use of gabapentinoids. Their chronic use was associated with increased risk of PVD after one year [HR 1.41(1.18, 1.67); <jats:italic>P=<\/jats:italic>0.0001] and five years [HR 1.58 (1.16, 2.15); I<jats:sup>2<\/jats:sup>=83%; <jats:italic>P=<\/jats:italic>0.003] use. Gabapentinoid use was associated with increased risk of DVT after three months [HR 1.37(1.21, 1.55); <jats:italic>P&lt;<\/jats:italic>0.00001], one-year [HR 1.42 (1.15, 1.74); <jats:italic>P=<\/jats:italic>0.0009], and five years [HR 1.78 (1.31,2.40); I<jats:sup>2<\/jats:sup>=71%; <jats:italic>P=<\/jats:italic>0.0002] use. Their use was associated with increased risk of pulmonary embolism after three months [HR 1.27 (1.09, 1.46); <jats:italic>P=<\/jats:italic>0.002], one-year [HR 1.23 (1.01, 1.40); <jats:italic>P=<\/jats:italic>0.04], and five years of [HR 1.86 (1.64, 2.09); I<jats:sup>2<\/jats:sup>=0%; <jats:italic>P&lt;<\/jats:italic>0.0001] use.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Interpretation &amp; conclusions<\/jats:title>\n<jats:p>The use of gabapentinoids was associated with increased risks of thrombotic events as early as three months of use, and with increased risk of cardiovascular events on prolonged use of more than a year duration.<\/jats:p>\n<\/jats:sec>","DOI":"10.25259\/ijmr_1990_2024","type":"journal-article","created":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T06:19:14Z","timestamp":1748758754000},"page":"363-374","update-policy":"https:\/\/doi.org\/10.25259\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cardiovascular safety of gabapentinoids gabapentin &amp; pregabalin: A systematic review"],"prefix":"10.25259","volume":"161","author":[{"given":"Deep","family":"Dutta","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Centre for Endocrinology, Diabetes, Arthritis & Rheumatism (CEDAR) Superspeciality Healthcare, New Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritin","family":"Mohindra","sequence":"additional","affiliation":[{"name":"Department of Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoj","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Maharishi Markandeshwar Institute of Medical Sciences, Ambala, Haryana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mainak","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Ramakrishna Mission Seva Pratisthan Vivekananda Institute of Medical Sciences, Kolkata, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meha","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Centre for Endocrinology, Diabetes, Arthritis & Rheumatism (CEDAR) Superspeciality Healthcare, New Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satinath","family":"Mukhopadhyay","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Institute of Post Graduate Medical Education & Research, Kolkata, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10894","published-online":{"date-parts":[[2025,5,31]]},"reference":[{"key":"10.25259\/IJMR_1990_2024\/ref-1","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1080\/14737175.2016.1202764","article-title":"Alpha2delta ligands, gabapentin, pregabalin and mirogabalin: A review of their clinical pharmacology and therapeutic use","volume":"16","author":"Calandre","year":"2016","journal-title":"Expert Rev Neurother"},{"key":"10.25259\/IJMR_1990_2024\/ref-2","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1111\/add.13324","article-title":"Gabapentin misuse, abuse and diversion: A systematic review","volume":"111","author":"Smith","year":"2016","journal-title":"Addiction"},{"key":"10.25259\/IJMR_1990_2024\/ref-3","doi-asserted-by":"crossref","first-page":"2705","DOI":"10.3390\/cells12232705","article-title":"Effects of acute and chronic gabapentin treatment on cardiovascular function of rats","volume":"12","author":"Pendyala","year":"2023","journal-title":"Cells"},{"key":"10.25259\/IJMR_1990_2024\/ref-4","first-page":"33","article-title":"The mechanism of action of gabapentin in neuropathic pain","volume":"7","author":"Baillie","year":"2006","journal-title":"Curr Opin Investig Drugs"},{"key":"10.25259\/IJMR_1990_2024\/ref-5","doi-asserted-by":"crossref","first-page":"112807","DOI":"10.1016\/j.biopha.2022.112807","article-title":"Gabapentinoid-induced peripheral edema and acute heart failure: A translational study combining pharmacovigilance data and in vitro animal experiments","volume":"149","author":"Largeau","year":"2022","journal-title":"Biomed Pharmacother"},{"key":"10.25259\/IJMR_1990_2024\/ref-6","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1186\/s13256-023-03975-1","article-title":"Atrial fibrillation induced by gabapentin: a case report","volume":"17","author":"Park","year":"2023","journal-title":"J Med Case Rep"},{"key":"10.25259\/IJMR_1990_2024\/ref-7","first-page":"644","article-title":"A rare case of a gabapentin-induced cardiomyopathy","volume":"44","author":"Tellor","year":"2019","journal-title":"J Clin Pharm Ther"},{"key":"10.25259\/IJMR_1990_2024\/ref-8","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1186\/s12933-022-01610-9","article-title":"Cardiovascular risk of gabapentin and pregabalin in patients with diabetic neuropathy","volume":"21","author":"Pan","year":"2022","journal-title":"Cardiovasc Diabetol"},{"key":"10.25259\/IJMR_1990_2024\/ref-9","doi-asserted-by":"crossref","first-page":"e0307515","DOI":"10.1371\/journal.pone.0307515","article-title":"Association of adverse cardiovascular events with gabapentin and pregabalin among patients with fibromyalgia","volume":"19","author":"Pan","year":"2024","journal-title":"PLoS One"},{"key":"10.25259\/IJMR_1990_2024\/ref-10","doi-asserted-by":"crossref","first-page":"d5928","DOI":"10.1136\/bmj.d5928","article-title":"The Cochrane collaboration\u2019s tool for assessing risk of bias in randomised trials","volume":"343","author":"Higgins","year":"2011","journal-title":"BMJ"},{"key":"10.25259\/IJMR_1990_2024\/ref-11","doi-asserted-by":"crossref","first-page":"374","DOI":"10.3803\/EnM.2020.818","article-title":"Efficacy and safety of the novel dipeptidyl peptidase-4 inhibitor gemigliptin in the management of type 2 diabetes: A Meta-Analysis","volume":"36","author":"Dutta","year":"2021","journal-title":"Endocrinol Metab (Seoul)"},{"key":"10.25259\/IJMR_1990_2024\/ref-12","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1016\/j.dsx.2020.08.039","article-title":"Efficacy and safety of saroglitazar in managing hypertriglyceridemia in type-2 diabetes: A meta-analysis","volume":"14","author":"Dutta","year":"2020","journal-title":"Diabetes Metab Syndr"},{"key":"10.25259\/IJMR_1990_2024\/ref-13","doi-asserted-by":"crossref","first-page":"b2700","DOI":"10.1136\/bmj.b2700","article-title":"The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: Explanation and elaboration","volume":"339","author":"Liberati","year":"2009","journal-title":"BMJ"},{"key":"10.25259\/IJMR_1990_2024\/ref-14","doi-asserted-by":"crossref","first-page":"l4898","DOI":"10.1136\/bmj.l4898","article-title":"RoB 2: A revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"key":"10.25259\/IJMR_1990_2024\/ref-15","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/s10654-010-9491-z","article-title":"Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses","volume":"25","author":"Stang","year":"2010","journal-title":"Eur J Epidemiol"},{"key":"10.25259\/IJMR_1990_2024\/ref-16","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/S0140-6736(22)01472-6","article-title":"Comparison of amitriptyline supplemented with pregabalin, pregabalin supplemented with amitriptyline, and duloxetine supplemented with pregabalin for the treatment of diabetic peripheral neuropathic pain (OPTION-DM): a multicentre, double-blind, randomised crossover trial","volume":"400","author":"Tesfaye","year":"2022","journal-title":"Lancet"},{"key":"10.25259\/IJMR_1990_2024\/ref-17","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1016\/j.clinthera.2013.10.011","article-title":"Cardiac repolarization with Gabapentin enacarbil in a randomized, double-blind, placebo- and active-controlled, crossover thorough QT\/QTc study in healthy adults","volume":"35","author":"Davy","year":"2013","journal-title":"Clin Ther"},{"key":"10.25259\/IJMR_1990_2024\/ref-18","first-page":"37","article-title":"Real-world comparison of health care utilization between duloxetine and pregabalin initiators with fibromyalgia","volume":"7","author":"Peng","year":"2014","journal-title":"J Pain Res"},{"key":"10.25259\/IJMR_1990_2024\/ref-19","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1097\/AJP.0000000000001105","article-title":"Duloxetine, gabapentin, and the risk for acute myocardial infarction, stroke, and out-of-hospital death in medicare beneficiaries with non-cancer pain","volume":"39","author":"Corriere","year":"2023","journal-title":"Clin J Pain"},{"key":"10.25259\/IJMR_1990_2024\/ref-20","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1007\/s40264-018-0695-6","article-title":"Gabapentin and pregabalin and risk of atrial fibrillation in the elderly: A population-based cohort study in an electronic prescription database","volume":"41","author":"Ortiz de Landaluce","year":"2018","journal-title":"Drug Saf"},{"key":"10.25259\/IJMR_1990_2024\/ref-21","doi-asserted-by":"crossref","first-page":"110734","DOI":"10.1016\/j.diabres.2023.110734","article-title":"Morbidity and mortality of patients with diabetic neuropathy treated with pathogenetically oriented alpha-lipoic acid versus symptomatic pharmacotherapies - A nationwide database analysis from Hungary","volume":"201","author":"Jermendy","year":"2023","journal-title":"Diabetes Res Clin Pract"},{"key":"10.25259\/IJMR_1990_2024\/ref-22","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s11916-023-01126-1","article-title":"A brief review on the novel therapies for painful diabetic neuropathy","volume":"27","author":"Basem","year":"2023","journal-title":"Curr Pain Headache Rep"},{"key":"10.25259\/IJMR_1990_2024\/ref-23","doi-asserted-by":"crossref","first-page":"390","DOI":"10.21037\/apm-22-693","article-title":"Diabetic peripheral neuropathy essentials: A narrative review","volume":"12","author":"Chang","year":"2023","journal-title":"Ann Palliat Med"}],"container-title":["The Indian Journal of Medical Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ijmr.org.in\/cardiovascular-safety-of-gabapentinoids-gabapentin-pregabalin-a-systematic-review\/","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/ijmr.org.in\/cardiovascular-safety-of-gabapentinoids-gabapentin-pregabalin-a-systematic-review\/","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T06:19:17Z","timestamp":1748758757000},"score":1,"resource":{"primary":{"URL":"http:\/\/ijmr.org.in\/cardiovascular-safety-of-gabapentinoids-gabapentin-pregabalin-a-systematic-review\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,31]]},"references-count":23,"alternative-id":["10.25259\/IJMR_1990_2024"],"URL":"https:\/\/doi.org\/10.25259\/ijmr_1990_2024","relation":{},"ISSN":["0971-5916"],"issn-type":[{"value":"0971-5916","type":"print"}],"subject":[],"published":{"date-parts":[[2025,5,31]]},"article-number":"363"}}