{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T16:36:52Z","timestamp":1773679012424,"version":"3.50.1"},"reference-count":32,"publisher":"American Medical Association (AMA)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Hydralazine is a selectively used cardiovascular medication with case reports and case series demonstrating an association between the use of hydralazine and antineutrophil cytoplasmic antibody\u2013associated vasculitis.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To assess the risk of vasculitis associated with hydralazine use compared with use of an angiotensin-converting enzyme inhibitor (ACE) or angiotensin receptor blocker (ARB).<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This population-based, retrospective cohort study assessed adults 66 years or older from Ontario, Canada, who were newly prescribed hydralazine from January 1, 2008, to December 31, 2021. Data analysis was performed from May to August 2025.<\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n Newly dispensed hydralazine in an outpatient setting.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n \n The main outcome was a diagnosis of vasculitis using\n International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10)<\/jats:italic>\n codes. Overlap-weighted Cox proportional hazards regression was used to examine the association between hydralazine use (active comparator: ACE or ARB) with new-onset vasculitis.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Of a total of 583\u202f136 eligible adults (mean [SD] age, 73.0 [7.2] years; 51 827 [55.2%] female), 40\u202f748 individuals were dispensed hydralazine and 542\u202f388 an ACE or ARB. Hydralazine use compared with ACE or ARB use was associated with a higher risk of vasculitis during follow-up (hydralazine: 328 events [0.8%]; ACE or ARB: 2712 events [0.5%]; absolute risk difference, 0.3 percentage points; hazard ratio, 1.19; 95% CI, 1.04-1.37). Results were no longer significant when accounting for the competing risk of death.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this cohort study of adults who were newly prescribed hydralazine, vasculitis associated with hydralazine was rare, despite multiple reported cases. Use of hydralazine is unlikely to be associated with a clinically meaningful increased risk of vasculitis.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.1943","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T15:30:38Z","timestamp":1773675038000},"page":"e261943","source":"Crossref","is-referenced-by-count":0,"title":["Hydralazine Use and Risk of Vasculitis"],"prefix":"10.1001","volume":"9","author":[{"given":"Deena","family":"Fremont","sequence":"first","affiliation":[{"name":"Ottawa Hospital Research Institute, Ottawa, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan","family":"Dhaliwal","sequence":"additional","affiliation":[{"name":"Ottawa Hospital Research Institute, Ottawa, Ontario, Canada"},{"name":"ICES uOttawa, Ottawa, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Canney","sequence":"additional","affiliation":[{"name":"Ottawa Hospital Research Institute, Ottawa, Ontario, Canada"},{"name":"Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayub","family":"Akbari","sequence":"additional","affiliation":[{"name":"Ottawa Hospital Research Institute, Ottawa, Ontario, Canada"},{"name":"Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory L.","family":"Hundemer","sequence":"additional","affiliation":[{"name":"Ottawa Hospital Research Institute, Ottawa, Ontario, Canada"},{"name":"ICES uOttawa, Ottawa, Ontario, Canada"},{"name":"Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vimal K.","family":"Derebail","sequence":"additional","affiliation":[{"name":"UNC Kidney Center, Division of Nephrology and Hypertension, University of North Carolina at Chapel Hill, Chapel Hill"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manish M.","family":"Sood","sequence":"additional","affiliation":[{"name":"Ottawa Hospital Research Institute, Ottawa, Ontario, Canada"},{"name":"Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Massicotte-Azarniouch","sequence":"additional","affiliation":[{"name":"Ottawa Hospital Research Institute, Ottawa, Ontario, Canada"},{"name":"Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"10","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"issue":"1","key":"zoi260090r1","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/1479-5876-4-10","article-title":"Hydralazine target: from blood vessels to the epigenome.","volume":"4","author":"Arce","year":"2006","journal-title":"J Transl Med"},{"issue":"8","key":"zoi260090r2","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1093\/eurjhf\/hfs105","article-title":"ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012.","volume":"14","author":"McMurray","year":"2012","journal-title":"Eur J Heart Fail"},{"issue":"3","key":"zoi260090r3","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1002\/ehf2.12421","article-title":"Underuse of hydralazine and isosorbide dinitrate for heart failure in patients of African ancestry: a cross-European survey.","volume":"6","author":"Brewster","year":"2019","journal-title":"ESC Heart Fail"},{"key":"zoi260090r4","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.ijcard.2015.05.160","article-title":"Hydralazine and nitrates alone or combined for the management of chronic heart failure: a systematic review.","volume":"196","author":"Farag","year":"2015","journal-title":"Int J Cardiol"},{"issue":"2","key":"zoi260090r5","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.semarthrit.2018.01.005","article-title":"Hydralazine-associated vasculitis: overlapping features of drug-induced lupus and vasculitis.","volume":"48","author":"Kumar","year":"2018","journal-title":"Semin Arthritis Rheum"},{"key":"zoi260090r6","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2018-227161","article-title":"Hydralazine-associated antineutrophil cytoplasmic antibody vasculitis with pulmonary\u2013renal syndrome.","author":"Aeddula","journal-title":"BMJ Case Rep"},{"issue":"5","key":"zoi260090r7","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1056\/NEJM199108013250502","article-title":"A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure.","volume":"325","author":"Cohn","year":"1991","journal-title":"N Engl J Med"},{"issue":"24","key":"zoi260090r8","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1056\/NEJM198606123142404","article-title":"Effect of vasodilator therapy on mortality in chronic congestive heart failure: results of a Veterans Administration Cooperative Study.","volume":"314","author":"Cohn","year":"1986","journal-title":"N Engl J Med"},{"issue":"20","key":"zoi260090r9","doi-asserted-by":"publisher","first-page":"2049","DOI":"10.1056\/NEJMoa042934","article-title":"Combination of isosorbide dinitrate and hydralazine in blacks with heart failure.","volume":"351","author":"Taylor","year":"2004","journal-title":"N Engl J Med"},{"issue":"8","key":"zoi260090r10","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1001\/jamainternmed.2019.0631","article-title":"Risk of hospitalization for serious adverse gastrointestinal events associated with sodium polystyrene sulfonate use in patients of advanced age.","volume":"179","author":"Noel","year":"2019","journal-title":"JAMA Intern Med"},{"issue":"5","key":"zoi260090r12","doi-asserted-by":"publisher","first-page":"S31","DOI":"10.4103\/sja.SJA_543_18","article-title":"The STROBE guidelines.","volume":"13","author":"Cuschieri","year":"2019","journal-title":"Saudi J Anaesth"},{"issue":"2","key":"zoi260090r13","first-page":"67","article-title":"Coding accuracy of administrative drug claims in the Ontario Drug Benefit database.","volume":"10","author":"Levy","year":"2003","journal-title":"Can J Clin Pharmacol"},{"issue":"7","key":"zoi260090r14","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1038\/nrrheum.2015.30","article-title":"Active-comparator design and new-user design in observational studies.","volume":"11","author":"Yoshida","year":"2015","journal-title":"Nat Rev Rheumatol"},{"key":"zoi260090r15","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kez059.016","article-title":"Utilization of Canadian Healthcare Administrative databases to accurately identify cases of ANCA-associated vasculitis.","author":"Garner","year":"2020","journal-title":"Rheumatology (Oxford)"},{"issue":"23","key":"zoi260090r16","doi-asserted-by":"publisher","first-page":"2417","DOI":"10.1001\/jama.2020.7819","article-title":"Overlap weighting.","volume":"323","author":"Thomas","year":"2020","journal-title":"JAMA"},{"issue":"4","key":"zoi260090r17","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1093\/ckj\/sfab229","article-title":"Association of anti-neutrophil cytoplasmic antibody-associated vasculitis and cardiovascular events: a population-based cohort study.","volume":"15","author":"Massicotte-Azarniouch","year":"2021","journal-title":"Clin Kidney J"},{"issue":"25","key":"zoi260090r18","doi-asserted-by":"crossref","first-page":"3083","DOI":"10.1002\/sim.3697","article-title":"Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples.","volume":"28","author":"Austin","year":"2009","journal-title":"Stat Med"},{"issue":"2","key":"zoi260090r19","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1002\/1529-0131(200002)43:2<405::AID-ANR22>3.0.CO;2-5","article-title":"Drug-associated antineutrophil cytoplasmic antibody-positive vasculitis: prevalence among patients with high titers of antimyeloperoxidase antibodies.","volume":"43","author":"Choi","year":"2000","journal-title":"Arthritis Rheum"},{"issue":"2","key":"zoi260090r20","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.kint.2021.03.029","article-title":"Anti-neutrophil cytoplasmic antibody associated glomerulonephritis complicating treatment with hydralazine.","volume":"100","author":"Santoriello","year":"2021","journal-title":"Kidney Int"},{"issue":"2","key":"zoi260090r21","doi-asserted-by":"crossref","first-page":"182","DOI":"10.2174\/1573403X16666200518092814","article-title":"Hydralazine-induced ANCA associated vasculitis (AAV) presenting with pulmonary-renal syndrome (PRS): a case report with literature review.","volume":"17","author":"Doughem","year":"2021","journal-title":"Curr Cardiol Rev"},{"issue":"8","key":"zoi260090r22","doi-asserted-by":"crossref","first-page":"745","DOI":"10.3109\/08860220903118590","article-title":"Hydralazine-induced ANCA-positive pauci-immune glomerulonephritis: a case report and literature review.","volume":"31","author":"Dobre","year":"2009","journal-title":"Ren Fail"},{"issue":"8","key":"zoi260090r23","doi-asserted-by":"crossref","DOI":"10.1172\/JCI178813","article-title":"Sequential carbonyl derivatives and hydrazone adduct formation on myeloperoxidase contribute to development of ANCA vasculitis.","volume":"135","author":"Xi","year":"2025","journal-title":"J Clin Invest"},{"issue":"22","key":"zoi260090r24","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1056\/NEJM198806023182209","article-title":"Drug-related lupus.","volume":"318","author":"Hess","year":"1988","journal-title":"N Engl J Med"},{"issue":"2","key":"zoi260090r25","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.kint.2021.03.029","article-title":"Anti-neutrophil cytoplasmic antibody associated glomerulonephritis complicating treatment with hydralazine.","volume":"100","author":"Santoriello","year":"2021","journal-title":"Kidney Int"},{"issue":"11","key":"zoi260090r26","doi-asserted-by":"crossref","first-page":"2670","DOI":"10.1093\/ndt\/gft355","article-title":"When do we need competing risks methods for survival analysis in nephrology?","volume":"28","author":"Noordzij","year":"2013","journal-title":"Nephrol Dial Transplant"},{"issue":"1","key":"zoi260090r32","first-page":"81","article-title":"Cutaneous vasculitis secondary to ramipril.","volume":"3","author":"Gupta","year":"2004","journal-title":"J Drugs Dermatol"},{"key":"zoi260090r11","unstructured":"Statistics Canada. Population estimates on July 1, by age and gender. 2024. Accessed January 27, 2026. https:\/\/www150.statcan.gc.ca\/t1\/tbl1\/en\/tv.action?pid=1710000501"},{"key":"zoi260090r27","unstructured":"Electronic Medicines Compendium. Lenalidomide Sandoz 5 mg hard capsules. Accessed January 27, 2026. https:\/\/www.medicines.org.uk\/emc\/product\/14127\/smpc"},{"key":"zoi260090r28","unstructured":"Accord Healthcare. SmPC - Hydralazine 25mg tablets BP: change history. Accessed January 27, 2026. https:\/\/accord-healthcare-products.co.uk\/document\/smpc-hydralazine-tablets-bp-25mg\/changes?back=hydralazine-tablets"},{"key":"zoi260090r29","unstructured":"US Food and Drug Administration. Hydralazine hydrochloride injection. Accessed January 27, 2026. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2013\/040136s005lbl.pdf"},{"key":"zoi260090r30","unstructured":"Health Canada. Product information: kidney and blood PWR. Accessed January 27, 2026. https:\/\/health-products.canada.ca\/dpd-bdpp\/info?lang=eng&code=2498"},{"key":"zoi260090r31","unstructured":"SteriMax Inc. Product Monograph: Apresoline (Hydralazine Hydrochloride USP). 2016. Accessed January 27, 2026. https:\/\/sterimaxinc.com\/wp-content\/uploads\/2016\/03\/1.3.1-SteriMax-English-PM-February-8-20162.pdf"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2846501\/fremont_2026_oi_260090_1773073665.05824.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T15:30:43Z","timestamp":1773675043000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2846501"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,16]]},"references-count":32,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3,2]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2026.1943","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,16]]}}}