• Chio Yokose, Na Lu, Hui Xie, Lingyi Li, Yufei Zheng, Natalie McCormick, Sharan K Rai, J Antonio Aviña-Zubieta, and Hyon K Choi.
• Division of Rheumatology, Allergy and Immunology (Yokose, McCormick, Choi), Massachusetts General Hospital, Boston, Mass.; Arthritis Research Canada (Lu, Xie, Li, Zheng, McCormick, Rai, Aviña-Zubieta, Choi), Richmond, BC; Faculty of Health Sciences (Xie), Simon Fraser University, Burnaby, BC; Division of Rheumatology (Aviña-Zubieta), University of British Columbia, Vancouver, BC.
• CMAJ. 2019 Sep 30; 191 (39): E1070-E1077.

BackgroundAllopurinol is commonly prescribed for gout, and its clinical use may expand with ongoing trials assessing its potential cardiorenal benefits. Because heart disease has been suggested to be a risk factor for allopurinol-associated severe cutaneous adverse reactions, we sought to confirm this association in a Canadian general population cohort.MethodsWe used population data from British Columbia, Canada, to identify all incident allopurinol users between 1997 and 2015. We examined the association between heart disease (ischemic heart disease and heart failure) and the risk of hospital admission for severe cutaneous adverse reactions, adjusting for known and purported risk factors. We also evaluated the joint effects of combined clinical and demographic risk factors.ResultsAmong 130 325 allopurinol initiators, 109 hospital admissions occurred for allopurinol-associated severe cutaneous adverse reactions. The multivariable relative risk among those with heart disease was 1.55 (95% confidence interval 1.01-2.37). Patients with heart disease and chronic kidney disease who were started on an allopurinol dosage of greater than 100 mg/d had an 11-fold higher risk. Allopurinol initiation at a lower dosage among patients with heart disease and chronic kidney disease resulted in a fivefold reduction in risk. Older women with heart disease from regions with large Asian populations had a 23-fold higher risk of allopurinol-associated severe cutaneous adverse reactions than younger men without heart disease from other regions.InterpretationHeart disease is independently associated with risk of allopurinol-associated severe cutaneous adverse reactions, similar to chronic kidney disease, and low-dosage allopurinol initiation may substantially mitigate this risk. Risk factors for these rare but serious reactions should be considered when initiating allopurinol.© 2019 Joule Inc. or its licensors.

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