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.
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. doi: 10.1503/cmaj.190339.
Allopurinol 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.
We 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.
Among 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.
Heart 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.
别嘌醇常用于痛风治疗，随着评估其潜在心肾获益的临床试验不断开展，其临床应用可能会扩大。由于心脏病被认为是别嘌醇相关性严重皮肤不良反应的一个危险因素，我们试图在加拿大一般人群队列中证实这种关联。
我们利用加拿大不列颠哥伦比亚省的人群数据，确定了 1997 年至 2015 年间所有别嘌醇新使用者。我们研究了心脏病（缺血性心脏病和心力衰竭）与严重皮肤不良反应住院风险之间的关系，并对已知和推测的危险因素进行了调整。我们还评估了联合临床和人口统计学危险因素的共同作用。
在 130325 例别嘌醇初始使用者中，有 109 例因别嘌醇相关性严重皮肤不良反应住院。患有心脏病的患者的多变量相对风险为 1.55（95%置信区间 1.01-2.37）。患有心脏病和慢性肾脏病且起始剂量大于 100mg/d 的患者风险增加 11 倍。患有心脏病和慢性肾脏病的患者起始低剂量别嘌醇会使风险降低 5 倍。来自亚洲人口较多地区的患有心脏病的老年女性比来自其他地区无心脏病的年轻男性的别嘌醇相关性严重皮肤不良反应风险高 23 倍。
心脏病与别嘌醇相关性严重皮肤不良反应的风险独立相关，与慢性肾脏病相似，低剂量别嘌醇起始治疗可能会大大降低这种风险。在开始使用别嘌醇时，应考虑这些罕见但严重的不良反应的危险因素。
