Singh Jasvinder A, Cleveland John
Medicine Service, Birmingham VA Medical Center, Birmingham, AL, USA.
Department of Medicine at School of Medicine, and Division of Epidemiology at School of Public Health, University of Alabama at Birmingham (UAB), Birmingham, AL, USA.
BMC Med. 2017 Mar 22;15(1):59. doi: 10.1186/s12916-017-0816-6.
There are no published human studies investigating whether the use of allopurinol, the most commonly used medication for the treatment of hyperuricemia in gout, the most common type of inflammatory arthritis in adults, has any beneficial effects on ventricular electrophysiology. The objective of our study was to assess whether allopurinol use is associated with a reduction in the risk of ventricular arrhythmias (VA).
We used the 5% random sample of Medicare beneficiaries from 2006-2012 to examine new allopurinol use and the risk of incident VA. Multivariable Cox regression analyses were adjusted for demographics (age, race, sex), comorbidity, cardiac medications, and conditions associated with VA. We calculated hazard ratios (HR) and 95% confidence intervals (CI).
Of the 28,755 episodes of new allopurinol use, 2538 were associated with incident VA (8.8%). Among patients with incident VA, 54% were male, 78% were White, 75% had gout as the underlying diagnosis, and the mean Charlson-Romano comorbidity score was 4.8. The crude incidence of VA per 1,000,000 person-days declined as the duration of allopurinol use increased: 1-180 days, 151; 181 days to 2 years, 105; and > 2 years, 85. In multivariable-adjusted analyses, compared to non-use, allopurinol use was associated with lower HR of VA of 0.82 (95% CI, 0.76-0.90). Compared to allopurinol non-use, longer allopurinol use durations were significantly associated with lower multivariable-adjusted HR for VA: 1-180 days, 0.96 (95% CI, 0.85-1.08); 181 days to 2 years, 0.76 (95% CI, 0.68-0.85); and > 2 years, 0.72 (95% CI, 0.60-0.87). Multiple sensitivity analyses adjusting for cardiac conditions, anti-arrhythmic drugs and alternate definitions confirmed our findings with minimal/no attenuation of estimates.
Allopurinol use and use duration of more than 6 months were independently associated with a lower risk of VA. Future studies need to assess the pathophysiology of this potential benefit.
痛风是成年人中最常见的炎症性关节炎类型，别嘌醇是治疗痛风性高尿酸血症最常用的药物。目前尚无已发表的人体研究调查使用别嘌醇是否对心室电生理有任何有益影响。我们研究的目的是评估使用别嘌醇是否与降低室性心律失常（VA）风险相关。
我们使用了2006 - 2012年医疗保险受益人的5%随机样本，以研究新使用别嘌醇情况和发生VA的风险。多变量Cox回归分析针对人口统计学特征（年龄、种族、性别）、合并症、心脏药物以及与VA相关的情况进行了调整。我们计算了风险比（HR）和95%置信区间（CI）。
在28755例新使用别嘌醇的病例中，2538例与发生VA相关（8.8%）。在发生VA的患者中，54%为男性，78%为白人，75%的潜在诊断为痛风，Charlson - Romano合并症平均评分为4.8。每1000000人日的VA粗发病率随着别嘌醇使用时间的增加而下降：1 - 180天，151；181天至2年，105；超过2年，85。在多变量调整分析中，与未使用相比，使用别嘌醇与较低的VA风险比相关，HR为0.82（95%CI，0.76 - 0.90）。与未使用别嘌醇相比，更长的别嘌醇使用时间与更低的多变量调整后VA风险比显著相关：1 - 180天，0.96（95%CI，0.85 - 1.08）；181天至2年，0.76（95%CI，0.68 - 0.85）；超过2年，0.72（95%CI，0.60 - 0.87）。针对心脏疾病、抗心律失常药物和替代定义进行的多项敏感性分析证实了我们的发现，估计值几乎没有/没有衰减。
使用别嘌醇以及使用时间超过6个月与较低的VA风险独立相关。未来的研究需要评估这种潜在益处的病理生理学机制。
