Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Department of Dermatology, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan.
Br J Dermatol. 2015 Aug;173(2):498-509. doi: 10.1111/bjd.13884. Epub 2015 Jun 21.
Although healthcare products regulatory agencies have issued warnings on risk of ulceration associated with the use of nicorandil, a population-based study has not been carried out.
To determine the relationship between use of nicorandil and skin ulceration.
We carried out a population-based study using a cohort of 1 million people assembled from Taiwan's national health insurance database. The association between nicorandil use and skin ulcers was estimated by a Cox proportional hazards regression model adjusting for a nicorandil-specific propensity score (PS) comprising of 86 potential predictors (c-statistic = 0·91).
The prospective cohort was longitudinally followed from January 2005 to December 2009, during which 1268 new users of nicorandil and 771 136 nonusers were identified. A higher frequency of skin ulcers (29 of 1268; 2·3%) was observed for users of nicorandil compared with nonusers (3231 of 771 136; 0·4%). Compared with nonusers, the crude hazard ratio (HR) associating nicorandil use with skin ulcers was 5·52 [95% confidence interval (CI) 3·82-7·95] and the PS-adjusted HR was 1·85 (95% CI 1·27-2·69). A risk period analysis showed that the risk of skin ulceration among users of nicorandil was greatest in the first year. Subgroup analysis found that the interaction term reached statistical significance (P < 0·05) for age and diabetes.
Use of nicorandil was found to be associated with an increased risk for skin ulceration, especially in the first year after incident exposure. We suggest that regulatory agencies re-evaluate the risk for skin ulceration associated with use of nicorandil.
尽管医疗产品监管机构已就尼可地尔相关溃疡风险发出警告，但尚未开展基于人群的研究。
确定尼可地尔的使用与皮肤溃疡之间的关系。
我们开展了一项基于人群的研究，使用来自台湾全民健康保险数据库的 100 万人队列。使用包含 86 个潜在预测因子的尼可地尔专用倾向评分（C 统计量=0.91）的 Cox 比例风险回归模型估计尼可地尔使用与皮肤溃疡之间的关联。
前瞻性队列从 2005 年 1 月至 2009 年 12 月进行了纵向随访，在此期间，确定了 1268 例尼可地尔新使用者和 771 136 例非使用者。与非使用者相比，尼可地尔使用者的皮肤溃疡发生率更高（1268 例中有 29 例[2.3%]）（771 136 例中有 3231 例[0.4%]）。与非使用者相比，尼可地尔使用与皮肤溃疡相关的粗风险比（HR）为 5.52（95%置信区间[CI]为 3.82-7.95），经倾向评分调整后的 HR 为 1.85（95%CI 为 1.27-2.69）。风险期分析显示，尼可地尔使用者皮肤溃疡的风险在第一年最高。亚组分析发现，年龄和糖尿病的交互项达到统计学意义（P<0.05）。
尼可地尔的使用与皮肤溃疡风险增加相关，尤其是在首次发生接触后的第一年。我们建议监管机构重新评估尼可地尔相关皮肤溃疡风险。
