Divisions of Dermatology (Drucker, Chan) and Cardiology (Abdel-Qadir), Department of Medicine, University of Toronto; Department of Medicine and Women's College Research Institute (Drucker, Abdel-Qadir, Chan), Women's College Hospital, Toronto, Ont.; Department of Dermatology (Drucker, Weinstock, Li), Brown University, Providence, RI; Erasmus MC Cancer Institute (Hollestein), Rotterdam, The Netherlands; Department of Research (Hollestein), Netherlands Comprehensive Cancer Center (IKNL), Utrecht, The Netherlands; ICES Central (Drucker, Abdel-Qadir) and ICES University of Toronto (Na, Chan), Toronto, Ont.; Department of Cancer Epidemiology (Li), Peking University Cancer Hospital & Institute, China.
Divisions of Dermatology (Drucker, Chan) and Cardiology (Abdel-Qadir), Department of Medicine, University of Toronto; Department of Medicine and Women's College Research Institute (Drucker, Abdel-Qadir, Chan), Women's College Hospital, Toronto, Ont.; Department of Dermatology (Drucker, Weinstock, Li), Brown University, Providence, RI; Erasmus MC Cancer Institute (Hollestein), Rotterdam, The Netherlands; Department of Research (Hollestein), Netherlands Comprehensive Cancer Center (IKNL), Utrecht, The Netherlands; ICES Central (Drucker, Abdel-Qadir) and ICES University of Toronto (Na, Chan), Toronto, Ont.; Department of Cancer Epidemiology (Li), Peking University Cancer Hospital & Institute, China
CMAJ. 2021 Apr 12;193(15):E508-E516. doi: 10.1503/cmaj.201971.
The risk of skin cancer associated with antihypertensive medication use is unclear, although thiazides have been implicated in regulatory safety warnings. We aimed to assess whether use of thiazides and other antihypertensives is associated with increased rates of keratinocyte carcinoma and melanoma.
We conducted a population-based inception cohort study using linked administrative health data from Ontario, 1998-2017. We matched adults aged ≥ 66 years with a first prescription for an antihypertensive medication (thiazides, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, β-blockers) by age and sex to 2 unexposed adults who were prescribed a non-antihypertensive medication within 30 days of the index date. We evaluated each antihypertensive class in a separate cohort study. Our primary exposure was the cumulative dose within each class, standardized according to the World Health Organization's Defined Daily Dose. Outcomes were time to first keratinocyte carcinoma, advanced keratinocyte carcinoma and melanoma.
The inception cohorts included a total of 302 634 adults prescribed an antihypertensive medication and 605 268 unexposed adults. Increasing thiazide exposure was associated with an increased rate of incident keratinocyte carcinoma (adjusted hazard ratios [HRs] per 1 Defined Annual Dose unit 1.08, 95% confidence interval [CI] 1.03-1.14), advanced keratinocyte carcinoma (adjusted HR 1.07, 95% CI 0.93-1.23) and melanoma (adjusted HR 1.34, 95% CI 1.01-1.78). We found no consistent evidence of association between other antihypertensive classes and keratinocyte carcinoma or melanoma.
Higher cumulative exposure to thiazides was associated with increased rates of incident skin cancer in people aged 66 years and older. Consideration of other antihypertensive treatments in patients at high risk of skin cancer may be warranted.
尽管噻嗪类利尿剂已被纳入监管安全警告中，但与降压药物使用相关的皮肤癌风险尚不清楚。我们旨在评估噻嗪类利尿剂和其他降压药物的使用是否与角质细胞癌和黑色素瘤发生率的增加有关。
我们使用来自安大略省的 1998 年至 2017 年的行政健康数据进行了一项基于人群的发病队列研究。我们通过年龄和性别将年龄≥66 岁且首次开处方使用降压药物（噻嗪类、血管紧张素转换酶抑制剂、血管紧张素 II 受体阻滞剂、钙通道阻滞剂、β受体阻滞剂）的成年人与在指数日期的 30 天内开处方使用非降压药物的 2 名未暴露成年人相匹配。我们在单独的队列研究中评估了每个降压药物类别。我们的主要暴露是根据世界卫生组织规定日剂量标准化的每个类别中的累积剂量。结局是首次角质细胞癌、晚期角质细胞癌和黑色素瘤的发生时间。
发病队列共纳入 302634 名开处方使用降压药物的成年人和 605268 名未暴露成年人。噻嗪类药物暴露量的增加与角质细胞癌（每 1 个定义年剂量单位调整后的危害比 [HR] 1.08，95%置信区间 [CI] 1.03-1.14）、晚期角质细胞癌（调整后的 HR 1.07，95% CI 0.93-1.23）和黑色素瘤（调整后的 HR 1.34，95% CI 1.01-1.78）的发生率增加相关。我们没有发现其他降压药物类别与角质细胞癌或黑色素瘤之间存在一致关联的证据。
噻嗪类药物累积暴露量较高与 66 岁及以上人群中皮肤癌发病率的增加有关。对于皮肤癌风险较高的患者，可能需要考虑其他降压治疗。
