Association between antihypertensive medications and risk of skin cancer in people older than 65 years: a population-based study

• Published in: Canadian Medical Association journal (CMAJ) Vol. 193; no. 15; pp. E508 - E516
• Main Authors: Drucker, Aaron M., Hollestein, Loes, Na, Yingbo, Weinstock, Martin A., Li, Wen-Qing, Abdel-Qadir, Husam, Chan, An-Wen
• Format: Journal Article
• Language: English
• Published: Canada Elsevier Inc 12.04.2021; Joule Inc; CMA Impact, Inc
• Subjects: Adrenergic beta-Antagonists - therapeutic use; Age; Aged; Aged patients; Angiotensin Receptor Antagonists - therapeutic use; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Antihypertensive Agents - adverse effects; Antihypertensive Agents - therapeutic use; Antihypertensive drugs; Antihypertensives; Calcium Channel Blockers - therapeutic use; Carcinoma - epidemiology; Cohort Studies; Complications and side effects; Diuretics; Drug dosages; Drug therapy; Enzymes; Female; Health risks; Humans; Hypertension - drug therapy; Internal Medicine; Male; Melanoma; Melanoma - epidemiology; Older people; Ontario - epidemiology; Population-based studies; Risk Factors; Skin cancer; Skin Neoplasms - epidemiology; Sodium Chloride Symporter Inhibitors - adverse effects; Sodium Chloride Symporter Inhibitors - therapeutic use; Statistical analysis; Statistics; Sunlight - adverse effects; Thiazides; Ontario; Canada; United States > US
• DOI: 10.1503/cmaj.201971
• ISSN: 0820-3946; 1488-2329

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.