Risk of skin cancer in new users of thiazides and thiazide-like diuretics: a cohort study using an active comparator group

BACKGROUND Case-control studies report a dose-dependent increased risk of skin cancer in users of hydrochlorothiazide (HCTZ) vs. nonusers. The degree to which other thiazides and thiazide-like diuretics (TZs) are associated with skin cancer is less certain. OBJECTIVES To assess the risk of skin cancer in new users of different TZs compared with new users of calcium channel blockers (CCBs). METHODS We conducted a cohort study using a UK primary-care database (1998-2017), including 271 154 new TZ users [87·6% bendroflumethiazide (BFT), 5·8% indapamide and 3·6% HCTZ] and 275 263 CCB users. The outcomes were basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and cutaneous malignant melanoma (CMM). We estimated incidence rates (IRs) and IR ratios (IRRs) in short-term (< 20 prescriptions) and long-term (≥ 20 prescriptions) users of TZs and CCBs using negative binomial regression, and calculated rate differences (RDs) for selected results. We used fine stratification on the propensity score (PS) to control for 23 baseline covariates. RESULTS Long-term use of HCTZ increased absolute and relative risks of SCC [PS-weighted IRR 1·95; 95% confidence interval (CI) 1·87-2·02; RD per 100 000 person-years 87.4], but not of BCC or CMM. Long-term use of indapamide was associated with an increased incidence of CMM (IRR 1·43; 95% CI 1·35-1·50). BFT was not meaningfully associated with the risk of any type of skin cancer. CONCLUSIONS Our results corroborate the previously reported increased risk of SCC (but not of BCC or CMM) for long-term use of HCTZ. BFT may be a safer alternative for patients at increased risk of skin cancer.