Patients who took the diuretics hydrochlorothiazide or indapamide long term were found to have an increased risk of developing specific types of skin cancer compared with patients who took calcium channel blockers, according to the results of an observational cohort study recently published in the British Journal of Dermatology.
Using a primary care database for the United Kingdom, study researchers identified patients who were aged 18 to 85 and who began taking thiazides, thiazide-like diuretics, or calcium channel blockers between January 1, 1998, and December 31, 2017.
Patients were followed to determine whether they developed basal cell carcinoma, squamous cell carcinoma, or cutaneous malignant melanoma.
The cohort was weighted by propensity score to control for baseline covariates, allocating 271,154 patients to the group deemed new users of thiazides or thiazide-like diuretics and 275,263 to new users of calcium channel blockers. The new users of thiazides or thiazide-like diuretics were prescribed bendroflumethiazide (87.6%), indapamide (5.8%), or hydrochlorothiazide (3.6%).
The incidence rate for squamous cell carcinoma was higher among patients prescribed hydrochlorothiazide long-term compared with patients prescribed calcium channel blockers (0.8% vs 0.3%), translating to a 1.95 increased risk (95% CI, 1.87-2.02). The absolute excess risk for patients prescribed hydrochlorothiazide long term was 87.4 diagnoses of squamous cell carcinoma per 100,000 person-years of long-term hydrochlorothiazide use.
The incidence rate for cutaneous malignant melanoma was higher among patients who took indapamide long term compared with patients who took calcium channel blockers, translating to a 1.43 increased risk (95% CI, 1.35-1.50).
Although short-term use of bendroflumethiazide was associated with a 1.36 increased risk of cutaneous malignant melanoma (95% CI, 1.23-1.48), long-term use was not associated with an increased risk of basal cell carcinoma, squamous cell carcinoma, or cutaneous malignant melanoma.
The study researchers concluded that bendroflumethiazide may be a “safer alternative” to hydrochlorothiazide and indapamide, especially for patients at increased risk for skin cancer but noted that future studies are needed to rule out a causal association between bendroflumethiazide and cutaneous malignant melanoma.
Schneider R, Reinau D, Stoffel S, Jick SS, Meier CR, Spoendlin J. Risk of skin cancer in new users of thiazides and thiazide-like diuretics: a cohort study using an active comparator group. Br J Dermatol. Published online February 20, 2021. doi:10.1111/bjd.19880