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

Abstract

Summary 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.

Use of hydrochlorothiazide and risk of skin cancer in a large nested case‐control study in Spain

“…Results for KC in BIFAP were generally similar to results from a Danish study, 8 in which high use of HCTZ increased the risk of BCC by 1.3 times (1.1 times in BIFAP) and the risk of SCC by four (1.7 times in BIFAP). Recently, studies from the United Kingdom (UK) also using a primary care database, 11–13 showed similar results. In these studies HCTZ was related to KC too, especially to SCC.…”

“…However, most findings were not directly comparable mainly due to differences in the study methods used and study‐specific limitations. Recently, several studies have found an increased risk of skin and lip cancer related to high cumulative doses of hydrochlorothiazide (HCTZ) in populations from Denmark, 7–9 Iceland, 10 United Kindom 11–13 and Australia, 14 but not in a population from Taiwan 15 …”

Increased cutaneous squamous cell carcinoma risk with hydrochlorothiazide use: is there a safe alternative?

“…confirm the strongly increased risk of cutaneous squamous cell carcinoma (cSCC) in a cohort study using a UK primary care database. 7 Although, weak associations with melanoma and basal cell carcinoma (BCC) have been observed in some studies, these were not observed in the cohort study of Schneider et al . 7 …”

“… 7 Although, weak associations with melanoma and basal cell carcinoma (BCC) have been observed in some studies, these were not observed in the cohort study of Schneider et al . 7 …”

“…Therefore, external validation of their results is of vital importance. While the association with hydrochlorothiazide and cSCC is now externally validated in multiple studies, 7 , 8 Schneider et al . confirmed that bendroflumethiazide is an example of a safe alternative for prescribing physicians, in terms of choice of thiazide for patients at increased risk of nonmelanoma skin cancer.…”