Is hydrochlorothiazide associated with an increased risk of skin cancer?

Is hydrochlorothiazide associated with an increased risk of skin cancer?

The association between hydrochlorothiazide (HCTZ) and skin cancer remains controversial. A team of investigators from the Canadian Network for Observational Drug Effect Studies (CNODES) led by Dr. Laurent Azoulay and including Dr. Greg Carney of the TI’s Pharmacoepidemiology Working Group carried out a multi-site population-based cohort study to determine whether hydrochlorothiazide (HCTZ) associated with an increased risk of skin cancer compared with angiotensin-converting enzyme inhibitors (ACEIs) and calcium channel blockers (CCBs).

The pre-proof findings are now published in the Journal of the American Academy of Dermatology and available here:

Two new-user, active comparator cohorts were gathered using six Canadian databases. Site-specific hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using standardized morbidity ratio weighted Cox proportional hazard models and pooled using random-effects meta-analysis.

The study found HCTZ was not associated with an overall increased risk of keratinocyte carcinoma compared with ACEIs or CCBs, although increased risks were seen in certain subgroups, including very long duration (≥10 years) and higher cumulative exposure (≥100,000 mg). For melanoma, there was no association with ACEIs, but a 32% increased risk with CCBs (NNH at 5 years = 1,627).

The investigators conclude that increased risks of keratinocyte carcinoma and melanoma were observed with longer durations of use and higher cumulative doses of HCTZ and that given the importance of hydrochlorothiazide in the treatment of hypertension, physicians, patients, and decision-makers must weigh its benefits and risk compared with other antihypertensive drugs.


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