Long-term hydrochlorothiazide use ups risk of skin cancer

Using hydrochlorothiazide (HCTZ) for longer durations and in higher cumulative doses increases the risks for keratinocyte carcinoma and melanoma, reveals a study.

A team of investigators conducted a multisite population-based cohort study to determine whether HCTZ was a risk factor for skin cancer as compared to angiotensin-converting enzyme inhibitors (ACEIs) and calcium channel blockers (CCBs).

Six Canadian databases were used to assemble two new-user, active comparator cohorts. The investigators calculated the site-specific hazard ratios (HRs) with 95 percent confidence intervals (CIs) using standardized morbidity ratio weighted Cox proportional hazard models and pooled the data using random-effects meta-analysis.

HCTZ did not result in an overall increased risk of keratinocyte carcinoma when compared with ACEIs and CCBs. However, such risk increased with longer durations of use (≥10 years; HR, 1.12, 95 percent CI, 1.03‒1.21) and higher cumulative doses (≥100,000 mg; HR, 1.49, 95 percent CI, 1.27‒1.76).

For melanoma, no association was observed with ACEIs. However, melanoma risk increased by 32 percent with CCBs (crude incidence rates, 64.2 vs 58.4 per 100,000 person-years; HR, 1.32, 95 percent CI, 1.19‒1.46; estimated number needed to harm at 5-year follow-up: 1,627 patients). This risk further increased with longer durations of use and cumulative doses.

“Increased risks of keratinocyte carcinoma and melanoma were observed with longer durations of use and higher cumulative doses of HCTZ,” the investigators concluded.

Of note, the study was limited by residual confounding due to its observational design.