Hypertension treatment hydrochlorothiazide could increase skin cancer risks

Key takeaways:

• Longer use of hydrochlorothiazide was linked to an increased risk for keratinocyte carcinoma and melanoma.
• Patients on hydrochlorothiazide vs. calcium channel blockers had a 32% higher hazard ratio of melanoma.

Patients treated with hydrochlorothiazide for hypertension may face an increased risk for certain skin cancers with longer duration of use, according to a study.

“Hydrochlorothiazide (HCTZ) is among the most widely used antihypertensive drugs, which is recommended as a first-line treatment for hypertension. However, this thiazide diuretic has photosensitizing properties that may induce an abnormal skin response to ultraviolet light, raising concerns that it may increase the risk of skin cancer,” Laurent Azoulay, PhD, of the Centre for Clinical Epidemiology at Jewish General Hospital in Montreal, and colleagues wrote.

Previous studies have had mixed findings in terms of skin cancer association with HCTZ. This large, multi-site population-based cohort study compared HCTZ use with two comparators — angiotensin-converting enzyme inhibitors (ACEIs) and calcium channel blockers (CCBs) — to determine if an increased risk for these cancers is associated with the drug.

Using administrative health databases from six Canadian provinces, researchers assembled two new-use, active comparator cohorts. Patients treated with HCTZ were compared with those treated with ACEIs in the primary comparison and compared with users of CCBs in the secondary comparison.

Patients were followed for a mean of 5.5 years in the primary comparison, which found no overall association between HCTZ and a risk for keratinocyte carcinoma when compared with ACEIs (incidence rates: 796 vs. 768 per 100,000 person-years; HR = 1.02; 95% CI, 0.98-1.07).

However, when patients cumulatively used HCTZ for 5 to 10 years (HR = 1.09; 95% CI, 1.04-1.14) and more than 10 years (HR = 1.12; 95%; CI: 1.03-1.21), an increased risk for keratinocyte carcinoma was reported.

Higher cumulative doses also increased the risk, with elevated hazard ratios in these groups.

No overall increased risk for melanoma was reported with HCTZ treatment compared with ACEIs and there was no evidence of duration or dose-response relations, according to the study.

When compared with CCBs, an overall risk for keratinocyte carcinoma was also not found, but elevated hazard ratios were recorded with longer duration of treatment and higher cumulative doses.

Melanoma, however, had a 32% increased risk in patients treated with HCTZ, with risk continuing to increase with longer treatment duration and cumulative doses.

“Given the importance of HCTZ in the treatment of hypertension, physicians, patients and decision-makers must weigh benefits and risk compared with other antihypertensive drugs,” the authors wrote.