In a large cohort of approximately 4 million individuals, the risk for both melanoma and nonmelanoma skin cancer could not be differentiated between individuals exposed to hydrochlorothiazide vs angiotensin-converting enzyme (ACE) inhibitors, according to study results published in Hypertension.
Previous research into skin cancer risk among individuals using hydrochlorothiazide has shown conflicting results. Researchers sought to assess the risk for melanoma and nonmelanoma among patients exposed to hydrochlorothiazide (exposure of interest) vs ACE inhibitors (active comparator), as well as potential effect modifiers such as race and ethnicity.
The researchers used the IBM MarketScan Research Databases (which contain de-identified patient-level claims data on in-hospital and outpatient resources in the US) to conduct 3 cohort studies in individuals at least 18 years of age. There were more than 3.5 million individuals in the Commercial Claims and Encounters cohort (2010-2018; approximately 51% women; hypertension in approximately 68% of patients), 415,330 individuals in the health risk assessment (HRA) subcohort (approximately 50% women; hypertension in approximately 67% of patients), and 509,767 individuals in the Medicaid cohort (2011-2017; 65% women; hypertension in approximately 34% of patients). A first-filled prescription for hydrochlorothiazide or ACE inhibitor with at least 12 months continuous enrollment with pharmacy/medical coverage before cohort entry was the determinant for cohort assignments. Individuals who had used either hydrochlorothiazide or ACE inhibitors or a combination product within 12 months of cohort entry, and those with HIV, prior skin cancer, or organ transplant were excluded.
Aside from a higher percentage of Black patients within the hydrochlorothiazide group (43.3% vs 28.1% of ACE inhibitor users), baseline characteristics were similar. Data on race/ethnicity were only available in the Medicaid database.
The researchers used multivariate proportional hazards regression to compare risks associated with hydrochlorothiazide vs ACE inhibitor exposure. Assessment for nonmelanoma skin cancer related to hydrochlorothiazide vs ACE inhibitors showed no differentiation in terms of hazard ratio (HR) between the commercial cohort (HR, 0.96; 95% CI, 0.91-1.00), the HRA cohort (HR, 1.01; 95% CI, 0.77-1.32), and the Medicaid cohort (HR, 1.33; 95% CI, 0.77-2.29).
There was no HR differentiation between the commercial cohort (HR, 1.07; 95% CI, 0.95-1.20), the HRA cohort (HR, 0.85; 95% CI, 0.43-1.67), or the Medicaid cohort (HR, 0.93; 95% CI, 0.51-1.67) with relation to melanoma development related to hydrochlorothiazide vs ACE inhibitor use.
These results for both nonmelanoma and melanoma skin cancer failed to establish a clear difference in skin cancer risk between use of hydrochlorothiazide vs ACE inhibitors.
Study limitations include missing data on the proportion of White populations naturally at greater risk for skin cancer, and unaccounted-for concomitant use of other prescribed antihypertensives that are photosensitizing agents (such as amiloride).
“Hydrochlorothiazide, one of the most commonly prescribed antihypertensives, has photosensitivity properties that potentially increase skin cancer risk,” the researchers wrote. They concluded, “Hydrochlorothiazide could increase the risk of skin cancer, although we did not observe a clear difference in skin cancer risk among hydrochlorothiazide and ACE (angiotensin-converting enzyme) inhibitor users, even when controlling for race/ethnicity.”
References:
Birck MG, Moura CS, Machado MAA, et al. Skin cancer and hydrochlorothiazide: novel population-based analyses considering personal risk factors including race/ethnicity. Hypertension. Published online July 25, 2023. doi:10.1161/HYPERTENSIONAHA.123.21274
