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Temporal Risk of Non-Melanoma Skin Cancer with Lisinopril and Hydrochlorothiazide as Monotherapy and in Combination: A Retrospective Cohort Study Using the TriNetX Database
Conference poster   Peer reviewed

Temporal Risk of Non-Melanoma Skin Cancer with Lisinopril and Hydrochlorothiazide as Monotherapy and in Combination: A Retrospective Cohort Study Using the TriNetX Database

Taylor Merkle, Celter Odango and Erum Ilyas
Journal of the American Academy of Dermatology, v 95(1), AB429
Jul 2026
DOI: https://doi.org/10.1016/j.jaad.2026.04.1705

Abstract

Thiazide diuretics, namely hydrochlorothiazide (HCTZ), are recognized for their increased risk of nonmelanoma skin cancers (NMSC), however associations with frequent dual combination therapy with angiotensin-converting-enzyme-inhibitors (ACEIs) for superior hypertension (HTN) treatment control has yet to be established. [1,2] A retrospective cohort study using the TriNetX U.S. Collaborative Network was conducted with 4 adult (age >18) cohorts with essential hypertension (HTN, ICD10: I10) (1) HTN without antihypertensive treatment, (2) HTN with Lisinopril (LIS), (3) HTN with HCTZ, or (4) HTN with both LIS + HCTZ. Demographic variables were propensity score matched 1:1 between cohorts excluding patients on other antihypertensives, smoking or organ transplant histories, and prior instances of NMSC. Outcomes assessed were basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) at 5 and 10 years. Significant (p<0.0001) increased risk ratios (RR) were associated at 5 and 10 years respectively with LIS alone for BCC (RR=2.294, 2.216) and cSCC (RR=2.234, 1.925) as well as in combination therapy LIS + HCTZ for BCC (RR=2.332, 2.114) and cSCC (1.885, 2.013). Z-scores between cohorts identified HCTZ alone to carry a significantly greater risk of cSCC at 5 years [RR=3.01 (2.15, 4.213), p<0.0001] when compared to combination LIS+HCTZ. Our study demonstrates that LIS and HCTZ either taken in combination or as monotherapy for HTN increases the risk of NMSC development.

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