Description:
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<jats:title>Objectives:</jats:title>
<jats:p>The use of hydrochlorothiazide has recently been linked to skin cancer in observational studies. This may be explained by its photosensitizing properties, but photosensitivity has also been reported for other antihypertensive drugs. We conducted a systematic review and meta-analysis to compare skin cancer risk among antihypertensive drug classes and between individual blood pressure lowering drugs.</jats:p>
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<jats:title>Methods:</jats:title>
<jats:p>We searched Medline, Embase, Cochrane and the Web of Science to 9th of February 2022 and included studies that investigated the association between antihypertensive medication exposure and non-melanoma skin cancer (NMSC) or cutaneous malignant melanoma (CMM). We combined the extracted adjusted odds ratios (OR) using a random effects model. We performed sensitivity analyses comparing study type, population and studies with and without correction for important covariates.</jats:p>
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<jats:title>Results:</jats:title>
<jats:p>We included 43 studies. Diuretics (n = 17,729,595), in particular hydrochlorothiazide (n = 17,710,679), and calcium channel blockers (CCB, n = 8,413,919) were examined more frequently than beta-blockers (n = 94,872) or renin-angiotensin system inhibitors (n = 2,019,786). Exposure to diuretics (OR 1.30, 95% CI [1.12–1.52]) and CCB (OR 1.06, 95% CI [1.04–1.09]) was associated with an increased risk for NMSC. No antihypertensive drug class was associated with an increased risk for CMM. Within every drug class, at least 1 individual drug was associated with an increased risk for NMSC: nifedipine, hydrochlorothiazide, sotalol, verapamil, enalapril and bendroflumethiazide. Increased NMSC risk was only observed in case-control studies and in studies that did not correct for important covariates. No increased NMSC risk was observed in cohort studies and studies that did correct for the covariates sun exposure, skin phototype or smoking. (Figure) Only 2 out of 43 studies provided information about antihypertensive co-medication. Eggers test revealed a significant publication bias for the subgroup of diuretics and hydrochlorothiazide concerning NMSC (both p < 0.001).</jats:p>
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<jats:title>Conclusion:</jats:title>
<jats:p>Of all antihypertensive drugs, diuretics and calcium channel blockers may be associated with an increased risk of NMSC, but causal inferences remain difficult to make because of aforementioned substantial limitations in available data and evidence of publication bias.</jats:p>
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