Association of hydrochlorothiazide treatment compared with alternative diuretics with overall and skin cancer risk: a propensity-matched cohort study

Abstract

Introduction:Hydrochlorothiazide (HCT) has been suggested to induce photosensitivity, thereby increasing the incidence of skin cancers. After a pharmacovigilance alert, HCT was frequently withdrawn or substituted by other diuretics. The aim of this study was to compare the association of exposure to HCT with cancer risk versus alternative diuretics.Methods:A retrospective cohort study was conducted based on data from the AOK PLUS, a large German statutory health insurance fund. Patients with HCT treatment were propensity score matching to patients using non-HCT diuretics. Incidence of cancer of any kind and, specifically, skin cancer was assessed in both groups. Time-to-incident cancer diagnosis was evaluated and compared between the groups.Results:A total of 199 708 patients were included in the final analysis (n = 76 855 in the HCT group; n = 122 853 in the non-HCT-diuretics group). After propensity score matching, 122 554 patients remained in the sample (n = 61 277 for both groups, of which >96% had hypertension, mean age 73 years, 61% female). HCT treatment was associated with a lower incidence of cancer of any kind compared with non-HCT diuretics (incidence rate ratio per 100 patient years 0.84 95% confidence interval: 0.82–0.87). HCT treatment was associated with a small albeit significantly higher incidence rate ratio of skin cancer (1.15 95% confidence interval: 1.06–1.24) with significant variances over time. Although numerically higher, the difference accounts to only 0.05 more skin cancer diagnoses in 100 patient-years.Conclusion:HCT treatment compared with alternative diuretics was associated with a lower all-cancer risk and a numerically small increased skin cancer risk in a large German population. Risk–benefit evaluation should be executed in patients with increased skin cancer risk and treatment with HCT. Furthermore, advice for skin protection is warranted in all patients taking thiazide or thiazide-like diuretics.

2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension

“…However, the increased risk was seen only in women, and no biological rationale was offered for this finding [687]. Finally, a large propensity-matched cohort study in Germany found that hydrochlorothiazide was associated with not only a small increase of skin cancer risk but also with an overall lower risk for any cancer compared with other diuretics [688]. Further well designed observational studies are needed to provide a more solid evidence on the association between hydrochlorothiazide and skin cancer risk.…”

Phototoxic Reactions Inducted by Hydrochlorothiazide and Furosemide in Normal Skin Cells—In Vitro Studies on Melanocytes and Fibroblasts

“…Although both commonly known and used drugs such as HCT and FUR are initially subjected to phototoxicity test, many new reports, systematic reviews, and cohort studies of phototoxic reactions have been reported as an adverse effects of pharmacotherapy with these drugs [14,[27][28][29]. Moreover, a lot of recent pharmacoepidemiological data have appeared to link a dose-dependent, cumulative association between long-term HCT treatment and increased risk of skin cancer [24,[27][28][29].…”

“…Although both commonly known and used drugs such as HCT and FUR are initially subjected to phototoxicity test, many new reports, systematic reviews, and cohort studies of phototoxic reactions have been reported as an adverse effects of pharmacotherapy with these drugs [14,[27][28][29]. Moreover, a lot of recent pharmacoepidemiological data have appeared to link a dose-dependent, cumulative association between long-term HCT treatment and increased risk of skin cancer [24,[27][28][29]. The meta-analyses of the relationship between pharmacotherapy with thiazide diuretics and the risk of skin cancer demonstrated an increased risk of developing non-melanoma skin cancers-squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), for which the OR value was 1.86 and 1.19, respectively, and melanoma cancer (OR 1.14) [30].…”

Diuretika bei arterieller Hypertonie

“…Propensity Score Matching) erfolgte. Nach dem Abschluss der Auswertung ergab sich auch hier ein leicht erhöhtes Hautkrebsrisiko von 0,05 Hautkrebsdiagnosen mehr auf 100 Patientenjahre für die HCT-Gruppe, demgegenüber steht jedoch die signifikant niedrigere Inzidenzrate für alle Krebsarten in der HCT-Gruppe [18]. Dies deckt sich auch mit einer Metaanalyse aus dem Jahr 2021, in der kein Zusammenhang zwischen einem Antihypertensivum im Allgemeinen und einem erhöhten Krebsrisiko identifiziert werden konnte [19].…”