%0 Journal Article
%T Geographical differences in hydrochlorothiazide associated risk of skin cancer balanced against disability related to hypertensive heart disease.
%A Almskou A
%A Buus NH
%A Steffensen SGC
%J Am J Hypertens
%V 0
%N 0
%D 2024 Aug 8
%M 39115345
%F 3.08
%R 10.1093/ajh/hpae101
%X <B>BACKGROUND: </B>Hypertension affects 25-30% of the world population. Hydrochlorothiazide (HCTZ) is among the most used and cheapest medications but was in 2018 labeled with a warning stating increased risk of non-melanoma skin cancer (NMSC). This study describes geographical differences in the association between HCTZ and NMSC in a perspective of hypertensive heart disease (HHD).<BR><B>METHODS: </B>We conducted a systematic literature search (PubMed, Embase, Clinicaltrial.gov, and Clinicaltrial.eu) using PICO/PECO acronyms including case-control, cohort, and randomized controlled trials. We constructed a rate ratio of disability-adjusted life years (DALY) for HHD/NMSC in global burden of disease (GBD) regions.<BR><B>RESULTS: </B>No increased risk of NMSC with use of HCTZ was found in Taiwan, India, and Brazil. A small (hazard ratio (HR)/odds ratio (OR) ≤ 1.5) but significantly increased risk was seen in Canada, USA, and Korea. An increased risk (1.5 < HR/OR ≤ 2.5) in Iceland, Spain, and Japan and a highly increased risk (HR/OR > 2.5 in UK, Denmark, Netherlands, and Australia. HHD is associated with a more than 10-fold DALY rate compared with NMSC in 13 of 21 GBD regions corresponding 77.2% of the global population. In none of these 13 regions were there an increased risk of HCTZ-associated NMSC.<BR><B>CONCLUSIONS: </B>Despite limited information from many countries, our data point to large geographical differences in the association between HCTZ and NMSC. In all GBD regions, except Australasia, HHD constitutes a more than 5-fold DALY rate compared to NMSC. This disproportionate risk should be considered before avoiding HCTZ as part of the antihypertensive treatment.