Association of hydrochlorothiazide exposure with all-cause mortality among US cancer survivors: A prospective cohort study

Hydrochlorothiazide (HCTZ) is commonly prescribed to cancer patients. However, there is a paucity of research examining the effects of HCTZ exposure on the mortality risk of cancer survivors. We constructed a prospective cohort using data from the National Health and Nutrition Examination Survey from 2003 to 2018 to investigate the associations between HCTZ exposure and the risk of all-cause mortality among cancer survivors. The participants were categorized into 2 groups based on their self-reported use of HCTZ. Multivariate-adjusted Cox proportional hazards models were used to assess the survival outcomes between groups. Multivariate-adjusted logistic regression models were conducted to investigate the association between HCTZ exposure and the risk of cardiovascular disease and cerebrovascular disease. The final cohort comprised 4202 cancer survivors, with a mean age (standard deviation) of 66.01 ± 14.35 years. Of these, 53.2% were females, and 68.4% were non-Hispanic White individuals. The medication stratification identified 3517 non-HCTZ-exposed individuals and 685 HCTZ-exposed individuals. During a mean follow-up of 6.93 years (maximum 17 years), 1337 deaths were recorded. Compared with non-HCTZ-exposed individuals, HCTZ-exposed individuals presented reduced risk of all-cause mortality (hazard ratio = 0.80, 95% confidence interval [CI] = 0.67–0.95; P  = .003). Cross-sectional studies have indicated that exposure to HCTZ is associated with a lower risk of angina pectoris (odds ratio = 0.81, 95% CI = 0.72–0.93; P  < .001) and heart attack (odds ratio = 0.89, 95% CI = 0.84–0.95; P  = .001). HCTZ exposure is likely correlated with a lower risk of all-cause mortality in cancer survivors. However, HCTZ use among participants was assessed only once via self-report, lacking detailed information on dosage, duration of use, indication, cancer stage, and treatment regimens, precluding definitive conclusions regarding a protective effect of HCTZ. Further research is warranted to confirm these findings.