Association of hydralazine use with risk of hematologic neoplasms in patients with hypertension: A nationwide population-based cohort study in Taiwan.

Abstract

Onco-hypertension recognizes well-controlled blood pressure as a favorable prognostic factor for survival in patients with hypertension and solid tumors, including hematologic neoplasms. However, it remains unknown whether continuous use of hydralazine-an antihypertensive agent (AHA) with notable anti-neoplastic activity-is associated with a lower risk of hematologic neoplasms compared to other AHAs. Utilizing Taiwan's National Health Insurance Research Database, we conducted a 16-year follow-up study (2000-2015) involving 375,107 patients with hypertension treated with an AHA for ≥180 days. The patients with hypertension were divided into two groups based on hydralazine prescription duration: an exposure group (hydralazine ≥180 days; n = 59,786) and a reference group (hydralazine <180 days; n = 239,144) after 1:4 matching for sex, age, and index date with the exposure group. Both groups were well-matched, with a mean age of approximately 60.8 years and 52.19% male. We assess the association between hydralazine use and the risk of hematologic neoplasms using Kaplan-Meier analysis and multivariable Cox proportional hazards regression, with models adjusted for concomitant medications possessing potential anti-neoplastic properties. The 16-year cumulative incidence of hematologic neoplasms was lower in the exposure group (105.58 per 100,000 person-years) than in the reference group (160.33). Accounting for death as competing risk, the exposure group exhibited an adjusted subdistribution hazard ratio (adjusted sHR) of 0.789 (95% confidence interval [0.667,0.913]; P < .001) for hematologic neoplasms compared to the reference group. Subgroup analyses demonstrated that the association with a lower risk was strongest in the longest prescription duration category. For example, for patients with prescription durations of ≥668 days, the adjusted sHR was 0.448 (95% CI [0.366,0.555]; P < .001) for other malignant neoplasms of lymphoid and histiocytic tissue, 0.552 (95% CI [0.453,0.683]; P < .001) for multiple myeloma and immunoproliferative neoplasms, and 0.555 (95% CI [0.457,0.689]; P < .001) for myeloid leukemia. The main limitation was the potential for residual confounding due to the unavailability of lifestyle and laboratory data in the administrative database. In this study, we observed that long-term hydralazine use in patients with hypertension was associated with a lower, duration-dependent risk of hematologic neoplasms. These findings warrant prospective studies to confirm this association and its potential clinical implications.