Tianyi Huang1, Mary K Townsend2, Robert L Dood3, Anil K Sood4, Shelley S Tworoger5. 1. Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America. Electronic address: tih541@mail.harvard.edu. 2. Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, FL, United States of America. 3. Department of Obstetrics and Gynecology, The University of Utah School of Medicine, Salt Lake City, UT, United States of America. 4. Department of Gynecologic Oncology, MD Anderson Cancer Center, Houston, TX, United States of America. 5. Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, FL, United States of America; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States of America.
Abstract
OBJECTIVE: Although experimental models suggest that use of beta-blockers, a common antihypertensive agent, may improve survival in ovarian cancer patients, results from clinical studies have been mixed. METHODS: We evaluated the associations of pre-diagnostic (n = 950) and post-diagnostic (n = 743) use of antihypertensive medications with survival among patients with invasive, epithelial ovarian cancer in the Nurses' Health Study (NHS; 1994-2016) and NHSII (2001-2017), with follow-up until 2018 and 2019, respectively. Cox proportional hazards models were used to estimate hazard ratios (HR) for ovarian cancer mortality according to antihypertensive medication use before and after diagnosis, considering multiple drug classes (beta-blockers, calcium-channel blockers, thiazide diuretics, angiotensin-converting enzyme [ACE] inhibitors). RESULTS: After adjusting for age, BMI, smoking status and tumor characteristics, pre-diagnostic use versus non-use of calcium-channel blockers was associated with higher ovarian cancer mortality (HR: 1.49; 95% CI: 1.13, 1.96), which was primarily due to polytherapy involving calcium-channel blockers (HR: 1.61; 95% CI: 1.15, 2.26). Pre-diagnostic use of beta-blockers, thiazide diuretics, or ACE inhibitors was not associated with ovarian cancer mortality. No association was observed for post-diagnostic antihypertensive medication use individually or in combination, except for lower mortality associated with polytherapy involving ACE inhibitors (HR: 0.53; 95% CI: 0.31, 0.91). CONCLUSION: Overall, we did not find clear relationships between antihypertensive medication use and ovarian cancer mortality. However, given the limitation of the data, we cannot determine whether the association may differ by type of beta-blockers. The reasons underlying the observed associations with pre-diagnostic calcium-channel blocker use and post-diagnostic ACE inhibitor use require further investigation.
OBJECTIVE: Although experimental models suggest that use of beta-blockers, a common antihypertensive agent, may improve survival in ovarian cancer patients, results from clinical studies have been mixed. METHODS: We evaluated the associations of pre-diagnostic (n = 950) and post-diagnostic (n = 743) use of antihypertensive medications with survival among patients with invasive, epithelial ovarian cancer in the Nurses' Health Study (NHS; 1994-2016) and NHSII (2001-2017), with follow-up until 2018 and 2019, respectively. Cox proportional hazards models were used to estimate hazard ratios (HR) for ovarian cancer mortality according to antihypertensive medication use before and after diagnosis, considering multiple drug classes (beta-blockers, calcium-channel blockers, thiazide diuretics, angiotensin-converting enzyme [ACE] inhibitors). RESULTS: After adjusting for age, BMI, smoking status and tumor characteristics, pre-diagnostic use versus non-use of calcium-channel blockers was associated with higher ovarian cancer mortality (HR: 1.49; 95% CI: 1.13, 1.96), which was primarily due to polytherapy involving calcium-channel blockers (HR: 1.61; 95% CI: 1.15, 2.26). Pre-diagnostic use of beta-blockers, thiazide diuretics, or ACE inhibitors was not associated with ovarian cancer mortality. No association was observed for post-diagnostic antihypertensive medication use individually or in combination, except for lower mortality associated with polytherapy involving ACE inhibitors (HR: 0.53; 95% CI: 0.31, 0.91). CONCLUSION: Overall, we did not find clear relationships between antihypertensive medication use and ovarian cancer mortality. However, given the limitation of the data, we cannot determine whether the association may differ by type of beta-blockers. The reasons underlying the observed associations with pre-diagnostic calcium-channel blocker use and post-diagnostic ACE inhibitor use require further investigation.
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