The use of modern cancer therapies has increased the overall survival rate among patients with cancer. The long-term effects of cancer have been associated with cardiac dysfunction, which includes heart failure and coronary heart disease. One population-based study showed breast cancer survivors were 1.8 times more likely to die of cardiovascular disease (CVD) seven years after diagnosis than the general population. Recent studies have examined whether antihypertensive medications can decrease the incidence of heart failure in patients with cancer. According to an expert panel from the American Society of Clinical Oncology (ASCO), there has been insufficient evidence to suggest that antihypertensive medications prevent cardiac dysfunction. After the ASCO guidelines, research was conducted in randomized controlled trials (RCTs). However, RCTs were not designed to determine CVD events, but examine proxy endpoints of cardiac function. However, observational cohort studies were designed to determine long-term outcomes. The Reding Group, from the Division of Public Health Sciences, analyzed the use of antihypertensive medications and long-term CVD outcomes in women with and without cancer in the Women’s Health Initiative (WHI). The study was published in The Oncologist.
The Women’s Health Initiative (WHI), a large, multi-center study, includes 4 clinical trials and an observational study with several follow-up periods. WHI collected data from postmenopausal women; older women are at a higher risk of CVD and the WHI followed women for a sufficient time to evaluate long-term CVD outcomes in relation to antihypertensive medications. The Reding Group only included women who used at least one antihypertensive medication at baseline or during the follow-up period that occurred before cardiac dysfunction; there were a total of 56,997 participants. The outcome of the study included: coronary heart disease (CHD), myocardial infarction (MI), coronary death, and heart failure (HF). The exposure variable was antihypertensive medication; the medications include angiotensin-converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), beta blockers (BBs), and diuretics.
Multivariable-adjusted Cox regression models with interaction terms to account for the influence of cancer incidence were used to estimate hazard ratios. The primary analyses compared use of ACEi/ARB (n=9,837), diuretic (n=10,441), or CCB (n=5,785) with BB (n=8,617). In cancer survivors, women who used ACEi/ARB had a 2.24 increased risk of total cardiac events in comparison to women who used BB (95% CI:1.18-4.24). In the non-cancer cohort, no difference was detected in the risk of cardiac events among antihypertensive medications (p=0.63). With CHD as the only cardiac event, there was a significant difference in the risk of CHD associated with antihypertensive medications that was predominantly driven by the elevated risk in cancer survivors who used ACEi/ARB compared to women free of cancer (p=0.04).
The findings suggest that BB use is more favorable in reducing cardiac events than ACEi/ARB use for cancer survivors. However, the findings were different for cancer-free women. It’s important to analyze the exposures and outcomes in other observational studies, which could provide evidence that antihypertensive medications have different effects in cancer survivors and the cancer free population.
Dr. Reding summarized the article, “Prior studies have predominantly investigated this question in adults without cancer, whereas our study was able to inform on this relationship in cancer survivors due to the large number of cancer survivors in the Women's Health Initiative study population. Since its inception, the Women's Health Initiative has focused on risk factors for and assessment of cardiovascular disease and cancer, from which our publication benefitted. The study was able to investigate this research question due to the extensive data collected over multiple decades in the WHI studies which includes rigorous ascertainment of medication data and diagnosis data. “
This research was supported by the National Heart, Lung, and Blood Institute, the National Institutes of Health, and the U.S. Department of Health and Human Services.
Fred Hutch/UW Cancer Consortium members Drs. Kerryn Reding, Eric Chow, Chu Chen, and Wendy Barrington contributed to this study.
Reding, K. W., Aragaki, A. K., Cheng, R. K., Barac, A., Wassertheil-Smoller, S., Chubak, J., Chlebowski, R. T. 2020. Cardiovascular Outcomes in Relation to Antihypertensive Medication Use in Women with and Without Cancer: Results from the Women’s Health Initiative. The Oncologist. http://doi.org/10.1634/theoncologist.2019-0977