The effect of ACE-I/ARBs and beta blockers on the development of cardiotoxicity in patients with breast cancer

Abstract

Abstract Introduction Cardiovascular disease has become the leading cause of mortality among breast cancer survivors. Patients with breast cancer who receive treatment with anthracycline and trastuzumab therapies are at risk for the development of non-ischemic cardiomyopathy. The development of heart failure during chemotherapy administration often results in interruption of these life saving therapies. Purpose We aim to investigate whether ACE Inhibitors/angiotensin receptor blockers (ACE-I/ARBs) and beta-blockers can be used as primary prophylaxis to prevent the development of chemotherapy induced cardiomyopathy. Methods This was a retrospective cohort study investigating women who were diagnosed with breast cancer at our medical center from January 2000 to December 2021. The primary endpoint was the development of cardiotoxicity after treatment with chemotherapy. Cardiotoxicity was defined as a decrease of LVEF by 5% or more to less than 55% in the presence of symptoms of heart failure or an asymptomatic decrease in LVEF by 10% or more to less than 55%. Cox-proportional hazard ratios were conducted to determine the impact of prophylactic ACE/ARBs and beta-blockers on the development of cardiotoxicity. Other baseline characteristics were also investigated for their potential impact on the primary endpoint. Results There were 459 patients included in the study of which 70 met criteria for chemotherapy induced cardiomyopathy. Median follow up time of included patients was 12 months and average age was 55 years. Among the included patients, 52% were treated with only trastuzumab, 34% were treated with only anthracycline, and 14% were treated with both therapies. Before chemotherapy was initiated, 15% of patients were taking only ACE-I/ARBs, 7% were taking only beta-blockers, and 5% of patients were taking a combination of ACE-I/ARBS and beta-blockers. There were no significant protective benefits noted for patients who were taking ACE-I/ARBs [HR: 0.49, 95% CI (0.17–1.4)], beta-blockers [HR: 0.50, 95% CI (0.16–1.6)], or both [HR: 1.30, 95% CI (0.44–3.9)]. Notably, there was an increased risk of cardiotoxicity noted for patients who were older [HR: 1.04, 95% CI (1.01–1.1)], smokers within the past 10 years [HR: 2.54, 95% CI (1.41–4.6)], or received a combination of both trastuzumab and anthracycline therapy [HR: 2.52, 95% CI (1.01–6.3)]. Conclusion Prophylactic use of ACE-I/ARBs and beta-blockers separately or in combination was not associated with beneficial reduction in the development of non-ischemic cardiomyopathy in patients receiving anthracycline or trastuzumab therapies. Older age, smoking within the past 10 years, and combination therapy with both anthracycline and trastuzumab were found to be associated with an increased risk. Further studies are needed to investigate the etiology of how smoking may augment the potential cardiotoxic effects in this population. Funding Acknowledgement Type of funding sources: None.