Aromatase inhibitors use and risk for cardiovascular disease in breast cancer patients: A population-based cohort study

Abstract

Background: Prior studies regarding use of Aromatase inhibitors (AIs) and risk for cardiovascular disease (CVD) have shown conflicting results. This retrospective cohort study aimed to investigate whether AIs use affects risk for CVD events in postmenopausal breast cancer survivors. Methods: Using a retrospective cohort study design, four CVD outcomes; heart failure or cardiomyopathy, arrhythmia, acute ischemic heart disease and ischemic stroke or Transient Ischemic Attack were compared with uni-and multivariate Cox regression analyses according to exposure to endocrine therapy (use of AI, tamoxifen or AI/tamoxifen sequentially) or no endocrine therapy. Results: In total 15815 postmenopausal women, surgically treated to early breast cancer during 2006 e2012, were included. No significantly increased risk for CVD events was observed in patients with AI use in the whole cohort. However, two subgroup analyses showed increased risk for CVD events in the AI/tamoxifen sequential group; heart failure in patients older than 75 years (Hazard Ratio (HR) 2.44; 95% Confidence Interval (CI): 1.32e4.54) and arrhythmia in patients without prior CVD (HR 1.45; 95% CI: 1.01 e2.10). An increased risk for arrhythmia and acute ischemic heart disease in patients with at least four years of AI treatment compared with no or short-time exposure was observed (HR 2.12; 95% CI: 1.40 e3.25 for arrhythmia; HR 2.03; 95% CI: 1.15e3.58 for ischemic heart disease). Conclusion:Our results indicate an increased risk for ischemic heart disease and arrhythmia in patients treated for more than four years with AIs. This should be considered in the risk-benefit assessment concerning endocrine therapy.

Adjuvant aromatase inhibitor therapy and early markers for cardiovascular disease in breast cancer survivors

“…The cohort study by Ligibel et al (n = 44,463) suggests the former: when BC patients using AI were compared with BC patients not receiving ET, there was no association between AI use and risk of MI or stroke with a median follow-up of 2.5 years [33]. Sund et al also observed no association of AI use and MI or HF when compared to non-users in their cohort study including 15,815 women with a median follow-up of 3.9 years [34].…”

Aromatase Inhibitors and Risk of Metabolic and Cardiovascular Adverse Effects in Breast Cancer Patients—A Systematic Review and Meta-Analysis

“…The occurrence of cardiovascular events may also depend on the duration of therapy and the type of AI. Results from a population-based cohort study conducted by Sund et al indicated an increased risk for arrhythmia and acute ischemic heart disease in patients treated for more than four years with AIs [ 36 ]. In turn, a network meta-analysis performed by Zhao et al showed the total and severe cardiovascular events’ risk ranking for letrozole, exemestane and anastrozole in descending order [ 37 ].…”

Breast Cancer Epidemiology and Contemporary Breast Cancer Care: A Review of the Literature and Clinical Applications

“…AIs are also associated with an increased risk of cardiovascular events when compared with tamoxifen 131. This could partly be secondary to the cardioprotective effect of tamoxifen, as it acts as an estrogen agonist in the vasculature 132. Due to these potential risks, breast cancer follow-up should include a cardiovascular review of systems and a close partnership with the patient’s primary care provider for a periodic lipid screen and appropriate risk factor modifications.…”