Cardiovascular risks associated with aromatase inhibitors versus tamoxifen in breast cancer: A systematic review and meta-analysis.

Abstract

12018 Background: Aromatase inhibitors (AIs), such as anastrozole, letrozole, and exemestane, are commonly used in the treatment of women with early or advanced-stage breast cancer (BC). However, the potential cardiovascular risks associated with AI treatment, particularly the occurrence of cardiovascular events (CVEs) such as acute myocardial infarction and ischemic stroke, remain a concern. This meta-analysis aims to evaluate the impact of AI and tamoxifen treatment on the risk of CVEs in women with BC. Methods: A comprehensive search was performed across PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) and cohort studies comparing cardiovascular outcomes in patients with BC receiving AIs (anastrozole, letrozole, or exemestane) versus those receiving tamoxifen. Data were analyzed using a random-effects model, and the odds ratios (OR) with 95% confidence intervals (CI) were calculated. P values > 0.10 and I2 values > 25% were considered to indicate significance for heterogeneity. Statistical analysis was performed using R, version 4.4.2. Results: Sixteen studies, involving 188,635 participants, were included in the analysis, of whom 124,473 (65.98%) received AI treatment. A statistically significant difference was observed in heart failure and cardiomyopathy, with the treatment showing an increased risk of these events (OR: 1.48; 95% CI [1.11 to 1.99]; p = 0.0079; I2: 79%). Similarly, myocardial infarction was also significantly more likely to occur in the AI group (OR 1.20; 95% CI [1.01 to 1.42]; p = 0.033; I2: 59%). Thromboembolic events were less frequent in the AI group compared to the Tamoxifen group (OR 0.75; 95% CI [0.56 to 0.99]; p = 0.044; I2: 82%). Arrhythmia was associated with a HR of 1.2306 (95% CI [0.8295 to 1.8255]; p = 0.302; I2: 89%). Cardiovascular death had a HR of 1.09 (95% CI [0.86 to 1.40]; p = 0.451; I2: 55%), and stroke had a HR of 1.0233 (95% CI [0.90 to 1.15]; p = 0.715; I2: 41%). Cardiovascular death in terms of OR was 1.26 (95% CI [0.94 to 1.69]; p = 0.128; I2: 84%), and the risk of cardiovascular events was associated with an OR of 1.38 (95% CI [0.99 to 1.92]; p = 0.054; I2: 64%). Heart failure and cardiomyopathy had a HR of 1.24 (95% CI [0.98 to 1.56]; p = 0.064; I2: 79%), while thromboembolic events had a HR of 1.02 (95% CI [0.88 to 1.17]; p = 0.774; I2: 0%). The HR for myocardial infarction was 1.12 (95% CI [0.93 to 1.36]; p = 0.214; I2: 59%). Hypertension was associated with an OR of 1.07 (95% CI [0.94 to 1.21]; p = 0.2866; I2: 40%), and stroke had an OR of 1.10 (95% CI [0.91 to 1.33]; p = 0.320; I2: 66%). Conclusions: This systematic review and meta-analysis indicate that AI treatment in BC patients is associated with an increased risk of heart failure, cardiomyopathy, and myocardial infarction. Notably, AI treatment demonstrated a protective effect against thromboembolic events.