Comparative study on individual aromatase inhibitors on cardiovascular safety profile: a network meta-analysis

Abstract

The third-generation aromatase inhibitors (AIs: anastrozole, letrozole, and exemestane) have now become standard adjuvant endocrine treatment for postmenopausal estrogen receptor-positive breast cancer complementing chemotherapy and surgery. Because of the absence of direct head-to-head comparisons of these AIs, an indirect comparison is needed for individual treatment choice. In this network systemic assessment, the cardiovascular (CV) side effects in using anastrozole, letrozole, and exemestane based on original studies on AIs vs placebo or tamoxifen were compared. We integrated all available direct and indirect evidences. The odds ratio (OR) of severe CV events for indirect comparisons between exemestane and anastrozole was 1.41 (95% confidence interval [CI] =0.49–2.78), letrozole and anastrozole was 1.80 (95% CI =0.40–3.92), and letrozole and exemestane was 1.46 (95% CI =0.34–3.4). OR of subgroup risk for AIs and tamoxifen were all >1 except for thrombolism risk subgroup. The results showed that the total and severe CV risk ranking is letrozole, exemestane, and anastrozole in descending order. None of the AIs showed advantages in CV events than tamoxifen except for thromboembolism event incidence.

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

“…ET endocrine therapy, tam tamoxifen, AI aromatase inhibitor, IQR interquartile range, BC breast cancer, BRCA breast cancer gene a p value for between-group differences, calculated with Kruskal-Wallis test or chi squared tests (excluding the unknown category) b Based on medical file and patient questionnaires c Defined as a systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg, the use of antihypertensive drugs or the medical record d Defined as any diagnosis from category I00-I99, except I10-I15, according to the Internatinal Classification of Diseases, 10th revision (ICD10) e Defined as any diagnosis from category J00-J99 according to the ICD10 f Defined as any diagnosis from category E00-E90 according to the ICD10; includes 14 1). Almost all patients who had received ET had estrogen receptor positive and/or progesterone receptor positive BC (99.1%).…”

“…Whether or not this reflects a true detrimental effect of AIs on cardiovascular disease (CVD) risk or a cardioprotective effect of tamoxifen (mainly attributed to the favorable effect on lipid profile [8]) is a matter of controversy. Several systematic reviews and meta-analyses have addressed the issue, with varying outcomes [9][10][11][12][13][14][15][16]. Given the oncological relevance of AIs, it is important to gain more insight into the cardiovascular safety of AIs and identify potential mechanisms for AI-induced CVD.…”

Comparative study on individual aromatase inhibitors on cardiovascular safety profile: misleading analysis and doubtful methodology

“…Zhao et al have presented the result of the relative cardiovascular safety profile in using anastrozole, letrozole, and exemestane to treat the postmenopausal estrogen receptor-positive breast cancer, in which fatal or nonfatal myocardial infarction is the outcome measure and ten randomized controlled trials are used as the data sources. 1 We congratulate and applaud their important work, but there are some issues of concern.…”