Risk of cardiovascular disease in breast cancer patients receiving aromatase inhibitors vs. tamoxifen: A systematic review and meta-analysis

J Clin Pharm Ther. 2022 May;47(5):575-587. doi: 10.1111/jcpt.13598. Epub 2022 Jan 4.

Abstract

What is known and objective: Breast cancer is one of the leading causes of morbidity and mortality in women worldwide. In order to reduce the risks of its recurrence, endocrine therapies, such as tamoxifen and aromatase inhibitors are commonly administered. Despite having a similar efficacy in preventing breast cancer recurrence, these drugs differ in terms of instigating cardiovascular morbidities. Recent randomized controlled trials and cohort studies provide inconclusive evidence of the cardiovascular risks associated with the administration of these endocrine therapies. This present review and meta-analysis evaluates the comparative cardiovascular adverse event outcomes in breast cancer patients receiving tamoxifen and aromatase inhibitors. To evaluate the comparative cardiovascular adverse outcomes, such as venous thromboembolism, heart failure, angina, myocardial infarction and stroke in patients with breast cancer receiving tamoxifen and aromatase inhibitors.

Methods: A systematic search of the academic literature was performed according to the PRISMA guidelines across five databases, including Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE. A random-effect meta-analysis was conducted to compare the cardiovascular adverse events (i.e. venous thromboembolism, heart failure, angina, myocardial infarction, stroke) in breast cancer patients treated with tamoxifen and aromatase inhibitors.

Results and discussion: From 993 studies, 20 eligible studies were identified, with 174,142 female breast cancer patients (mean age: 67.4 ± 3.8 years). A meta-analysis revealed insignificantly (p > 0.05) higher risks of venous thromboembolism (Odds ratio, 95% CI: 1.70, 0.91-3.18) in patients treated with tamoxifen as compared to aromatase inhibitors. We also observed insignificantly higher risks of stroke (0.93, 0.45-1.91), angina (0.77, 0.12-4.59), myocardial infarction (0.74, 0.30-1.79), and heart failure (0.81, 0.22-2.91) in patients receiving aromatase inhibitors as compared to tamoxifen.

What is new and conclusions: The study provides evidence regarding the comparative cardiovascular adverse outcomes between breast cancer patients consuming tamoxifen and aromatase inhibitors. The study reports an insignificant increase in the events of stroke, angina, myocardial infarction, and heart failure in breast cancer patients treated with aromatase inhibitors as compared to tamoxifen. The study also reports that tamoxifen treatment is associated with an insignificant increase in the events of venous thromboembolism as compared to treatment with aromatase inhibitors.

Keywords: aromatase inhibitors; breast cancer; cardiovascular disease; endocrine therapy; tamoxifen.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Aged
  • Antineoplastic Agents, Hormonal / adverse effects
  • Aromatase Inhibitors / adverse effects
  • Breast Neoplasms* / chemically induced
  • Breast Neoplasms* / drug therapy
  • Cardiovascular Diseases* / chemically induced
  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / prevention & control
  • Female
  • Heart Failure* / drug therapy
  • Humans
  • Middle Aged
  • Myocardial Infarction* / chemically induced
  • Myocardial Infarction* / drug therapy
  • Myocardial Infarction* / epidemiology
  • Neoplasm Recurrence, Local / drug therapy
  • Stroke* / drug therapy
  • Tamoxifen / adverse effects
  • Venous Thromboembolism* / chemically induced
  • Venous Thromboembolism* / drug therapy

Substances

  • Antineoplastic Agents, Hormonal
  • Aromatase Inhibitors
  • Tamoxifen