Meta-analysis Evaluating the Use of Statins to attenuate Cardiotoxicity in Cancer Patients receiving Anthracyclines and Trastuzumab-based Chemotherapy

Abstract

Anthracycline and trastuzumab are essential adjuvant therapies for a variety of cancers, particularly breast, and gastric and esophageal cancers. 1 Chotenimitkhun R D'Agostino R Lawrence JA Hamilton CA Jordan JH Vasu S Lash TL Yeboah J Herrington DM Hundley WG Chronic statin administration may attenuate early anthracycline-associated declines in left ventricular ejection function. Can J Cardiol. 2015; 31 (Available from) (Accessed May 10, 2021): 302-307http://pmc/articles/PMC4410009/ Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar Anthracyclines inhibit topoisomerase II which arrests DNA growth, while trastuzumab is a monoclonal antibody directed against the extracellular portion of HER2 receptor. 2 O'Hare M Sharma A Murphy K Mookadam F Lee H Cardio-oncology Part I: Chemotherapy and cardiovascular toxicity. Expert Rev Cardiovasc Ther. 2015; 13 (Available from) (Accessed June 13, 2021): 511-518https://www.tandfonline.com/doi/abs/10.1586/14779072.2015.1032940 Crossref PubMed Scopus (17) Google Scholar Whilst prolonging cancer-related survival, these agents can induce drug-related cardiotoxicity. This causes an increased risk of heart failure (HF). 3 Abdel-Qadir H Bobrowski D Zhou L Austin PC Calvillo-Argüelles O Amir E Lee DS Thavendiranathan P Statin exposure and risk of heart failure after anthracycline-or trastuzumab-based chemotherapy for early breast cancer: A propensity score‒matched cohort study. J Am Heart Assoc. 2021; 10 (Available at:) (Accessed May 10, 2021): 1-12https://www.ahajo Crossref Scopus (13) Google Scholar Cardioprotective agents used to mitigate cardiotoxicity, such as angiotensin antagonists, angiotensin receptor blockers and beta‐blockers, are often poorly tolerated in these patients due to intravascular volume fluctuations, which are further escalated by the hemodynamic side effects of these agents. 4 O'Hare M Murphy K Mookadam F Sharma A Lee H Cardio-oncology Part II: The monitoring, prevention, detection and treatment of chemotherapeutic cardiac toxicity. Expert Rev Cardiovasc Ther. 2015; 13 (Available at:) (Accessed June 13, 2021): 519-527https://www.tandfonline.com/doi/abs/10.1586/14779072.2015.1027686 Crossref PubMed Scopus (9) Google Scholar Statins or HMG-CoA reductase inhibitors may exert a favorable cardio-protective effect during anthracycline and/or trastuzumab treatment owing to its pleiotropic, anti-oxidative and anti-inflammatory effects. However, in the absence of dedicated, appropriately powered randomized trials, evidence of statin used to mitigate cardiac injury only comes from small observational studies. Therefore, we sought to conduct a meta-analysis to examine the association of statin exposure with incidence of cardiac injury in cancer patients who received anthracyclines and/or trastuzumab treatment.