Cardioprotective Effect of Statins in Patients With HER2-Positive Breast Cancer Receiving Trastuzumab Therapy

Can J Cardiol. 2019 Feb;35(2):153-159. doi: 10.1016/j.cjca.2018.11.028. Epub 2018 Dec 4.

Abstract

Background: Statins can reduce the risk of anthracycline-induced cardiotoxicity. Whether such cardioprotective effects can be seen in trastuzumab-treated patients has not been explored.

Methods: Consecutive women with HER2+ breast cancer who received trastuzumab with or without anthracyclines were identified retrospectively. Patients receiving statins before and during cancer treatment were matched with 2 patients of the same age (± 2 years) and anthracycline exposure status but without statin treatment. The primary outcome was final left ventricular ejection fraction (LVEF). Analysis of covariance (ANCOVA) was used to assess the relationship between statin exposure and the final LVEF. A logistic regression model was constructed to assess the relationship between statin exposure and cardiotoxicity (secondary outcome).

Results: Included were 129 patients (62 ± 9 years). Forty-three received statins during cancer treatment. The median trastuzumab exposure time was 11.8 (interquartile range [IQR] 11 to 12) months. Seventy-two (56%) patients received anthracyclines. Compared with controls, patients treated with statins were more likely to have diabetes (37.2% vs 4.7%, P < 0.001), hypertension (58.1% vs 22.1%, P < 0.001), and coronary artery disease (11.6% vs 2.3%, P = 0.04). Within a median cardiac follow-up duration of 11 (IQR 9 to 18) months, the adjusted final LVEF was lower in the control group (61.2% vs 64.6%, P = 0.034). A significant change in LVEF was observed in the control group (median -6%, IQR -10% to -1% P < 0.001) but not in the statin group (median 0%, IQR -5% to +3%, P = 0.27). Upon adjusted analysis, statin treatment was independently associated with a lower risk of cardiotoxicity (odds ratio [OR] 0.32, 95% confidence interval [CI], 0.10-0.99, P = 0.049).

Conclusions: In women with HER2+ breast cancer receiving trastuzumab-based therapy with or without anthracyclines, concomitant use of statins was associated with a lower risk of cardiotoxicity.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Immunological / therapeutic use
  • Breast Neoplasms / complications
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Case-Control Studies
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Heart Diseases / chemically induced
  • Heart Diseases / physiopathology
  • Heart Diseases / prevention & control*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Middle Aged
  • Receptor, ErbB-2 / metabolism*
  • Retrospective Studies
  • Stroke Volume / drug effects
  • Trastuzumab / adverse effects
  • Trastuzumab / therapeutic use*
  • Ventricular Function, Left / drug effects

Substances

  • Antineoplastic Agents, Immunological
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab

Grants and funding