Ivabradine in Cancer Treatment-Related Left Ventricular Dysfunction

Chemotherapy. 2018;63(6):315-320. doi: 10.1159/000495576. Epub 2019 Mar 6.

Abstract

Background: Patients developing cancer treatment-related left ventricular dysfunction (CTrLVD) require a prompt therapy. Hypotension, dizziness, and fatigue often limit the use of angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), and β-blockers (BB) in cancer patients who may already be afflicted by these symptoms. Ivabradine is a heart rate-lowering drug that does not cause hypotension and may be used in heart failure with reduced left ventricular ejection fraction (LVEF).

Objective: The aim of this paper was to investigate the role of ivabradine to treat CTrLVD.

Methods: A retrospective analysis in a cohort of 30 patients with CTrLVD (LVEF < 50%) receiving ivabradine on top of the maximal tolerated dose of ACEi/ARB and BB was performed. We evaluated cardiovascular treatment, oncologic treatment, LVEF, functional class (New York Heart Association [NYHA]), and fatigue during the study period.

Results: Ivabradine was initially started at the dose of 2.5 mg/b.i.d. in most patients and then carefully titrated. Hypotension (70%) and fatigue (77%) were the main causes limiting the treatment with ACEi/ARB and BB. After a mean follow-up of 6.5 months, LVEF increased from 45.1% (SD = 6.4) to 53.2% (SD = 3.9; p < 0.001). When patients were analyzed according to the type of cancer therapy, no difference in LVEF changes across the groups was found. NYHA class ameliorated in 11 patients, while fatigue improved in 8 patients. No serious cardiovascular side effects were reported.

Conclusions: The ability to improve symptoms and LVEF in unfit cancer patients makes ivabradine a reasonable pharmacological tool for treating CTrLVD.

Keywords: Adverse drug reaction; Cancer; Cardio-oncology; Cardiotoxicity; Heart failure; Hypotension; Ivabradine.

MeSH terms

  • Adrenergic beta-Antagonists / adverse effects
  • Adrenergic beta-Antagonists / therapeutic use
  • Adult
  • Aged
  • Angiotensin Receptor Antagonists / adverse effects
  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Anthracyclines / adverse effects
  • Anthracyclines / therapeutic use
  • Cardiovascular Agents / adverse effects*
  • Cardiovascular Agents / therapeutic use
  • Dose-Response Relationship, Drug
  • Fatigue / etiology
  • Female
  • Heart Rate
  • Humans
  • Ivabradine / adverse effects*
  • Ivabradine / therapeutic use
  • Male
  • Middle Aged
  • Neoplasms / drug therapy
  • Retrospective Studies
  • Trastuzumab / adverse effects
  • Trastuzumab / therapeutic use
  • Ventricular Dysfunction, Left / etiology*

Substances

  • Adrenergic beta-Antagonists
  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Anthracyclines
  • Cardiovascular Agents
  • Ivabradine
  • Trastuzumab