Candesartan and carvedilol for primary prevention of subclinical cardiotoxicity in breast cancer patients without a cardiovascular risk treated with doxorubicin

Cancer Med. 2021 Jun;10(12):3964-3973. doi: 10.1002/cam4.3956. Epub 2021 May 16.

Abstract

Background: There is no proven primary preventive strategy for doxorubicin-induced subclinical cardiotoxicity (DISC), especially among patients without a cardiovascular (CV) risk. We investigated the primary preventive effect on DISC of the concomitant use of angiotensin receptor blockers (ARBs) or beta-blockers (BBs), especially among breast cancer patients without a CV risk.

Methods: A total of 385 patients who were scheduled for doxorubicin chemotherapy were screened. Among them, 195 patients of the study populations were included and were randomly divided into two groups [candesartan 4 mg q.d. vs. carvedilol 3.125 mg q.d.] and patients who were unwilling to take one of the medications were evaluated as controls. The primary outcomes were the incidence of early DISC (DISC developing within 6 months after chemotherapy), and late DISC (DISC developing only at least 12 months after chemotherapy).

Result: Compared with the control group (8 out of 43 patients (18.6%)), only the candesartan group (4 out of 82 patients (4.9%)) showed a significantly lower incidence of early DISC (p = 0.022). Compared with the control group, the candesartan group demonstrated a significantly reduced decrease in left ventricular ejection fraction (LVEF) throughout the study period [-1.0% vs. -3.00 (p < 0.001) at the first follow-up, -1.10% vs. -3.40(p = 0.009) at the second follow-up].

Conclusions: Among breast cancer patients without a CV risk treated with doxorubicin-containing chemotherapy, subclinical cardiotoxicity is prevalent and concomitant administration of low-dose candesartan might be effective to prevent an early decrease in LVEF. Further large-scale, randomized controlled trials will be needed to confirm our findings.

Keywords: adrenergic beta-antagonists; angiotensin receptor antagonists; anthracyclines; breast cancer; cardiomyopathies; prevention.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use
  • Angiotensin Receptor Antagonists / therapeutic use
  • Antibiotics, Antineoplastic / adverse effects*
  • Antibiotics, Antineoplastic / therapeutic use
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / therapeutic use*
  • Benzimidazoles / administration & dosage
  • Benzimidazoles / therapeutic use*
  • Biphenyl Compounds / administration & dosage
  • Biphenyl Compounds / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Cardiotoxicity / epidemiology
  • Cardiotoxicity / prevention & control*
  • Carvedilol / administration & dosage
  • Carvedilol / therapeutic use*
  • Cyclophosphamide / therapeutic use
  • Docetaxel / therapeutic use
  • Doxorubicin / adverse effects*
  • Doxorubicin / therapeutic use
  • Female
  • Humans
  • Incidence
  • Middle Aged
  • Risk Assessment
  • Stroke Volume / drug effects
  • Tetrazoles / administration & dosage
  • Tetrazoles / therapeutic use*
  • Ventricular Function, Left / drug effects

Substances

  • Adrenergic beta-Antagonists
  • Angiotensin Receptor Antagonists
  • Antibiotics, Antineoplastic
  • Antihypertensive Agents
  • Benzimidazoles
  • Biphenyl Compounds
  • Tetrazoles
  • Carvedilol
  • Docetaxel
  • Doxorubicin
  • Cyclophosphamide
  • candesartan