High-Sensitivity Cardiac Troponin I-Guided Combination Angiotensin Receptor Blockade and Beta-Blocker Therapy to Prevent Cardiac Toxicity in Cancer Patients Receiving Anthracycline Chemotherapy - Cardiac CARE

Contribution To Literature:

The Cardiac CARE trial failed to show that cardio-protection with beta-blocker/angiotensin receptor blocker prevents left ventricular systolic dysfunction.


The goal of the trial was to evaluate cardio-protection (beta-blocker/angiotensin receptor blocker) compared with standard of care among patients with a high risk of cardiotoxicity after anthracycline chemotherapy.

Study Design

  • Randomized
  • Parallel
  • Blinded
  • Open-label

Patients with a high risk of cardiotoxicity after anthracycline chemotherapy were randomized to cardio-protection (n = 29) vs. standard of care (n = 28) (nonrandomized, n = 118). Cardiotoxicity was defined as elevation in cardiac enzyme (troponin I). Cardio-protection was defined as combined use of carvedilol plus candesartan.

  • Total number of enrollees: 175
  • Duration of follow-up: 6 months
  • Mean patient age: 54 years
  • Percentage female: 79%
  • Percentage with diabetes: 0%

Inclusion criteria:

  • Patients ≥18 years of age with breast cancer or non-Hodgkin’s lymphoma undergoing anthracycline chemotherapy
  • Elevation in troponin I >upper tertile
  • Left ventricular ejection fraction (LVEF) ≥50%

Exclusion criteria:

  • Human epidermal growth factor receptor 2-positive breast cancer
  • Lower-dose anthracycline regimen
  • Ongoing treatment with angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, or beta-blockers
  • Hypotension or hypertension
  • Previous anthracycline chemotherapy

Principal Findings:

The primary outcome, adjusted change in LVEF from baseline to 6 months, was −1.3% in the cardio-protection group vs. −0.9% in the standard of care group (p = 0.82).

Secondary outcomes:

  • Any adverse event: 71.4% with cardio-protection vs. 10.3% with standard of care


Among patients undergoing treatment with anthracycline chemotherapy with signs of cardiotoxicity, cardio-protection with combined beta-blocker/angiotensin receptor blocker failed to prevent left ventricular systolic dysfunction.


Henriksen PA, Hall P, MacPherson IR, et al. Multicenter, Prospective, Randomized Controlled Trial of High-Sensitivity Cardiac Troponin I–Guided Combination Angiotensin Receptor Blockade and Beta-Blocker Therapy to Prevent Anthracycline Cardiotoxicity: The Cardiac CARE Trial. Circulation 2023;Sep 25:[Epub ahead of print].

Clinical Topics: Cardio-Oncology, Heart Failure and Cardiac Biomarkers

Keywords: Cardiotoxicity, Troponin I

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