Prophylactic use of carvedilol to prevent ventricular dysfunction in patients with cancer treated with doxorubicin

Abstract

Objective: Deterioration in ventricular function is often observed in patients treated with anthracyclines for cancer. There is a paucity of evidence on interventions that might provide cardio-protection. We investigated whether prophylactic use of carvedilol can prevent doxorubicin-induced cardiotoxicity and whether any observed effect is dose related.

Methods: A prospective, randomized, double-blind study in patients treated with doxorubicin, comparing placebo (n = 38) with different doses of carvedilol [6.25 mg/day (n = 41), 12.5 mg/day (n = 38) or 25 mg/day (n = 37)]. The primary endpoint was the measured change in left ventricular ejection fraction (LVEF) from baseline to 6 months.

Results: LVEF decreased from 62 ± 5% at baseline to 58 ± 7% at 6-months (p = 0.002) in patients assigned to placebo but no statistically significant changes were observed in any of the 3 carvedilol groups. At 6 months, only one of 116 patients (1%) assigned to carvedilol had an LVEF < 50% compared to four of the 38 assigned to placebo (11%), (p = 0.013). No significant differences were noted between carvedilol and placebo in terms of the development of diastolic dysfunction, clinically overt heart failure or death.

Conclusions: Carvedilol might prevent deterioration in LVEF in cancer patients treated with doxorubicin. This effect may not be dose related within the studied range.

Keywords: Cardiomyopathy; Carvedilol; Doxorubicin; Ejection fraction.

Fig. 1

LVEF at baseline and 6 months among different doses.

Fig. 2

Individual left ventricle ejection fraction at baseline and 6-months.