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Anthracycline, a component of effective chemotherapy for certain malignancies, can cause cardiotoxicity, manifested as left-ventricular systolic dysfunction (LVSD) and heart failure. Two new trials address the role of ACE inhibitors and beta-blockers, effective therapies for established LVSD, in preventing chemotherapy-induced cardiotoxicity. Neither trial had a double-blind design.
In a single-center study from Italy, 473 consecutive patients without structural heart disease had their troponin I (TnI) levels checked five times within 72 hours after undergoing high-dose chemotherapy. The 114 patients with at least one TnI reading above 0.07 ng/mL (mean LV ejection fraction, 63%) were randomized to receive or not receive the ACE inhibitor enalapril. Enalapril was started 1 month after the last chemotherapy cycle, initially at 2.5 mg daily and titrated up to 20 mg daily. At 1 year, incidence of the primary endpoint — a >10% decline in resting LVEF to <50% — was significantly higher in the control group than in the enalapril group (43% vs. 0%). Enalapril recipients were less likely than controls to have persistently elevated TnI levels. Within the control group, persistent TnI elevation was associated with greater declines in LVEF.
In a single-center randomized trial from Turkey, 25 patients (mean LVEF, 70%) with plans to undergo anthracycline chemotherapy received either the beta-blocker carvedilol (12.5 mg daily) or placebo. By a mean follow-up of 5.2 months, mean LVEF had declined significantly more with placebo than with carvedilol (by 17% vs. 1%), and significantly more placebo recipients than carvedilol recipients had reached LVEFs <50% (5 vs. 1). Placebo recipients also experienced significant increases in LV systolic and diastolic diameters.
Cardinale D et al. Prevention of high-dose chemotherapy–induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibitors. Circulation 2006 Dec 5; 114:2474-81.
Kalay N et al. Protective effects of carvedilol against anthracycline-induced cardiomyopathy. J Am Coll Cardiol 2006 Dec 5; 48:2258-62.
Granger CB. Prediction and prevention of chemotherapy-induced cardiomyopathy: Can it be done? Circulation 2006 Dec 5; 114:2432-3.
Comment
These two studies provide encouraging evidence for mitigating the adverse cardiac effects of anthracycline chemotherapy; the data from the study of troponin-guided ACE-inhibitor therapy are more robust. An editorialist reminds us that open-label designs tend to inflate the benefits of therapy but concludes that, given the relatively low risk from ACE inhibitors, using them to prevent chemotherapy-induced cardiotoxicity is reasonable. We don’t yet know whether beta-blockers are equally effective, whether combination therapy would provide incremental benefit over ACE-inhibitor therapy alone, or whether either drug class would be effective with other cardiotoxic chemotherapeutic agents (e.g., Gleevec; see Journal Watch Cardiology Nov 1 2006).