Though potentially life-saving, implantable-cardioverter defibrillator (ICD) shocks can produce a wide range of adverse effects on myocardial function in ICD- and cardiac resynchronization therapy defibrillator (CRT-D)–treated patients, leading to pain, impaired quality of life, and an increased risk of death. Multiple inappropriate shocks have also been shown to lead to the progression of HF.

Beta-blockers have emerged as a potential method to reduce the burden of inappropriate shocks—due to their ability to slow ventricular rate in AF and reduce the risk that sinus tachycardia will trigger ICD shocks. In a recent study published in JACC, Martin H. Ruwald, MD, and colleagues evaluated the effects of carvedilol and metoprolol—the most commonly used beta-blockers in HF patients—in curtailing incidence of inappropriate shocks in patients from the MADIT-CRT study.

A total of 1,790 mildly symptomatic HF patients received either an ICD or CRT-D. Carvedilol was the most commonly prescribed medication (1,077 [61%]), followed by metoprolol (438 [24%]). A total of 120 patients (7%) were not on any beta-blocker due to intolerance, asthma, and other causes.

Inappropriate therapy occurred overall in 253 (14%) patients during a mean follow-up period of 3.4 years. Carvdeilol had a greater impact on risk reduction for the primary endpoint than other beta-blockers—proving the authors’ initial hypothesis correct.

Atrial fibrillation caused inappropriate therapy in 86 patients (5%); and, again, carvedilol was more effective than metoprolol (HR = 0.50; 95% CI 0.32-0.81; p = 0.004). There were, however, no differences found on inappropriate therapy for non-atrial tachyarrhythmias and non-arrhythmic causes of inappropriate therapy for either beta-blocker.

“The major and novel finding of this study was the significant difference on all measured outcomes between carvedilol and metoprolol,” Dr. Ruwald and authors wrote, noting that this reduction remained independently significant throughout the study on inappropriate antitachycardia pacing and shocks. “Preferably any beta-blocker with optimal impact on appropriate and inappropriate therapy is of choice, particularly because beta-blockers are the standard treatment of heart failure in the first place,” they continued. “This, along with previous results, suggests that carvedilol may be the drug of choice in heart failure patients with implanted devices.”

Several factors were proposed to explain the differences in carvedilol’s and metoprolol’s performances, including the differences in their adrenergic receptor selectivity and ancillary properties. Ruwald et al. also pointed out that carvedilol decreases levels of cardiac norepinephrine and suppresses beta-receptors, while metoprolol increase catecholamines and enhances the sensitivity of the heart to beta-receptor stimulation.

“Is there any reason to believe that these differences might make carvedilol more effective at reducing inappropriate shocks?” Merritt H. Raitt, MD, asked in an accompanying editorial. “Since all MADIT-CRT patients had severe left ventricular dysfunction, it may be reasonable to postulate that improved control of heart failure might make atrial fibrillation and other supraventricular tachycardias less likely to occur.... It is also possible that carvedilol’s more potent antiadrenergic activity might reduce the risk that a rapid ventricular response to atrial fibrillation will trigger ICD therapy.”

While the results of the study by Dr. Ruwald and colleagues were “plausible,” Dr. Raitt wrote, he noted some limitations to the analysis, particularly in the dosages: “When the doses of patients taking metoprolol were converted to equivalent doses of carvedilol, the dose was significantly less than that taken by patients on carvedilol. Robust statistical methods were employed to correct for these baseline differences but they are so profound that one has to question whether statistical methods can really fully correct for them or if other unmeasured difference may be driving the results.”

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Raitt MH. J Am Coll Cardiol. 2013 June 12. [Epub ahead of print]
Ruwald MH, Abu-Zeitone A, Jons C, et al. J Am Coll Cardiol. 2013 June 12. [Epub ahead of print]

Keywords: Defibrillators, Follow-Up Studies, Receptors, Adrenergic, Risk Reduction Behavior, Catecholamines, Norepinephrine, Propanolamines, Pain, Cardiac Resynchronization Therapy, Incidence, Carbazoles, Quality of Life, Tachycardia, Sinus, Heart Failure, Ventricular Dysfunction, Left

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