During the first year after activation of an implantable cardioverter defibrillator, a combination of amiodarone plus a β-blocker significantly reduced the risk of shock, compared with β-blocker alone or sotalol alone.
Because ICD shocks are painful and have been linked to reduced physical function and mental well-being, efforts should be made to reduce such shocks, wrote Dr. Stuart J. Connolly and associates. However, because amiodarone is associated with an increased risk of pulmonary and thyroid adverse events, “therapeutic decisions should be individualized, taking into account possible improvements in quality of life and the small, but increased, risk of drug-related adverse effects,” wrote Dr. Connolly of McMaster University, Hamilton, Ontario, and his colleagues (JAMA 2006;295:165–71).
In the Optimal Pharmacological Therapy in Cardioverter Defibrillator Patients (OPTIC) trial, the researchers randomized 412 patients with a newly implanted St. Jude Medical dual-chamber ICD for secondary prevention of serious malignant ventricular arrhythmias to either a β-blocker (138), amiodarone plus a β-blocker (140), or sotalol alone (134). Most of the patients (80%) were male; the mean age was 64 and 80% had a history of myocardial infarction.
OPTIC's primary end point was the first occurrence of any shock delivered by the ICD. Compared with a β-blocker alone, amiodarone plus β-blocker significantly reduced the risk of shock (hazard ratio 0.27). Sotalol showed a nonsignificant trend toward reduced risk (hazard ratio 0.61), compared with β-blocker alone.
During the 12-month study, there were 41 shocks in the β-blocker alone group, 26 in the sotalol group, and 12 in the amiodarone plus β-blocker group, translating to event rates of 39%, 24%, and 10%.
Amiodarone plus β-blocker significantly cut the rate of both appropriate and inappropriate shocks, with hazard ratios of 0.30 and 0.27, respectively, compared with β-blocker alone. Reductions in appropriate and inappropriate shocks with sotalol did not reach statistical significance (hazard ratios 0.65 and 0.61, respectively).
The mortality rate was low (3%/year) and did not differ significantly between groups. However, adverse events, especially pulmonary and thyroid events, were significantly higher in the amiodarone group, in which there were seven pulmonary adverse events, six cases of hypothyroidism, and two cases of hyperthyroidism. In the sotalol group, there were four pulmonary adverse events, and one case of hypothyroidism. There were no pulmonary or thyroid adverse events in the β-blocker only group.
The sotalol group had the most patients who discontinued therapy (23%). The discontinuation rate was 18% in the amiodarone group and 5% in the β-blocker group. However, the investigators noted, about 78% of patients were already on β-blockers at baseline, so this could have reduced the dropout rate in that group.
In the early days of ICDs, continuing antiarrhythmic drug therapy was usually discontinued because it “seemed redundant, akin to 'a belt plus suspenders,'” Dr. Richard L. Page wrote in an accompanying editorial. But antiarrhythmic therapy can reduce or eliminate shocks by suppressing ventricular arrhythmias or by slowing ventricular tachycardia to the extent that it can be corrected with programmed pacing.
He agreed, however, that drug therapy after ICD implantation should be individualized. In addition to adverse events, antiarrhythmic drugs can interfere with the device function by increasing, rather than decreasing, the defibrillation threshold (JAMA 2006;295:211–3).
“At present, all patients with an ICD who can tolerate such therapy should receive a β-blocker,” wrote Dr. Page of the University of Washington, Seattle. “The addition of amiodarone or substitution with sotalol cannot be advocated for all patients and should be considered on an individual basis.”