Introduction: Patients with implantable cardioverter defibrillators (ICD) are often treated with amiodarone. We sought to determine if the efficacy of ranolazine, a late-Na current blocker therapy, differs according to amiodarone use.
Methods: RAID was a double-blind, placebo- controlled clinical trial of high-risk ICD patients with nonischemic or ischemic cardiomyopathy that randomized patients to ranolazine 1,000 mg bid versus placebo. Concomitant amiodarone antiarrhythmic therapy was permitted.
Results: Overall, there were 1,012 patients enrolled (mean age: 64±10 years; 18% women), among which 102 received amiodarone (52 in the placebo arm) and 908 did not receive amiodarone (450 in placebo arm). Those treated with amiodarone at baseline were more often male (92 vs 80%, p=0.004), had lower heart rate (66±12 vs 72±12 bpm, p<.001), a lower estimated glomerular filtration (63±19 vs 77±25 mL/min/1.73 m2, p<.001), were more likely to be implanted for secondary prevention ICD (43 vs 33%, p=0.037), and if implanted for primary prevention were more likely to have had prior ventricular arrhythmia (49 vs 36%, p=0.008). Within the placebo arm, amiodarone was not associated with higher or lower unadjusted rates of VT/VF (amiodarone 23% vs 29% no amiodarone, p=0.35) or the primary endpoint composite of VT/VF requiring ATP/shock or death (amiodarone 31% vs 40% no amiodarone, p=0.18). There was evidence of a potential interaction between amiodarone status and ranolazine (p=0.148) for the primary endpoint. Among those without amiodarone therapy, the primary endpoint was reduced with ranolazine (adjusted HR 0.79, 95%CI: 0.63-0.99; p=0.045). In patients taking amiodarone there was no evidence of reduction in the primary endpoint with ranolazine (adjusted HR 1.36, 95%CI: 0.68-2.74; p=0.386).
Conclusions: Ranolazine led to a reduction in the occurrence of VT/VF requiring ATP or shock or death in patients who were not taking amiodarone. These benefits are not evident in patients receiving both amiodarone and ranolazine.