Introduction: Statins may reduce risk for ventricular tachyarrhythmia (VTA) in patients with implantable cardioverter defibrillator (ICD). Ranolazine was shown to increase plasma concentrations of statin. Objective: To evaluate the effect of statin on recurrent VTA, and to explore the interaction with both Ranolizine and cardiomyopathy (CMP) origin. Methods: The Andersen-Gill extension of the Cox proportional hazards regression was used to assess the association between statin treatment and the risk for recurrent VTA among 1012 ICD patients enrolled in the Ranolazine Implantable Cardioverter-Defibrillator Trial (RAID). Interaction-term analysis with ranolazine and ischemic status were performed. Number of events was limited to a maximum of 10 VTA events per patient to avoid any patients having an undue influence on model estimates. Results: A total of 740 (73%) RAID patients were treated with statins. Multivariable analysis showed that statin use was associated with an overall 30% reduction in the risk for recurrent VTA (HR=0.70; p<0.001)(Figure). Interaction analysis showed that the benefit of statin use was seen only among patients with non-ischemic CMP (HR=0.53 [95%CI 0.41-0.69]; p<0.001), whereas there was no evidence of benefit among patients with ischemic CMP for recurrent VTA (HR=1.03 [95%CI 0.70-1.54] p=0.70), with an interaction p-value of <0.01 for the differential effect of statin use on recurrent VTA by CMP origin. The effect of statin was relatively consistent and did not differ significantly between the ranolazine and placebo arms (Figure). Statin use was not associated with increased adverse events, and ranolazine discontinuation was higher among those who were not treated with statins vs. those who received statin therapy (53% vs 42%, respectively; p<0.01). Conclusion: Our findings suggest that treatment with statin (regardless if with or without ranolazine) is highly effective in reducing VTA burden in non-ischemic ICD recipients.