Reduction in ventricular tachyarrhythmias with statins in the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II.

OBJECTIVES: We evaluated whether statins have anti-arrhythmic effects by exploring the association of statin use with appropriate implantable cardioverter-defibrillator (ICD) therapy for ventricular tachycardia/ventricular fibrillation (VT/VF) in the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II. BACKGROUND: A few studies have suggested that lipid-lowering drugs may have anti-arrhythmic effects in patients with coronary artery disease. METHODS: Patients receiving an ICD (n = 654; U.S. centers only) in the MADIT-II study were categorized by the percentage of days each patient received statins during follow-up (90% to 100%, n = 386; 11% to 89%, n = 116; and 0% to 10%, n = 152). The Kaplan-Meier method with significance testing by the log-rank statistic and time-dependent proportional hazards regression analysis were used to evaluate the effect of statin use on the probability of ICD therapy for the combined end point VT/VF or cardiac death and for the end point VT/VF. RESULTS: The cumulative rate of ICD therapy for VT/VF or cardiac death, whichever occurred first, was significantly reduced in those with > or =90% statin usage compared to those with lower statin usage (p = 0.01). The time-dependent statin:no statin therapy hazard ratio was 0.65 (p < 0.01) for the end point of VT/VF or cardiac death and 0.72 (p = 0.046) for VT/VF after adjusting for relevant covariates. CONCLUSIONS: Statin use in patients with an ICD was associated with a reduction in the risk of cardiac death or VT/VF, whichever occurred first, and was associated with a reduction in VT/VF episodes. These findings suggest that statins have anti-arrhythmic properties.

Temporal aspects of improved survival with the implanted defibrillator (MADIT-II).

The present study retrospectively explored the reasons for delay in the onset of survival benefit from the implanted cardioverter defibrillator (ICD) in the Second Multicenter Automatic Defibrillator Implantation Trial. The cumulative probability of cause-specific death over time was estimated by the Kaplan-Meier method and by proportional hazards regression analysis. Early cardiac death survival curves were similar by treatment assignment in the 0- to 12-month period (p = 0.76). Late cardiac death survival curves by treatment assignment in the >12- to 52-month follow-up period were divergent with a lower probability of late cardiac death in the ICD arm compared with conventional therapy group (p <0.001). The time-specific hazard ratios of ICD to conventional therapy for cardiac death in the early and late periods were significantly different from each other (nominal p = 0.004). There was a significant decrease in sudden cardiac death with ICD therapy in the early (p = 0.012) and late (p <0.001) groups. In the early period, the rate of nonsudden cardiac death was significantly higher in the ICD group than in the conventional therapy group (p = 0.003). Rates of late nonsudden cardiac death were similar in the 2 treatment arms (p = 0.11).