Treatment crossovers did not affect randomized treatment comparisons in the Mode Selection Trial (MOST).

OBJECTIVES: We evaluated the impact of treatment crossovers on study results in the Mode Selection Trial (MOST). BACKGROUND: The MOST study, a 2,010-patient, 6-year trial comparing dual-chamber pacing (DDDR) and ventricular pacing (VVIR) in sinus node dysfunction, demonstrated no difference in death or stroke and modest reductions in heart failure hospitalization (HFH) and atrial fibrillation (AF) with DDDR pacing. However, a moderate proportion of VVIR-randomized patients were temporarily or permanently crossed over to DDDR pacing. METHODS: Intent-to-treat (ITT) analyses compared treatment arms by randomized pacing mode. On-treatment analyses used time-dependent covariates to account for all crossovers. All analyses used Cox proportional hazards models and included covariates prespecified in the study design: age, gender, Charlson index, and prior stroke, heart failure, myocardial infarction, supraventricular tachyarrhythmia, and ventricular tachycardia or fibrillation. RESULTS: Of 996 VVIR-randomized patients, 375 (38%) were DDDR paced at some time, accounting for 27% of follow-up days among all VVIR-randomized patients. Of 1,014 DDDR-randomized patients, 53 (5%) were VVIR paced at some time, accounting for 1.5% of follow-up days among all DDDR-randomized patients. On-treatment analyses showed slightly lower hazard ratios favoring DDDR versus VVIR compared with ITT: death or stroke 0.88 (on-treatment) versus 0.91 (ITT); death 0.94 versus 0.95; stroke 0.74 versus 0.81; HFH 0.72 versus 0.73; and AF 0.72 versus 0.77. Interpretation of treatment effects was unchanged. CONCLUSIONS: Although treatment crossovers accounted for >25% of follow-up time in the VVIR-randomized group, this did not affect study results. End point comparisons between randomized modes are accurate reflections of DDDR versus VVIR pacing in this study population.

Duke Scholars

Author Manesh Raman Patel Medicine, Cardiology

Author Kerry L. Lee Biostatistics & Bioinformatics, Division of Biostatistics