Adjudicating Heart Failure Events in Participants Receiving Hemodialysis: Findings from Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) Trial.

INTRODUCTION

The Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial compared the effects of cinacalcet against placebo on major cardiovascular events in 3,883 hemodialysis patients with secondary hyperparathyroidism. In this manuscript, we describe heart failure events in EVOLVE and the role of centralized adjudication on heart failure reporting.

METHODS

A central clinical events classification committee (CEC) defined and adjudicated suspected heart failure events reported by the site investigators. The treatment effect was analyzed by intention to treat.

RESULTS

Overall, 3,883 participants were enrolled, 1,366 heart failure events were reported by site investigators, and 40 potential events were identified independently by the CEC. Among site investigator-reported events, 653 (47.8%) were adjudicated by the CEC as heart failure endpoints. Of the 40 potential events identified independently by the CEC, 17 (42.5%) were adjudicated as heart failure endpoints. The effect of cinacalcet compared with placebo on time to first heart failure event using CEC-adjudicated and site investigator-reported events (10.6% and 12.2% for CEC-adjudicated events [relative hazard 0.82, 95% CI: 0.68-0.99] and 20.3% and 22.1% for site investigator-reported events [relative hazard 0.88, 95% CI: 0.77-1.01]) was similar, although CEC data included fewer events but nominally statistically significant results.

CONCLUSION

Roughly half of heart failure events reported by site investigators were not adjudicated as heart failure by the CEC. Site investigators failed to report additional events that were later adjudicated as heart failure endpoints. These findings suggest that, in the hemodialysis population, identifying and classifying heart failure events is challenging and highlight the importance of centralized adjudication to ensure specificity and consistency in clinical events ascertainment.