The Official Journal of EuroPCR and the European Association of Percutaneous Coronary Interventions (EAPCI)
Prioritized Endpoints for Device-Based Hypertension Trials: the Win Ratio Methodology
David Kandzari1; Graeme L. Hickey2; Stuart J. Pocock3; Michael A. Weber4; Michael Böhm5; Sidney A. Cohen2; Martin Fahy2; Giuseppina Lamberti2; Felix Mahfoud5;
1. Department of Interventional Cardiology, Piedmont Heart Institute, Atlanta, GA, USA, United States 2. Coronary and Structural Heart Division, Medtronic PLC, Santa Rosa, CA, USA 3. Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK 4. Department of Medicine, SUNY Downstate College of Medicine, Brooklyn, NY, USA 5. Department of Internal Medicine III, Klinik für Innere Medizin III, Kardiologie, Angiologie, Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Saarland University, Homburg, Germany
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Aims: Multiple endpoints with varying clinical relevance are available to establish the efficacy of device-based treatments. We propose a novel prioritized endpoint framework for determining the treatment benefit of renal denervation (RDN) compared with sham control.
Methods and Results: We analysed the SPYRAL HTN-ON MED pilot study data using a prioritized hierarchical endpoint comprised of 24-hour mean ambulatory systolic blood pressure (SBP), office SBP, and medication burden. A generalized pairwise comparisons methodology (win ratio) is extended to examine this endpoint. Clinically relevant thresholds of 5 and 10 mmHg were used for comparisons of ambulatory and office SBP, respectively, and therefore define treatment ‘winners’ and ‘losers’. For a total 1596 unmatched pairs, the RDN subject was the winner in 1050 pairs; RDN subject was the loser in 378 pairs; and 168 pairs were tied. The win ratio in favour of RDN was 2.78 (95% confidence interval, 1.58 to 5.48; P<0.001) and corresponding net benefit statistic was 0.42 (95% CI, 0.20 to 0.63). Sensitivity analyses performed with differing blood pressure thresholds and according to drug adherence testing demonstrated consistent results.
Conclusion: The win ratio method addresses prior limitations by enabling inclusion of more patient-oriented results while prioritizing those endpoints considered most clinically important. Applying these methods to the SPYRAL HTN-ON MED pilot study, RDN was determined superior regarding a hierarchical endpoint and a ‘winner’ compared with sham control patients