Coronary interventions - Mini focus on biostatistics for clinical trials

Prioritised endpoints for device-based hypertension trials: the win ratio methodology

EuroIntervention 2021;16:e1496-e1502. DOI: 10.4244/EIJ-D-20-01090

David Kandzari
David E. Kandzari1, MD; Graeme L. Hickey2, PhD; Stuart J. Pocock3, PhD; Michael A. Weber4, MD; Michael Böhm5, MD; Sidney A. Cohen2, MD, PhD; Martin Fahy2, MS; Giuseppina Lamberti2, PhD; Felix Mahfoud5, MD
1. Department of Interventional Cardiology, Piedmont Heart Institute, Atlanta, GA, USA; 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, United Kingdom; 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

Aims: Multiple endpoints with varying clinical relevance are available to establish the efficacy of device-based treatments. Given the variance among blood pressure measures and medication changes in hypertension trials, we performed a win ratio analysis of outcomes in a sham-controlled, randomised trial of renal denervation (RDN) in patients with uncontrolled hypertension despite commonly prescribed antihypertensive medications. We propose a novel prioritised endpoint framework for determining the treatment benefit of RDN compared with sham control.

Methods and results: We analysed the SPYRAL HTN-ON MED pilot study data using a prioritised hierarchical endpoint comprised of 24-hour mean ambulatory systolic blood pressure (SBP), office SBP, and medication burden. A generalised pairwise comparisons methodology (win ratio) was 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 to define treatment “winners” and “losers”. For a total number of 1,596 unmatched pairs, the RDN subject was the winner in 1,050 pairs, the 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 [CI]: 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.

Conclusions: The win ratio method addresses prior limitations by enabling inclusion of more patient-oriented results while prioritising those endpoints considered most clinically important. Applying these methods to the SPYRAL HTN-ON MED pilot study ( Identifier: NCT02439775), RDN was determined to be superior regarding a hierarchical endpoint and a “winner” compared with sham control patients.

Sign in to read and download the full article

Forgot your password?

No account yet?
Sign up for free!

Create my pcr account

Join us for free and access thousands of articles from EuroIntervention, as well as presentations, videos, cases from

clinical trialsuncontrolled hypertensionrenal sympathetic denervation
Interventions for hypertensionRenal denervation
Read next article
Impact of clinical and haemodynamic factors on coronary flow reserve and invasive coronary flow capacity in non-obstructed coronary arteries: a patient-level pooled analysis of the DEBATE and ILIAS studies

Latest news