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

Area of Science:

• Cardiovascular Medicine
• Interventional Cardiology
• Hypertension Management

Background:

• Assessing device-based treatments for hypertension requires robust endpoints.
• Traditional hypertension trials face challenges with variable blood pressure measures and medication changes.
• Renal denervation (RDN) is a device-based treatment for uncontrolled hypertension.

Purpose of the Study:

• To propose and apply a novel, prioritised endpoint framework using a win ratio analysis.
• To determine the treatment benefit of RDN compared to sham control in patients with uncontrolled hypertension.
• To evaluate the efficacy of RDN in the SPYRAL HTN-ON MED pilot study.

Main Methods:

• Utilised data from the SPYRAL HTN-ON MED pilot study (sham-controlled, randomised trial).
• Employed a prioritised hierarchical endpoint: 24-hour ambulatory systolic blood pressure (SBP), office SBP, and medication burden.
• Extended generalised pairwise comparisons (win ratio) with clinically relevant thresholds for SBP changes (5 mmHg ambulatory, 10 mmHg office).

Main Results:

• A total of 1,596 unmatched pairs were analysed.
• The win ratio favoured RDN, with 1,050 'winner' pairs, 378 'loser' pairs, and 168 ties.
• The overall win ratio for RDN was 2.78 (95% CI: 1.58 to 5.48; p<0.001), with a net benefit statistic of 0.42 (95% CI: 0.20 to 0.63).
• Sensitivity analyses confirmed consistent results across different thresholds and adherence levels.

Conclusions:

• The win ratio method effectively incorporates patient-oriented outcomes and prioritises clinical importance.
• RDN demonstrated superiority over sham control in the SPYRAL HTN-ON MED pilot study based on the hierarchical endpoint.
• This approach provides a more comprehensive assessment of treatment efficacy for device-based interventions in hypertension.