Department of Interventional Cardiology, Piedmont Heart Institute, Atlanta, GA, USA.
EuroIntervention. 2021 Apr 2;16(18):e1496-e1502. doi: 10.4244/EIJ-D-20-01090.
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.
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.
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 (ClinicalTrials.gov Identifier: NCT02439775), RDN was determined to be superior regarding a hierarchical endpoint and a "winner" compared with sham control patients.
有多种具有不同临床相关性的终点可用于确定器械治疗的疗效。鉴于高血压试验中血压测量和药物变化的差异，我们对接受肾去神经治疗（RDN）的患者进行了一项随机、假对照试验的结果进行了赢-输比分析，这些患者尽管接受了常规降压药物治疗，但血压仍未得到控制。我们提出了一种新的、优先考虑的终点框架，用于确定与假对照相比 RDN 的治疗益处。
我们使用包含 24 小时平均动态收缩压（SBP）、诊室 SBP 和药物负担的优先分层终点，对 SPYRAL HTN-ON MED 先导研究数据进行了分析。扩展了广义成对比较方法（赢-输比）来检验该终点。分别使用 5mmHg 和 10mmHg 的临床相关阈值来比较动态和诊室 SBP，从而定义治疗的“赢家”和“输家”。对于总共 1596 对未配对的患者，在 1050 对中 RDN 组的患者是“赢家”，在 378 对中 RDN 组的患者是“输家”，168 对是平局。有利于 RDN 的赢-输比为 2.78（95%置信区间[CI]：1.58 至 5.48；p<0.001），相应的净效益统计量为 0.42（95%CI：0.20 至 0.63）。根据不同的血压阈值和药物依从性测试进行的敏感性分析得出了一致的结果。
赢-输比方法通过纳入更多以患者为导向的结果并优先考虑那些被认为最具临床重要性的终点，解决了先前的局限性。将这些方法应用于 SPYRAL HTN-ON MED 先导研究（ClinicalTrials.gov 标识符：NCT02439775），与假对照患者相比，RDN 被确定在分层终点和“赢家”方面更具优势。
