Background

Previous randomised renal denervation studies did not show consistent efficacy in reducing blood pressure. The objective of our study was to evaluate the effect of renal denervation on blood pressure in the absence of antihypertensive medications.

Methods

SPYRAL HTN-OFF MED was a multicentre, international, single-blind, randomised, sham-controlled, proof-of-concept trial. Patients were enrolled at 21 centres in the USA, Europe, Japan, and Australia. Eligible patients were drug-naive or discontinued their antihypertensive medications. Patients with an office systolic blood pressure (SBP) of 150 mm Hg or greater and less than 180 mm Hg, office diastolic blood pressure (DBP) of 90 mm Hg or greater, and a mean 24-h ambulatory SBP of 140 mm Hg or greater and less than 170 mm Hg at second screening underwent renal angiography and were randomly assigned to renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were blinded to randomisation assignments. The primary endpoint, change in 24-h blood pressure at 3 months, was compared between groups. Drug surveillance was done to ensure patient compliance with absence of antihypertensive medication. The primary analysis was done in the intention-to-treat population. Safety events were assessed at 3 months. This study is registered with ClinicalTrials.gov, number NCT02439749.

Findings

Between June 25, 2015, and Jan 30, 2017, 353 patients were screened. 80 patients were randomly assigned to renal denervation (n=38) or sham control (n=42) and followed up for 3 months. Office and 24-h ambulatory blood pressure decreased significantly from baseline to 3 months in the renal denervation group: 24-h SBP −5·5 mm Hg (95% CI −9·1 to −2·0; p=0·0031), 24-h DBP −4·8 mm Hg (−7·0 to −2·6; p<0·0001), office SBP −10·0 mm Hg (−15·1 to −4·9; p=0·0004), and office DBP −5·3 mm Hg (−7·8 to −2·7; p=0·0002). No significant changes were seen in the sham-control group: 24-h SBP −0·5 mm Hg (95% CI −3·9 to 2·9; p=0·7644), 24-h DBP −0·4 mm Hg (−2·2 to 1·4; p=0·6448), office SBP −2·3 mm Hg (−6·1 to 1·6; p=0·2381), and office DBP −0·3 mm Hg (−2·9 to 2·2; p=0·8052). The mean difference between the groups favoured renal denervation for 3-month change in both office and 24-h blood pressure from baseline: 24-h SBP −5·0 mm Hg (95% CI −9·9 to −0·2; p=0·0414), 24-h DBP −4·4 mm Hg (−7·2 to −1·6; p=0·0024), office SBP −7·7 mm Hg (−14·0 to −1·5; p=0·0155), and office DBP −4·9 mm Hg (−8·5 to −1·4; p=0·0077). Baseline-adjusted analyses showed similar findings. There were no major adverse events in either group.

Interpretation

Results from SPYRAL HTN-OFF MED provide biological proof of principle for the blood-pressure-lowering efficacy of renal denervation.

Funding

Medtronic.

中文翻译：

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在不使用降压药的情况下未控制高血压的患者中基于导管的肾脏神经支配术（SPYRAL HTN-OFF MED）：一项随机，假对照，概念验证的试验

背景

先前的随机性肾脏去神经支配研究未显示出持续降低血压的功效。我们研究的目的是评估在不使用降压药的情况下肾脏去神经对血压的影响。

方法

SPYRAL HTN-OFF MED是一项多中心，国际性，单盲，随机，假手术控制的概念验证试验。在美国，欧洲，日本和澳大利亚的21个中心招募了患者。符合条件的患者未接受过药物治疗或已停止使用降压药。办公室收缩压（SBP）为150 mm Hg或更高且小于180 mm Hg，办公室舒张压（DBP）为90 mm Hg或更高，平均24小时门诊SBP为140 mm Hg或以下的患者在第二次筛查时大于或小于170毫米汞柱的患者接受了肾脏血管造影，并随机分配至肾脏去神经支配或假手术对照。患者，护理人员和评估血压的人员对随机分配不知情。比较两组之间的主要终点，即3个月时24小时血压的变化。进行药物监视以确保患者在不使用降压药的情况下依从性。初步分析是在意向性治疗人群中进行的。在3个月时评估安全事件。该研究已向ClinicalTrials.gov，编号NCT02439749。

发现

在2015年6月25日至2017年1月30日之间，共筛选了353名患者。80例患者被随机分配至肾神经支配（n = 38）或假手术（n = 42），并随访3个月。肾脏去神经组的办公室和24小时动态血压从基线到3个月显着下降：24小时SBP -5·5 mm Hg（95％CI -9·1至-2·0； p = 0·0031 ），24-h DBP -4·8 mm Hg（−7·0至-2·6; p <0·0001），办公SBP -10·0 mm Hg（−15·1至-4·9; p ＝ 0·0004），并且办公室DBP -5·3mm Hg（-7·8至-2·7； p = 0·0002）。在假对照组中未见明显变化：24 h SBP -0·5 mm Hg（95％CI -3·9至2·9； p = 0·7644），24-h DBP -0·4毫米汞柱（-2·2至1·4; p = 0·6448），办公室SBP -2·3毫米汞柱（−6·1至1·6; p = 0·2381）和办公室DBP -0· 3毫米汞柱（-2·9至2·2； p = 0·8052）。两组之间的基线和基线24小时血压从基线开始的3个月变化的平均差异为：24小时SBP -5·0 mm Hg（95％CI -9·9至-0·2； p = 0·0414），24-h DBP -4·4 mm Hg（−7·2至-1·6; p = 0·0024），办公SBP -7·7 mm Hg（−14·0至- 1·5； p = 0·0155），以及办公室DBP -4·9 mm Hg（-8·5至-1·4； p = 0·0077）。基线调整后的分析显示了相似的发现。两组均无重大不良事件。

解释

SPYRAL HTN-OFF MED的结果为肾神经支配的降压功效提供了生物学原理的证据。

资金

美敦力。