德国萨尔兰大学Felix Mahfoud团队研究了肾脏去神经支配疗法联合抗高血压药物的长期疗效和安全性。2022年4月4日，《柳叶刀》杂志发表了这一成果。

在使用降压药物的情况下，肾脏去神经支配疗法可以降低血压；然而，缺乏肾脏去神经支配随机试验的长期安全性和有效性数据。在这项预先指定分析中，研究组比较了肾脏去神经支配治疗组与假对照组在36个月内的血压变化、抗高血压药物使用和安全性。

这项随机、单盲、假对照试验纳入了来自美国、德国、日本、英国、澳大利亚、奥地利和希腊25个临床中心的患者，他们的高血压控制不佳，办公室收缩压在150 mmHg和180 mmHg之间，舒张压为90 mmHg或更高。符合条件的患者24小时动态收缩压在140 mmHg到170 mmHg之间，同时服用1-3种稳定剂量的降压药物至少6周。

患者接受了肾血管造影，并被随机分配（1:1）进行射频肾去神经或假对照治疗。患者和医生在12个月随访后揭盲，假对照组患者在12个月的随访完成后可以跨组。主要终点是肾脏去神经支配组和假对照组在6个月时24小时平均收缩压的治疗差异。对意向治疗人群进行统计分析。长期疗效通过36个月的动态和办公室血压测量进行评估。药物监测用于评估药物使用情况。对安全事件进行了长达36个月的评估。

2015年7月22日至2017年6月14日，在467名登记患者中，80名符合资格标准，并被随机分配接受肾脏去神经支配（38名）或假对照手术（42名）。肾脏去神经支配组的平均动态收缩压和舒张压较基线显著降低，在24个月和36个月时显著低于假对照组，尽管抗高血压药物的治疗强度相似。36个月时，肾脏去神经支配组的药物负荷为2.13种药物，假对照组为2.55种药物。

肾脏去神经支配组31例患者中有24例（77%）在36个月时仍坚持服药，假对照组27例患者中有25例（93%）。36个月时，肾脏去神经支配组的动态收缩压平均降低18.7 mmHg，假对照组平均降低8.6 mmHg，组间差异显著。36个月时，肾脏去神经支配组的平均动态舒张压比假对照组低5.9 mmHg，上午收缩压比假对照组低11.0 mmHg，夜间收缩压比假对照组低11.8 mmHg。未发生与肾脏去神经支配相关的短期或长期安全问题。

研究结果表明，与假对照组相比，射频肾脏去神经治疗在长达36个月的随访中产生了具有临床意义且持久的血压降低，与联合抗高血压药物无关，且无重大安全事件。肾脏去神经支配可为高血压患者的治疗提供一种辅助治疗方式。

附：英文原文

Title: Long-term efficacy and safety of renal denervation in the presence of antihypertensive drugs (SPYRAL HTN-ON MED): a randomised, sham-controlled trial

Author: Felix Mahfoud, David E Kandzari, Kazuomi Kario, Raymond R Townsend, Michael A Weber, Roland E Schmieder, Konstantinos Tsioufis, Stuart Pocock, Kyriakos Dimitriadis, James W Choi, Cara East, Richard DSouza, Andrew S P Sharp, Sebastian Ewen, Antony Walton, Ingrid Hopper, Sandeep Brar, Pamela McKenna, Martin Fahy, Michael Bhm

Issue&Volume: 2022-04-04

Abstract:

Background

Renal denervation has been shown to lower blood pressure in the presence of antihypertensive medications; however, long-term safety and efficacy data from randomised trials of renal denervation are lacking. In this pre-specified analysis of the SPYRAL HTN-ON MED study, we compared changes in blood pressure, antihypertensive drug use, and safety up to 36 months in renal denervation versus a sham control group.

Methods

This randomised, single-blind, sham-controlled trial enrolled patients from 25 clinical centres in the USA, Germany, Japan, the UK, Australia, Austria, and Greece, with uncontrolled hypertension and office systolic blood pressure between 150 mm Hg and 180 mm Hg and diastolic blood pressure of 90 mm Hg or higher. Eligible patients had to have 24-h ambulatory systolic blood pressure between 140 mm Hg and less than 170 mm Hg, while taking one to three antihypertensive drugs with stable doses for at least 6 weeks. Patients underwent renal angiography and were randomly assigned (1:1) to radiofrequency renal denervation or a sham control procedure. Patients and physicians were unmasked after 12-month follow-up and sham control patients could cross over after 12-month follow-up completion. The primary endpoint was the treatment difference in mean 24-h systolic blood pressure at 6 months between the renal denervation group and the sham control group. Statistical analyses were done on the intention-to-treat population. Long-term efficacy was assessed using ambulatory and office blood pressure measurements up to 36 months. Drug surveillance was used to assess medication use. Safety events were assessed up to 36 months. This trial is registered with ClinicalTrials.gov, NCT02439775; prospectively, an additional 260 patients are currently being randomly assigned as part of the SPYRAL HTN-ON MED Expansion trial.

Findings

Between July 22, 2015, and June 14, 2017, among 467 enrolled patients, 80 patients fulfilled the qualifying criteria and were randomly assigned to undergo renal denervation (n=38) or a sham control procedure (n=42). Mean ambulatory systolic and diastolic blood pressure were significantly reduced from baseline in the renal denervation group, and were significantly lower than the sham control group at 24 and 36 months, despite a similar treatment intensity of antihypertensive drugs. The medication burden at 36 months was 2·13 medications (SD 1·15) in the renal denervation group and 2·55 medications (2·19) in the sham control group (p=0·26). 24 (77%) of 31 patients in the renal denervation group and 25 (93%) of 27 patients in the sham control group adhered to medication at 36 months. At 36 months, the ambulatory systolic blood pressure reduction was 18·7 mm Hg (SD 12·4) for the renal denervation group (n=30) and 8·6 mm Hg (14·6) for the sham control group (n=32; adjusted treatment difference 10·0 mm Hg, 95% CI 16·6 to 3·3; p=0·0039). Treatment differences between the renal denervation group and sham control group at 36 months were 5·9 mm Hg (95% CI 10·1 to 1·8; p=0·0055) for mean ambulatory diastolic blood pressure, 11·0 mm Hg (19·8 to 2·1; p=0·016) for morning systolic blood pressure, and 11·8 mm Hg (19·0 to 4·7; p=0·0017) for night-time systolic blood pressure. There were no short-term or long-term safety issues associated with renal denervation.

Interpretation

Radiofrequency renal denervation compared with sham control produced a clinically meaningful and lasting blood pressure reduction up to 36 months of follow-up, independent of concomitant antihypertensive medications and without major safety events. Renal denervation could provide an adjunctive treatment modality in the management of patients with hypertension.

DOI: 10.1016/S0140-6736(22)00455-X

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00455-X/fulltext