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去肾交感神经术治疗难治性高血压安全有效
作者:小柯机器人 发布时间:2022/9/21 13:25:45

美国布列根和妇女医院Deepak L Bhatt团队研究了去肾交感神经术治疗难治性高血压的远期疗效。相关论文于2022年9月18日发表在《柳叶刀》杂志上。

SYMPLICITY HTN-3(控制不佳高血压患者的肾去神经)试验表明,在6个月的随访期内,SYMPLICITY系统(Medtronic,Santa Rosa,CA,USA)对难治性高血压患者安全但疗效不佳。这份最终报告介绍了36个月的随访结果。

SYMPLICITY HTN-3是一项在美国88个中心进行的单盲、多中心、假对照、随机临床试验。招募年龄在18-80岁,患有难治性高血压,服用三种及以上包括利尿剂在内的稳定、最大耐受剂量的药物,坐位办公室收缩压为160 mm Hg及以上,24小时动态收缩压135 mm Hg以上的患者,将其随机分配(2:1),使用单电极(Flex)经导管去肾交感神经术或假对照组。

最初的主要终点是去肾交感神经术组与假对照组相比,从基线检查到6个月,办公室收缩压的变化。在6个月的主要终点评估后,患者不再双盲,此时符合纳入标准的假对照组合格患者(办公室血压≥160 mm Hg,24小时动态收缩压≥135 mm Hg,仍需开三种及以上降压药)可以交叉接受去肾交感神经术。

研究组分析了原去肾交感神经术组和假对照组患者36个月前的血压变化,包括6个月后进行去肾交感神经术治疗的患者(交叉组)和未进行去肾交感神经术的患者(非交叉组)。为了比较去肾交感神经术组和假对照组,交叉组患者的随访血压值采用交叉前最近的双盲血压值进行插补。

研究组报道了去肾交感神经术组和假对照组的长期血压变化,并利用治疗血压范围分析中的时间来研究两组的血压控制。主要安全终点是全因死亡率、终末期肾病、严重栓塞事件、需要干预的肾动脉穿孔或剥离、血管并发症、与不依从药物无关的高血压危象住院或6个月内新发肾动脉狭窄超过70%的发生率。

2011年9月29日至2013年5月6日,研究组共筛选了1442名患者,其中535名(37%;210名[39%]女性和325名[61%]男性;平均年龄57.9岁)被随机分配:364名(68%)患者接受了去肾交感神经术(平均年龄57.9岁),171名(32%)患者接受了假对照(平均年龄56.2岁)。219例患者(原去肾交感神经术组)、63例患者(交叉组)和33例患者(非交叉组)有36个月的随访数据。

36个月时,去肾交感神经术组的办公室收缩压平均降低26.4 mm Hg,假对照组平均降低5.7 mm Hg,组间差异显著。36个月时,去肾交感神经术组组24小时动态收缩压平均降低15.6 mm Hg,假对照组平均降低0.3 mm Hg,组间差异显著。在没有插补的情况下,去肾交感神经术组在治疗血压范围内的时间(即血压控制更好)明显长于假对照组的患者(去肾交感神经术组为18%,假对照组为9%),尽管药物负担相似,但插补结果一致且显著。.

各治疗组的不良事件发生率相似,没有证据表明去肾交感神经术后出现晚期并发症。综合安全终点的分析截至48个月,包括全因死亡、新发终末期肾病、导致终末器官损伤的显著栓塞事件、血管并发症、肾动脉再干预和高血压急症,去肾交感神经术组为15%(352例中有54例),交叉组为14%(96例中有13例),非交叉组为14%(69例中有10例)。

研究结果表明,SYMPLICITY HTN-3试验的最终报告为术后36个月去肾交感神经术的安全性提供了全部证据。从手术后12个月到36个月,最初随机分配接受去肾交感神经术的患者与接受假对照的患者相比,血压下降幅度更大,血压控制更好。

附:英文原文

Title: Long-term outcomes after catheter-based renal artery denervation for resistant hypertension: final follow-up of the randomised SYMPLICITY HTN-3 Trial

Author: Deepak L Bhatt, Muthiah Vaduganathan, David E Kandzari, Martin B Leon, Krishna Rocha-Singh, Raymond R Townsend, Barry T Katzen, Suzanne Oparil, Sandeep Brar, Vanessa DeBruin, Martin Fahy, George L Bakris, Deepak L Bhatt, George Bakris, Sidney A Cohen, Ralph DAgostino, Murray Esler, John Flack, David E Kandzari, Barry Katzen, Martin Leon, Laura Mauri, Manuela Negoita, Suzanne Oparil, Krishna Rocha-Singh, Ray Townsend, Ziad Abbud, Tayo Addo, David Anderson, John Angle, Herbert Aronow, Anvar Babaev, Keith Benzuly, Somjot Brar, David Brown, David Calhoun, Paul Casale, Sheldon Chaffer, James Choi, Eugene Chung, Debbie L Cohen, Mark Creager, George Dangas, Harold Dauerman, Shukri David, Mark Davies, Eduardo de Marchena, Ali E Denktas, Chandan Devireddy, William Downey, Mark Dunlap, Daniel Fisher, John Flack, Magdi Ghali, Eric Gnall, Raghava Gollapudi, Mark Goodwin, Nilesh Goswami, Luis Gruberg, Rajiv Gulati, Anuj Gupta, Anjan Gupta, Hitinder Gurm, Jeffrey Hastings, Scott Kinlay, Robert Kipperman, Maurice Buchbinder, Ajay Kirtane, Richard Kovach, David Lee, Samuel Mann, Steven Marso, Fadi Matar, Ernest Mazzaferri, Farrel Mandelsohn, Issam Moussa, Timothy Murphy, Sandeep Nathan, Brian Negus, Sahil Parikh, Manesh Patel, Kirikumar Patel, Basil Paulus, George Petrossian, Alex Powell, Jacek Preibisz, Florian Rader, Otelio Randall, Mahmood Razavi, John Reilly, Jonathan Reiner, Michael Ring, Mark Robbins, Kevin Rogers, Nicolas Ruggiero, Renato Santos, William Little, John Schindler, Thomas Scott, Thomas Shimshak, Mehdi Shishehbor, Mitchel Silver, Jasvindar Singh, Kanwar Singh, David Slovut, Rick G Stoufer, Paul Teirsten, Thomas Todoran, George Vetrovec, Ron Waksman, Yale Wang, Sergio Waxman, Robert Wilkins, Khaled Ziada, Frank Zidar

Issue&Volume: 2022-09-18

Abstract:

Background

The SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) trial showed the safety but not efficacy of the Symplicity system (Medtronic, Santa Rosa, CA, USA) at 6 months follow-up in patients with treatment-resistant hypertension. This final report presents the 36-month follow-up results.

Methods

SYMPLICITY HTN-3 was a single-blind, multicentre, sham-controlled, randomised clinical trial, done in 88 centres in the USA. Adults aged 18–80 years, with treatment-resistant hypertension on stable, maximally tolerated doses of three or more drugs including a diuretic, who had a seated office systolic blood pressure of 160 mm Hg or more and 24 h ambulatory systolic blood pressure of 135 mm Hg or more were randomly assigned (2:1) to receive renal artery denervation using the single electrode (Flex) catheter or a sham control. The original primary endpoint was the change in office systolic blood pressure from baseline to 6 months for the renal artery denervation group compared with the sham control group. Patients were unmasked after the primary endpoint assessment at 6 months, at which point eligible patients in the sham control group who met the inclusion criteria (office blood pressure ≥160 mm Hg, 24 h ambulatory systolic blood pressure ≥135 mm Hg, and still prescribed three or more antihypertensive medications) could cross over to receive renal artery denervation. Changes in blood pressure up to 36 months were analysed in patients in the original renal artery denervation group and sham control group, including those who underwent renal artery denervation after 6 months (crossover group) and those who did not (non-crossover group). For comparisons between the renal artery denervation and sham control groups, follow-up blood pressure values were imputed for patients in the crossover group using their most recent pre-crossover masked blood pressure value. We report long-term blood pressure changes in renal artery denervation and sham control groups, and investigate blood pressure control in both groups using time in therapeutic blood pressure range analysis. The primary safety endpoint was the incidence of all-cause mortality, end stage renal disease, significant embolic event, renal artery perforation or dissection requiring intervention, vascular complications, hospitalisation for hypertensive crisis unrelated to non-adherence to medications, or new renal artery stenosis of more than 70% within 6 months. The trial is registered with ClinicalTrials.gov, NCT01418261.

Findings

From Sep 29, 2011, to May 6, 2013, 1442 patients were screened, of whom 535 (37%; 210 [39%] women and 325 [61%] men; mean age 57·9 years [SD 10·7]) were randomly assigned: 364 (68%) patients received renal artery denervation (mean age 57·9 years [10·4]) and 171 (32%) received the sham control (mean age 56·2 years [11·2]). 36-month follow-up data were available for 219 patients (original renal artery denervation group), 63 patients (crossover group), and 33 patients (non-crossover group). At 36 months, the change in office systolic blood pressure was –26·4 mm Hg (SD 25·9) in the renal artery denervation group and –5·7 mm Hg (24·4) in the sham control group (adjusted treatment difference –22·1 mm Hg [95% CI –27·2 to –17·0]; p≤0·0001). The change in 24 h ambulatory systolic blood pressure at 36 months was –15·6 mm Hg (SD 20·8) in the renal artery denervation group and –0·3 mm Hg (15·1) in the sham control group (adjusted treatment difference –16·5 mm Hg [95% CI –20·5 to –12·5]; p≤0·0001). Without imputation, the renal artery denervation group spent a significantly longer time in therapeutic blood pressure range (ie, better blood pressure control) than patients in the sham control group (18% [SD 25·0] for the renal artery denervation group vs 9% [SD 18·8] for the sham control group; p≤0·0001) despite a similar medication burden, with consistent and significant results with imputation. Rates of adverse events were similar across treatment groups, with no evidence of late-emerging complications from renal artery denervation. The rate of the composite safety endpoint to 48 months, including all-cause death, new-onset end-stage renal disease, significant embolic event resulting in end-organ damage, vascular complication, renal artery re-intervention, and hypertensive emergency was 15% (54 of 352 patients) for the renal artery denervation group, 14% (13 of 96 patients) for the crossover group, and 14% (10 of 69 patients) for the non-crossover group.

Interpretation

This final report of the SYMPLICITY HTN-3 trial adds to the totality of evidence supporting the safety of renal artery denervation to 36 months after the procedure. From 12 months to 36 months after the procedure, patients who were originally randomly assigned to receive renal artery denervation had larger reductions in blood pressure and better blood pressure control compared with patients who received sham control.

DOI: 10.1016/S0140-6736(22)01787-1

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)01787-1/fulltext

期刊信息

LANCET:《柳叶刀》,创刊于1823年。隶属于爱思唯尔出版社,最新IF:59.102
官方网址:http://www.thelancet.com/
投稿链接:http://ees.elsevier.com/thelancet