CHICAGO (EGMN) – Deactivating the renal sympathetic nerves via a catheter-based procedure achieved impressively large and durable reductions in blood pressure in the first randomized, multicenter trial of the novel therapy in patients with resistant hypertension.

The renal sympathetic denervation procedure was straightforward and safe, and the sizeable reduction in blood pressure was maintained throughout the scheduled 6 months of follow-up. In patients treated earlier outside of the clinical trial, blood pressures have continued to drift slightly lower through 2.5 years of follow-up, raising the possibility that this procedure provides once-and-for-all treatment, Dr. Murray D. Esler said at the annual scientific sessions of the American Heart Association.

The primary endpoint in the 106-patient Symplicity HTN-2 trial was office-based blood pressure at 6 months. There was a mean 32/12 mm Hg reduction from a baseline of 178/96 mm Hg in patients in the renal denervation arm, all of whom remained on multidrug therapy. Home and ambulatory blood pressure readings followed suit, although the measured reductions were less robust.

In contrast, blood pressure was unchanged over time in patients in the control arm, even though they remained on optimally dosed multidrug antihypertensive therapy, according to Dr. Esler, associate director of the Baker IDI Heart and Diabetes Institute in Melbourne, Australia.

The encouraging results of Symplicity HTN-2 open the door to an entirely new approach to resistant hypertension, one that sidesteps the expense of lifelong therapy with multiple antihypertensive agents, the inherent limited efficacy of the drugs currently available, and compliance issues that commonly arise with multidrug therapy for a silent disease, he added.

Renal denervation therapy could be widely applicable. Roughly 15%-20% of hypertensive patients have resistant hypertension as defined by blood pressures remaining above target in spite of optimal doses of at least three antihypertensive agents, one of which should be a diuretic. This was the population enrolled in Symplicity HTN-2; in fact, nearly two-thirds of participants were on at least five antihypertensive drugs.

Future trials will evaluate renal denervation in milder forms of essential hypertension, as well as in other diseases involving activation of renal sympathetic outflow, including heart failure, cirrhosis with ascites, and chronic kidney disease.

The denervation procedure entails using standard endovascular technique to pass a proprietary radiofrequency catheter via femoral access into the renal artery lumen. The operator then delivers four to six bursts of low-power radiofrequency energy along the length of each renal artery to ablate the renal nerves, located in the adventitia of the renal artery. This results in decreased whole-body noradrenaline spillover, increased renal blood flow, and reduced plasma renin activity, the investigators noted in a published report released online simultaneously with Dr. Elser’s presentation (Lancet Nov. 17, 2010 [doi: 10.1016/S0140-6736(10)62039-9]).

No serious procedure-related complications occurred. Renal function remained unchanged during follow-up, even in patients who had mild to moderate renal impairment at baseline.

Blood pressure reductions of the magnitude achieved in Symplicity HTN-2 could, in theory, be expected to result in roughly 60% decreases in stroke and MI rates in these sorts of very-high-risk patients, according to Dr. Elser and others.

He said that the inspiration for the development of catheter-based renal denervation came from the earlier success of nonselective surgical sympathetectomy as a means of lowering blood pressure in severe hypertension in the days before modern antihypertensive drugs.

“In the current era, drugs blocking the renin-angiotensin system have moved to the fore and the sympathetic nervous system has kind of been swept into the shadows,” he noted.

A U.S. clinical trial of the device therapy will begin early next year. Meanwhile, the therapy is being introduced into clinical practice in Australia and Europe. Dr. Elser said he would not be surprised to see a turf battle between interventional cardiologists and interventional radiologists over who performs the procedure.

Discussant Dr. Suzanne Oparil said, “This is an extremely important study. It has a number of great strengths and the potential to really revolutionize the way we deal with treatment-resistant hypertension.”

The absence of adverse events, given the fact that 24 centers were involved in the trial, is a remarkable finding that speaks to the procedure’s safety and ease, observed Dr. Oparil, professor of medicine, physiology, and biophysics and director of the vascular biology and hypertension program at the University of Alabama, Birmingham. However, several limitations of the study were of concern, particularly the fact that only 17% of patients were being treated with aldosterone antagonists, which could be an indication that the patient population was not truly drug resistant.

Dr. Esler disclosed that he has received consulting fees and travel expenses from Ardian, which sponsored the Symplicity HTN-2 trial. Dr. Oparil is a consultant to Amylin, Boehringer-Ingelheim, Daiichi Sankyo, Forest Laboratories, Merck, NicOx, Novartis, and VIVUS.

Copyright (c) 2010 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

芝加哥(EGMN)——据一项在24所医学中心进行的随机试验显示，对顽固性高血压患者进行经导管去肾脏交感神经支配术可获得显著而持久的降血压疗效。

这项名为Symplicity HTN-2的试验共纳入106例顽固性高血压患者，试验组患者在进行去肾脏交感神经支配术后均坚持进行多药联合抗高血压治疗，对照组患者仅进行多药联合治疗(药物剂量配比经优化处理)。试验的主要终点是治疗6月后的血压值(诊室测量)。

患者基线时血压为178/96 mm Hg，试验组患者在第6月时血压平均下降32/12 mm Hg，但6月之后的降压效果不明显。不过，在本研究开始前便接受药物联合治疗的部分患者降压效果可一直持续到术后2.5年。对照组患者血压均无改变。据估测，实施该术可使患者卒中和心肌梗死(MI)的发病率降低约60%。

研究未发现手术相关并发症或不良事件，患者术后肾功能状况良好(包括基线时肾功能存在轻、中度受损的患者)，但在所有受试者中仅有17%之前接受过醛固酮拮抗剂治疗，将这一群体定义为耐多药顽固性高血压患者值得商榷。

高血压患者中约有15%~20%属于顽固性高血压(经至少3药联合治疗后血压仍旧超标)，现有抗高血压药物疗效有限，须终身服药且费用高昂，患者对其依从性较差，肾去交感神经术为顽固性高血压治疗带来了新希望，该术安全易行，疗效持久，有望为患者提供一劳永逸的治疗方案。

一位研究者表示接受了Symplicity HTN-2试验赞助方Ardian公司提供的咨询费和差旅费。另一位研究者在多家公司担任顾问。

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