Mark J. Caulfield 教授  英国Barts和伦敦，Queen Marry医学院， William Harvey 研究所和Barts 心血管生物医学研究所主任
　　<International Circulation>: Resistant hypertension is a difficult condition for clinicians and renal denervation brings new hope for clinicians and patients with resistant hypertension. What are the recommendations for renal denervation in the new ESH hypertension guidelines presented at this meeting?
Prof. Caulfield: In the ESH guidelines and the position paper specifically on renal denervation， the European Society of Hypertension have taken a conservative evidence-based approach to this new technology for which we are still gathering data.
The trials that we have to-date are with a particular technology， the Symplicity system made by Medtronic， and that has observational data from a cohort of 150 patients followed out to three years for which there is durable evidence of safety providing the patients are selected on strict criteria. To be resistant you had to have a blood pressure >160mmHg systolic and be on three or more medicines. Indeed the people in the trials have been very hypertensive so these are people for whom the average systolic blood pressure is 178mmHg. In the Symplicity trial， many have been on five or more medicines. These are people who are running out of conventional therapies to help them.
The other thing that is really important and that the European Society would like to stress is that it is essential that physicians adequately exclude other reasons for resistance. They can be due to secondary causes such as abnormalities of the adrenal glands or the kidneys that could be the root cause of the hypertension which would require a specific and different treatment. Those need to be rigorously excluded by a hypertension expert before consideration for this therapy. Typically we would expect the patient to be on three or more antihypertensives and have the criteria of the trial data sets that we have seen so far. This is very important because in this so-called resistant group there will be people who have secondary causes which are undiagnosed. There may also be people with undiagnosed white coat hypertension. This is where there is a blood pressure alerting response associated with going to see the doctor and clinician. So making sure of their ambulatory blood pressure is also important to confirm that they really are resistant.
The next important thing to consider is that some of our patients don’t always take their medicines and we really need to verify that people receiving this procedure are already consuming the medicines we believe they are because we don’t have any evidence in patients who are not taking medicines that this therapy is safe and effective.
The final group is a group of patients who don’t tolerate medicines well， who experience side effects and for whom this treatment might， with more evidence， offer a potential alternative to the side effects they experience with conventional therapies.
So we have taken a very conservative approach to this technology because we believe the evidence is growing but it is still in an early phase. This is really an important time for this and I think if people are deploying it， the ESH position paper and the ESH guidelines are a good framework. We think it’s exciting and has shown promise. It appears to be safe and durable and it appears to work， but not in all patients. Even in the trials， 15% of people did not respond to renal denervation. So one of the things clinicians need for the future is to be able to have perhaps a series of tests that they can deploy to allow them to understand which patients would most benefit from this therapy.
《国际循环》：难治性高血压对临床医生而言是个难题，肾脏去神经治疗则为医生及难治性高血压患者带来新希望。本次大会发布的新ESH指南对肾脏去交感神经治疗有何推荐？
Caulfield教授：目前，我们仍在不断收集肾脏去交感神经治疗的相关证据。在ESH指南以及ESH立场声明文件中，欧洲高血压学会（ESH）在对循证依据进行综述分析后对这项新技术持保守态度。
目前我们已经进行的试验主要来自于美敦力Symplicity系统的观察性数据，该试验入选150例难治性高血压患者，对其进行为期三年的随访，以探讨其长期安全性。其入选标准非常严格，难治性高血压患者的血压必须>160 mm Hg且曾应用至少三种药物治疗后无法降压达标。事实上，试验入选的患者血压非常高，其平均收缩压达178 mm Hg。在Symplicity试验中，很多患者应用的降压药物数量为至少5种，这些患者应用常规治疗方法已经无法达到控制血压。
另一个ESH要强调的非常重要的事情是，医生需要充分地排除其他原因所导致的难治性高血压。肾上腺或肾脏异常等继发性因素也能够导致难治性高血压，而此时需要采用不同的特异性治疗。因此，难治性高血压患者在行肾脏去交感神经治疗之前需要由高血压专家严格排除上述情况的存在。通常情况下，我们希望入选的患者选用三种或三种以上的降压药物。这是非常重要的，因为在所谓的难治性高血压患者中有一部分会伴有未确诊的继发性因素。也可能有一部分患者患有未确诊的与见到医生后紧张有关的白大衣高血压。因此，对这部分患者要进行动态血压检测来确定是否其真的患有难治性高血压。
另一件需要考虑的非常重要的问题就是，有些患者并未坚持服药。因此，在行肾交感去神经治疗前我们需要确保患者已经服用了药物。因为我们目前尚无证据表明在不接受药物治疗的患者中，肾脏去交感神经治疗同样安全有效。
另一种情况是因药物副作用而无法很好地耐受药物治疗的患者。越来越多的证据表明，对这类患者而言，肾脏去交感神经治疗是避免传统治疗副作用的潜在替代之选。
我们对这种新技术持保守态度，因为我们认为虽然其应用证据不断增多，但仍处于早期阶段。我认为，ESH立场声明及ESH指南为我们应用和发展这一新技术提供了很好的框架。我认为，这一新技术是非常令人兴奋的，也具有极大的发展前景。它看起来非常安全、持续性好，具有良好的疗效，但并不是对所有患者均有效。即使是在试验中，也有15%的患者对肾脏去交感神经治疗无反应。因此，未来临床医生需要做的就是开展一系列的试验来确定肾脏去交感神经治疗能为哪些患者带来最大获益。
　<International Circulation>: Renal denervation has been in rapid development in recent years. What are your thoughts on its long-term safety and efficacy?
Prof. Caulfield: Devices have a more rapid transition to use in clinical practice than medicines. I think we need a lot more data to be absolutely certain of long-term safety and durability but the data that we have on an observational cohort of 150 people in a randomized trial followed for two years and three years respectively， suggest that the therapy after it has been successfully delivered， is durable， safe and effective. Actually there don’t appear to be any long-term complications of it. But it really is too early to be absolutely certain of that; so we do need more evidence and we do need careful and restricted deployment of the technology at the present time which accords precisely with the evidence base that we have. This is not something we should be doing to all patients with high blood pressure at the moment. If you contrast renal denervation to conventional drug therapies， around the world many drug therapies and medicines that we use usually every day in clinical practice， are in fact only adopted for use on prescription on a regular basis once they have an extensive evidence base which is considerably greater than what we currently have for this.
But it is a technology with great promise and I think that presently in our patients where the blood pressure lowering pipeline of new medicines is pretty lean， we could conceivably do a therapy which might avoid people having to take more medicines every day. It could be a one-off procedure; we don’t yet know. If that would be the case then the potential for this， even expanding beyond its current indications for resistant hypertension is quite strong.
《国际循环》：近年来肾脏去交感神经治疗快速发展，您对其长期安全性及疗效有何看法？
Caulfield教授：与药物相比，器械向临床实践的转化速度更快。我认为我们需要更多有关其长期安全性及持久性的肯定性数据。对150例患者的随机试验随访2年及3年的观察性结果表明，肾脏去交感神经治疗是持久、安全和有效的，且似乎并无任何长期并发症。但是现在做出绝对的结论还为时尚早，我们需要更多的证据。基于目前的证据，我们目前仍需要谨慎地限制其应用。同时，目前并不是有所高血压患者均应使用该技术。将其与传统药物治疗相比较，你会发现，我们临床实践中通常每天应用的很多药物治疗，都是在药物有了充分证据的前提下开始应用的。
肾脏去交感神经治疗是一项非常具有前景的技术，我认为目前降压新药的研发非常有限，我们可以想见能够有一种能够使患者免于每天应用多种药物的治疗方法。但我们尚不得知它是否是个一次性过程。如果是的话，受益人群将非常有可能扩展到其当前适应证难治性高血压之外。