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Initial results from the SYMPLICITY HTN-3 trial tempered enthusiasm for the use of renal denervation for treatment-resistant hypertension. The results showed that Medtronic's system -- though safe -- was no better than a sham procedure for reducing office systolic blood pressure through 6 months.
ľֱ reached out to get the reactions of leading cardiologists about the news.
, Detroit Medical Center
"I do not think this is the end of renal denervation. This may just be the wrong approach and/or learning curve issues with rolling out the study to multiple operators. There is ample data that renal denervation reduces blood pressure in animal models and in smaller human trials, and there are at least 30 different methods being tested to denervate the renal arteries. As a participant in this trial, it was technically difficult to assure that the radiofrequency probe was oriented correctly and that it was touching the wall of the renal artery. This may have resulted in the energy being dissipated into the bloodstream instead of into the vessel. Also, the nerves are very deep and the energy level may not have been high enough to penetrate."
, Columbia University Medical Center/New York-Presbyterian Hospital
"This is a very surprising result, entirely unexpected. We must withhold judgment until we review the data in detail to gain insight as to whether any subgroups might benefit, and what this means for other renal denervation technologies. Most importantly, however, given the clear therapeutic effect renal denervation had in the earlier nonblinded SYMPLICITY studies, this result underscores that a sham-controlled trial is essential in this kind of investigation. The 'power of the placebo' cannot be overemphasized."
, Beaumont Health System
"In addition to being a huge disappointment for Medtronic and for other companies that are invested in the arena of resistant hypertension, this is an enormous disappointment to physicians and patients, who believed that there might be a new emerging treatment approach for refractory hypertension. ... At this point, it isn't clear if the failure of HTN-3 reflects a failure of renal denervation itself, or whether it reflects a failure of Medtronic's device. In the meantime, other companies with other devices (radiofrequency, high-frequency ultrasound, hypothermia, local injection of chemicals to ablate renal nerves) will be reconsidering their own programs. It is possible that renal denervation with another device will be effective for treating hypertension, even though Medtronic's device appears less effective for this purpose."
, Duke University Medical Center
"Of course, it's dangerous to speculate, but the fact that SYMPLICITY HTN-3 was so carefully done with blinding and scientific rigor could provide another example of why we need proper clinical trials. This seemed like a 'slam dunk,' but obviously when put to the true test, it hasn't yet made the grade. If the result stands up, imagine the implications of proliferation of the technology before finding out if the technology actually provides real benefit."
, John Ochsner Heart and Vascular Institute
"This is important, as there was a great amount of initial enthusiasm that this treatment may allow blood pressure (BP) to be controlled with less medication. Obviously, besides lowering BP, this therapy would have to be shown to reduce cardiovascular events and be cost-effective before it could ever be used in routine practice."
, Lenox Hill Heart and Vascular Institute of New York
"All new technologies have ups and downs, but this finding is very important. Since this was the first study in a North American population, and the first to use a sham procedure in control patients, the negative findings have to make U.S. physicians question whether this approach can really improve blood pressure the way we'd all hoped. This might also cause other companies to reconsider their plans for clinical trials of renal denervation. That would be a terrible shame. One company recently announced it's halting a trial that was about to start. This is a very clever and safe technique that should be studied fully, so we can understand how it might be used to help people."
, Cedars-Sinai Medical Center
"Implausibly large treatment effects observed in uncontrolled and unblinded studies are typically unreliable and seldom replicable in rigorously controlled randomized trials. That is the major lesson from the SIMPLICITY HTN-3 trial. If the data are too good to be true, they usually are! It is too soon to abandon this procedure. We need to scrutinize the data first. If the treatment effect is attributable entirely to a sham effect, then it is difficult to see a future for renal denervation."
, NYU Langone Medical Center
"The field of renal denervation had promise in the background of 'resistant hypertension.' The failure of this trial may be due to several factors. One is the pharmacologic treatment of resistant hypertension. In many cases the patient could be successfully managed with adjustment of drugs or doses. The other issue is clearly that resistant hypertension may be due to a variety of factors that would not have a robust response to renal denervation. I believe that the issue may not be 'dead,' but rather its use more limited to patients who have truly not responded to an appropriate regimen of anti-hypertensive agents. The fact that it met the safety endpoint is encouraging."
, Beth Israel Deaconess Medical Center
"While the 'top-line results' are certainly a setback in the development cycle for renal denervation, there is no question that this therapy affects blood pressure in certain individuals. There is obviously more analysis of the data obtained in this study. The challenge will now be to identify the right patients for this therapy and to determine the technical predictors of success. Nonpharmacologic treatments that control blood pressure will still remain of considerable interest given the size of the hypertensive population who are at risk for stroke, heart attack, and kidney failure. We still need methods to control resistant hypertension. Nevertheless, a major contribution of SYMPLICITY HTN-3 will be clinicians learning that many of these patients can achieve blood pressure control with medications and adopting the best practice models used in this trial."
, Johns Hopkins Hospital
"I am surprised by the news. Hard to comment expansively without seeing the actual data but certainly disappointing news, especially in light of the European data. Will obviously need to follow the patients beyond 6 months. Maybe the benefit will be seen at a later time period. Safety endpoint is good but efficacy is certainly paramount."
, Icahn School of Medicine at Mount Sinai
"It is obviously disappointing to hear this news, although I reserve judgment until the full data are presented. I still believe that we need to step back and better understand this trial and the results before we shut out so many patients who may benefit from this type of therapy."
, Baylor Scott & White Healthcare
"I think the cardiology and hypertension communities will be surprised at the preliminarily presented findings, based on previously reported and published studies to date. It is not unprecedented that a therapy believed to be helpful fails in a clinical trial; this simply reiterates the importance of well-performed trials, adequately powered for relevant clinical endpoints. Compared to prior studies of renal denervation, SYMPLICITY HTN-3 was much larger, had very rigorous entry criteria, including the first time that ambulatory blood pressure was evaluated (instead of simply office-measured blood pressure), and perhaps, most importantly, had a control group that was blinded to whether they received the therapy or not. This finding argues for avoiding the premature dissemination of therapies (whether medications or procedures) until they are thoroughly studied. This is sometimes difficult when the expectation of benefit is so high, and particularly when patients are aware of a therapy and are even calling to request it. In the short term, this means that renal denervation, although performed frequently in Europe and other parts of the world, will not be approved or available in the U.S. for the foreseeable future. There is still much to learn, and it is certainly possible that it ultimately will be performed in the U.S.
From the American Heart Association: