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Renal Denervation for Resistant Hypertension: Dead or Alive?
Franz H. Messerli
As Sripal Bangalore, MD, and I wrote in our editorial in The New England Journal of Medicine, we should turn the page on resistant hypertension because that is probably not a good indication for renal denervation, for the time being. If you look at HTN-3 carefully, you can perhaps make the point that African Americans don’t respond well to renal denervation — white people do, younger people do, men do and those with a normal glomerular filtration rate do. However, these differences were not significant with the use of a superiority margin of 5 mm Hg or after adjustments for multiple comparisons, and the FDA would probably not give a label for younger, white males. Although it can be argued that only one device was tested in HTN-3 and that other devices may show clinical benefit in resistant hypertension, the same device was used in HTN-3 as was tested in SYMPLICITY HTN-1 and HTN-2 where we saw enormous benefits, similar to those observed in studies evaluating other devices.
Nevertheless, we should by no means close the book on renal denervation. We do not know whether denervation was achieved in these studies. It has been shown time and again that sympathetic activity is increased in certain patients. We should therefore focus our research efforts on the effects of renal denervation in indications such as left ventricular hypertrophy, atrial fibrillation, metabolic syndrome and, of course, HF, as well as hypertensive patients who have increased sympathetic activity.
Franz H. Messerli, MD
Director of the Hypertension Program, Mount Sinai-Roosevelt Hospital, N.Y.
Disclosure: Messerli reports serving as an ad-hoc consultant for Medtronic.
Vasilios Papademetriou
My belief is that renal denervation for resistant hypertension works. I base this on the large collection of background information and study data we’ve collected during the past century from research involving animal models, denervation in humans and surgical sympathectomy. These data suggest that interrupting the sympathetic nervous system works. Second, we have evidence that renal denervation results in attenuation of the renal sympathetic system, decreases norepinephrine spillover and the overall sympathetic outflow, and improves muscle sympathetic nerve activity. There are a lot of studies that show impressive BP reductions after renal denervation, somewhere between 25 mm Hg and 30 mm Hg and even up to 30 mm Hg and 34 mm Hg. Admittedly, these studies do not have controls, which is a serious limitation; however, this kind of BP reduction is not something we usually see in drug studies, nor can it be easily explained as a placebo effect.
Ultimately, I think renal denervation works if we achieve satisfactory — close to complete — fiber interruption. This is probably the single most important problem with HTN-3. From the details we received after its publication and from talking with investigators, it seems that incomplete denervation was the problem with the trial, which was likely due to the design of the catheter — single tip — and the lack of investigator experience. Otherwise, the study was well designed and had all the elements of a perfect study.
Vasilios Papademetriou, MD
Professor of Medicine, Georgetown University, Washington, D.C.
Director of Cardiovascular Research, Washington, D.C. VA Medical Center
Disclosure: Papademetriou was an investigator in the EnligHTN I trial and is a consultant for St. Jude Medical.