The Symplicity III trial while reaching its safety endpoint did not reach its efficacy endpoint.
At Mercy Angiography we are currently involved with and recruiting patients for a very interesting trial where denervation is completely non-invasive and uses externally applied ultrasound to damage the renal sympathetic nerves. It seems very effective and does not seem to have side effects. This approach has much promise and patients appear to have nothing to lose as it is non-invasive and appears very safe and preliminary results show it is effective. A larger sham trial is being planned. Patients and staff do not know whether the patient is in the treatment or control arm. This is very easy to do with this non-invasive trial using ultrasound. After a period the control arm patients are given the option to have the treatment.
The European Society of Hypertension's comment on SYMPLICITY HTN -3 results: The Symplicity III trial where patients were randomized to renal denervation with the Symplicity device or a sham treatment failed to reach its primary efficacy endpoint. It was not better than the control arm.
"The European Society of Hypertension believes that although in the Symplicity HTN-3 study use of an appropriate control group makes the results less open to confounders than those of previous studies, the conclusion that renal denervation is ineffective is not justified.
One, given the multifactorial contribution of renal nerves to blood pressure elevation, renal denervation has a strong pathophysiological rationale.
Two, albeit in a less well controlled fashion, several studies have found renal denervation to be accompanied not only by sizeable blood pressure reduction, but also by an improvement of biomarkers that have been shown to be prognostically relevant in individuals with a blood pressure elevation .
Three, there are in the Symplicity HTN-3 study data, such as the greater blood pressure effects of renal denervation in non-African Americans, that suggest that the procedure may be effective in specific subgroups.
Thus, the reaction to the negative results of the Symplicity HTN-3 study should not be to abandon the renal denervation approach but to perform further studies of high scientific calibre that could provide further evidence on its overall position in the treatment of resistant hypertension, determine whether the blood pressure effects are limited to some patients' subgroups (and clarify their characteristics), and see whether and to what extent their blood pressure reductions translate into cardiovascular and renal protection. Although the true prevalence of resistant hypertension is still uncertain, there is no question that in an overall high number of individuals current drug treatment is not effective and that the risk of these individuals to develop cardiovascular and renal complications is high. This represents an important unmet therapeutic need that research should continue to address, without prematurely abandoning approaches that rationale and background preliminary data allow to consider one of the possible solutions."
1. Bhatt DL, Kandzari DE, O'Neill WW, D'Agostino R, Flack JM, Katzen MT, Leon MB, Liu M, Mauri L, Negoita M, Cohen S.A., Oparil S, Rocha-Sing K, Townsend RR and Bakris GL. A controlled trial of renal denervation for resistant hypertension. N Engl J Med 2014, published on March 29, doi:10.10567nejmoa1402670
2. Messerli FH, Bangalore S. Renal Denervation for Resistant Hypertension? N Engl J Med. 2014, published on March 29. [Epub ahead of print]
Professor John Ormiston
MBChB,FRACP,FRACR,FCSANZ,FAPSIC,FRCP, FACC, ONZM