At CIRSE 2011, in Munich, Germany, two experts told delegates what the evidence on renal denervation says so far, what studies ought to examine in the future, and what the potential downsides of the catheter-based treatment could be.
Willem P Th M Mali, Department of Radiology, University Medical Centre Utrecht, The Netherlands, who reviewed information from the recent trials on renal denervation, noted that as of April 2011, one international study group had investigated and published in three stages on the renal denervation technique.
Mali said that in the first step [Symplicity HTN-1], proof of principle and safety were shown in a cohort of 50 patients with treatment-resistant hypertension with one-year follow-up. Blood pressure was reduced at follow-up points of one, three, six, nine and twelve months. “There was a single complication of an intra-procedural renal artery dissection in one patient and this study showed that renal denervation can safely be used to reduce blood pressure in treatment-resistant hypertensive patients,” he said.
He then examined the second step [Symplicity HTN-2], the publication of a randomised controlled trial with data from106 patients with resistant hypertension. This study showed that at six months, 84% of the patients who underwent denervation had a reduction in systolic blood pressure of 10mm/Hg or more compared to 35% in the control group. “This randomised controlled trial showed that renal denervation can safely be used to substantially reduce blood pressure in treatment-resistant hypertension patients,” he said.
In the third step, Mali noted, investigators expanded the initial cohort of the first study to 153 patients (all with treatment resistant hypertension) to demonstrate that the blood-pressure lowering achieved with renal denervation was durable. “Blood pressure was observed to be reduced at the one, three, six, 12, 18 and 24-month stages. There were three pseudoaneurysms and one renal artery dissection and this study demonstrates that the results obtained with the procedure are durable,” Mali explained.
He also told delegates that the three studies described above had several limitations. “Up to now, the studies have not yet shown that the outcome of these patients have improved with respect to absolute (hard) outcome measures such as mortality, acute heart disease and stroke. Such outcome studies need to be carried out. Second, the patient population studied is very limited. It is quite likely that in patients with less severe hypertension, and less medication, renal denervation could prove a useful tool.
“In this respect, the problem of non-adherence to and non-persistence with a lifelong pharmacological therapy for a mainly asymptomatic disease should be addressed and the contribution of the denervation in a wide range of hypertension patients should be investigated. For these later studies, not only hypertension, but also long-term outcome measures should be studied,” he said.
Peter J Blankestijn, Department of Nephrology, University Medical Center, The Netherlands, who also spoke on the subject, stated that catheter-based renal denervation offers a fascinating new treatment modality because it deactivates the sympathetic nerves.
“For several years now it has been thought that the sympathetic overactivity is an important contributor to hypertension. Recently presented data provide sufficient rationale for further research on this method, and the way to do it is by careful and detailed long-term analysis of efficacy and safety variables in patients before and after the procedure. The procedure may also promote a better understanding of the underlying pathophysiology, thus helping define which type of patients will especially benefit from the procedure. Future research should also include cost-effectiveness analysis,” he said.
Are there any downsides to renal denervation?
Blankestijn told delegates that there is “obviously” concern about a detrimental effect on the anatomy of the renal arteries due to the invasiveness of the procedure. “Careful long-term follow-up of these patients is mandatory. Regeneration of nerve function is possible, especially for the efferent nerves, but afferent nerves are unlikely to re-grow. Any anatomical and functional regeneration will be difficult to diagnose apart from a rise in blood pressure. However, effects on afferent nerves are likely to be much more important, than effects on efferent nerves. It seems unlikely that there are unwanted effects with respect to short-term blood pressure regulation, since baroreceptor function is not affected. Since both afferent and efferent nerves may be destroyed, water and salt regulation may be altered. No data on the subject are available so far,” he said. He also noted that the procedure was still expensive.