American College of Cardiology 2009: Catheter-Based Renal Denervation Reduces Resistant Hypertension
ORLANDO, FLORIDA, March 30, 2009 — A new proof-of-concept study in 45 patients with resistant hypertension suggests that a brief catheter-based procedure can safely ablate renal sympathetic nerves and may provide persistent blood-pressure reduction.
In this open first-in-human trial, renal denervation caused "substantial and sustained" blood-pressure reduction without serious adverse events, specifically renal artery aneurysm or stenosis, or any change in kidney function.
"We saw an immediate and sustained reduction in blood pressure, which at the 6- to 12-month end of the study was around a 25 mm Hg systolic reduction," lead author Henry Krum, MD, from the Center of Cardiovascular Research and Education in Therapeutics at Monash University in Melbourne, Australia, told Medscape Neurology & Neurosurgery.
Substudies looking at norepinephrine spillover and ambulatory monitoring "confirm, I think, that what we're seeing is real, supporting the concept that 1, we really are lowering blood pressure, and 2, we're doing it via denervation of sympathetics," he said. "And it's simple and safe."
The results are published online March 30 in The Lancet, to coincide with their presentation at the American College of Cardiology 58th Annual Scientific Session.
Renal sympathetic efferent and afferent nerves are crucial for the initiation and maintenance of systemic hypertension, the authors wrote. The nerves lie within and immediately adjacent to the wall of the renal artery. The company sponsoring the trial has developed a catheter-based system using radiofrequency (RF) ablation to disrupt renal sympathetic nerves without affecting other abdominal, pelvic, or lower-extremity innervation (Symplicity; Ardian, Palo Alto, CA).
During the procedure, the tip of the catheter is directed into the distal renal artery and 2 minutes of RF energy is applied, Dr Krum said. "The tip is withdrawn, circumferentially rotated within the artery, and a further 2 minutes of energy is applied, and so on all the way back through the renal artery, so in the end there's usually about 4 to 6 applications of the RF energy," he said. The first 10 patients in this open trial had staged procedures, but the remaining patients had bilateral ablations.
They enrolled 50 patients from 5 Australian and European centers. All had resistant hypertension, defined as a systolic blood pressure of more than 160 mm Hg on 3 or more antihypertensive medications including a diuretic. Five patients were subsequently excluded for anatomical reasons, mainly the presence of dual renal artery systems.
Patients received treatment between June 2007 and November 2008, with follow-up to 1 year. The primary end points were office blood pressure and safety data, taken prior to and then at 1, 3, 6, 9, and 12 months after the procedure. Renal angiography was done before, immediately after, and 14 to 30 days after the procedure, as well as magnetic resonance imaging at 6 months. Blood-pressure lowering was assessed using repeated-measures analysis of variance. A subgroup of patients was studied using renal noradrenaline spillover to assess the effectiveness of the renal sympathetic denervation achieved.
Among the treated patients, the baseline mean office blood pressure was 177/101 mm Hg (standard deviation, 20/15 mm Hg) while on a mean of 4 to 7 antihypertensive medications. The estimated glomerular filtration rate was 81 mL/min/1.73m2, and mean reduction in renal noradrenaline spillover was 47% (95% CI, 28%–65%).
In terms of safety, there was 1 intraprocedural renal artery dissection that occurred prior to the delivery of the RF energy, with no further sequelae. There were no other renovascular complications.
Blood-pressure reductions were seen among the treated patients at all time points, beginning as soon as 1 month after the procedure. By comparison, blood pressure continued to rise among the 5 patients who were excluded from the procedure.
Individually, however, not all patients responded to therapy. If response was defined as a blood-pressure reduction of 10 mm Hg systolic or greater, 83% of patients responded, Dr Krum noted. For the other 17% of patients, it is possible that either they were not adequately denervated, that renal sympathetic activation was not part of their hypertension process, "or potentially both," he said. However, they were not able to find any baseline predictors of response versus nonresponse in this small trial.
The next step will be a randomized trial, he said, although it is not clear at this point whether the comparator would be a sham procedure or simply randomizing these patients to usual care.
In a comment accompanying the paper, Michael Doumas, MD, from the Hypertension and Cardiovascular Research Clinic at the Veterans Affairs Medical Center and George Washington University in Washington, DC, and Stella Douma, MD, from the Hippokration Hospital and Aristotle University of Thessaloniki in Greece, called the study by Krum et al a "breakthrough study that opens up new avenues in the treatment of resistant hypertension."
The blood-pressure reduction was "impressive," and no adverse events were observed, they wrote. "Renal denervation itself does not seem to raise safety flags, because it occurs in kidney transplantation and seems to be of minor importance."
They give credit to the investigators for doing such a study "and the elegant and demanding techniques they used [noradrenaline spillover] to support their findings," they wrote. However, not all studied patients responded to treatment, they pointed out, "which underlines the need to identify predictors of blood-pressure reduction."
The procedure is minimally invasive, though, and interventional radiologists and cardiologists are already familiar with accessing the renal artery and using RF ablation, so that "we could rationally assume that the new technique might be widely used, if proven effective and safe in large randomized trials."
They concluded that this approach, although promising, cannot be considered a first-line option for treatment but should be reserved for those who have hypertension that is truly resistant to drug therapy. Further research is also required to better identify those who may benefit from this intervention, they added.
"However, we feel that our questions will soon be answered and our concerns eliminated," Drs Doumas and Douma concluded. "Therefore, we strongly believe that Krum and colleagues provide hope for the management of a difficult clinical condition."
However, Dr Krum was uncertain why, if it is found to be safe and effective in randomized investigation, it should not be considered at some point first-line treatment as an alternative to lifelong medical therapy.
"Certainly that would be a starting point, but I think there might be great potential even in patients who have less severe forms of hypertension," he said in an interview. "We have no data on that, but I think we would be remiss if we didn't explore that area, because we're talking about something that's very simple—it's a 40-minute-odd procedure that produces these sustained reductions and could get patients off polypharmacy potentially."
Source: Medscape Medical News
