Renal Denervation Debate Tackles Efficacy, Patient Selection

Marlene Busko

October 24, 2013

MONTREAL, QC — Although the Symplicity renal denervation system (Medtronic) device is approved in Canada for treatment-resistant hypertension, strong evidence to support widespread use of this procedure is lacking, although that may come from SYMPLICITY HTN-3 , experts said here. An entertaining debate[1] at last week's Canadian Cardiovascular Congress (CCC) 2013 asked, "Is renal denervation ready for prime time?" There was no clear winner or loser—and no vote either—but the debate showed why this procedure remains a hot-button topic.

Interventional cardiologist Dr John Graham (Saint Michael's Hospital (Toronto, ON) tried to convince the audience that "catheter-based renal sympathetic denervation is a cost-effective adjunctive therapy for true resistant hypertension, and . . . I do believe it is ready for prime time."

But Dr Ross Feldman (University of Western Ontario, London), past president of the Canadian Hypertension Society, poked holes in his opponent's arguments. The bottom line is, he said, that "it's unclear to me what the effectiveness of the procedure is."

Reasons to Adopt This New Technology

Graham provided a step-by-step analysis for why renal denervation should be more widely adopted. In Canada, the prevalence of hypertension increased by 50% over the past decade[2]; it now affects one in five Canadians, and the diagnosis is associated with increased mortality, he said.

Resistance to antihypertensives—defined as above-target blood pressure despite compliance with three antihypertensive agents at a good dose including a diuretic—affects as many as one in 50 patients. A recent study from Kaiser Permanente[3] showed that "in a relatively short time—one and a half years—up to 2% of [newly diagnosed hypertensive] patients were resistant," he noted. Resistant hypertension was associated with an increased risk of cardiovascular events (hazard ratio 1.47).

The role of the sympathetic nervous system in systemic hypertension is well-known. But trials of open surgery sympathectomy for hypertension conducted in the 1930s and 1950s showed that patients who survived the surgery might live longer and have perfect blood pressure, but they had to lie in bed, and they were incontinent and impotent.

Then four years ago, the proof-of-principle SYMPLICITY HTN-1 trial reported striking results of a catheter-based renal-artery sympathetic denervation in 45 patients with treatment-resistant hypertension[4]. The follow-up SYMPLICITY HTN-2 trial randomized about 100 patients with treatment-resistant hypertension to either renal denervation or control. "Impressively, 84% of the percutaneously denervated patients had a >10-mm-Hg reduction in systolic blood pressure."

Still not convinced? Graham pointed to recent two-and-a-half year data presented at the recent American Hypertension Society meeting and three-year data presented at the recent European Society of Cardiology meeting—as reported in by heartwire —both showing durable reductions in blood pressure.

Finally, a just-published meta-analysis[5] of 31 drug trials and 23 renal-denervation trials reported an average ambulatory systolic blood-pressure drop of 12 mm Hg (in trials where the baseline ambulatory blood pressure was not a deciding factor for enrollment); this type of decrease in a middle-aged man is associated with about a 40% reduction in stroke and a 30% reduction in MI. "I think that using renal-denervation therapy as an adjunct to achieve that drop in blood pressure is beneficial," Graham concluded.

Reasons to Wait

"The topic is renal denervation for resistant hypertension," Feldman reminded the audience. "So the first question we need to ask ourselves is, 'What is resistance, really?' " A study on therapeutic inertia, where providers failed to increase therapy when treatment goals were unmet[6], "would suggest the resistance is not with the patients primarily, it's in us," he said. Sodium restriction and aldosterone antagonists (such as spironolactone) are "two very important forgotten modalities" in the field of resistant hypertension, he pointed out. Both have both been associated with dramatic reductions in blood pressure, comparable to the reductions seen with renal denervation.

The change in office blood pressure found in SYMPLICITY HTN-2—a decrease of 32/12 mm Hg—is impressive, but is it "real"? In a subset of ambulatory blood pressures, that difference was closer to 11/7 mm Hg, he explained. And the difference in the control group was 3/11 mm Hg. "So the impact of renal denervation on [systolic] blood pressure was 8 mm Hg—less than the effect of aldosterone antagonism, less than the effect of reducing sodium," he said. SYMPLICITY HTN-3, which will look at ambulatory blood-pressure changes in a larger number of patients, will help define the true impact of renal denervation, he added.

Moreover, there are not long-term safety data about hemodynamic stress, Feldman pointed out.

He concluded with a powerful finish, discussing a recent study of another type of blood-pressure device[7]. The mean systolic blood pressure was 178 mm Hg pretreatment, dropping to 168 mm Hg postprocedure and 160 mm Hg six months later. "Let's all agree that was a really effective procedure." He then revealed that the "procedure" was the insertion of a sham device. When the device was turned on, blood pressure dropped further, to 152 mm Hg. "Doing the procedure and not turning on the device was associated with a reduction in BP fully comparable to that of renal denervation. . . . So do you really need to do renal denervation?"

"I still think the jury is out," debate cochair Dr Blair O'Neill (University of Alberta, Edmonton) told heartwire following the debate. "I think it is an exciting, potential alternative, but I think there is more work to be done, and obviously there are other manufacturers that are coming out with other ways to do this." Alberta spends over $35 million related to treating hypertension, largely on outpatient care, recurrent physician visits, and multiple lifelong medications, he continued. "If you had something that would provide an alternative, that would be fantastic."

"We don't do it at our institution yet," cochair Dr Jafna Cox (Dalhousie University, Halifax, NS) added. "It's clearly an area that's capturing a lot of attention," especially since the early studies of renal denervation showed significant improvements in blood-pressure reduction.

Feldman disclosed that he was a consultant for Medtronic.


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