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By Gene Emery and Bill Berkrot
PROVIDENCE, RI/WASHINGTON, March 29 Patients treated by renal artery denervation were no more likely to see their blood pressure decline than those who received a fake therapy in a major clinical trial, calling into question a therapy used in more than 80 countries to treat hypertension that doesn't respond to drugs.
The study was considered a key test of the intervention in which nerve connections between the heart and kidney were disrupted in an effort to lower blood pressure as prior trials did not include a blinded control group for efficacy comparison.
The study, released on Saturday by the New England Journal of Medicine and presented at the meeting of the American College of Cardiology (ACC) in Washington, "brings the renal-denervation train to a grinding halt," said Dr. Franz Messerli and Dr. Sripal Bangalore in a Journal editorial.
Because earlier tests of the technique did not involve treating some patients with sham therapy, "placebo effect may well explain all or most of the blood pressure differences" in two key trials, known as SYMPLICITY HTM-1 and HTN-2.
The new blinded test, called SYMPLICITY HTN-3, was financed by Medtronic Inc, which makes the equipment used in the study. Boston Scientific Corp and St. Jude Medical Inc also make renal denervation equipment.
"We wanted to see whether this would offer something beyond what the best medical therapy can," chief investigator Dr. Deepak Bhatt of Brigham and Women's Hospital in Boston said in a telephone interview. "It should give doctors pause to what they're doing, at a minimum."
Renal denervation involves threading a catheter into the arteries feeding the kidney and using radiotherapy to destroy some of the nerves believed to control blood pressure.
About 10 percent of people with high blood pressure are resistant to conventional therapy and are candidates for the treatment, which is still regarded as experimental in the United States. It is approved in parts of Europe, South America, Australia and Canada.
Given positive findings in prior trials, "it was a surprise to almost everyone that the results were negative," said Dr. Anthony DeMaria, who discussed the study at an ACC news conference but was not involved in the trial.
He said more evidence was needed to ensure that the procedure was actually accomplishing effective denervation.
Meanwhile, "I would limit it to patients who have no alternative," said DeMaria, director of the Cardiovascular Center at U.C. San Diego School of Medicine.
Among the 364 patients whose arteries were treated, systolic blood pressure was 14 mm Hg lower six months after the treatment, versus 12 mm HG lower among the 171 who had a renal angiogram but not the denervation procedure.
All patients were already taking at least three blood pressure medicines at maximum tolerated doses that had failed to bring the condition down to target levels.
There was also no significant difference in the drop in 24-hour ambulatory systolic blood pressure, which declined 7 mm Hg with treatment and 5 mm Hg in the sham group.
Medtronic vowed to move forward with its program.
"We remain convinced that resistant hypertension is a large unmet medical need and renal denervation remains a promising opportunity," Nina Goodheart, head of renal denervation for Medtronic, said in a statement.
The company said it will continue to provide access to its Symplicity system in countries where it is approved and will work with the U.S. Food and Drug Administration to determine a path forward in the United States.
While the company said further clinical investigation is warranted, it will discontinue a follow-up study that had been suspended and consult with local regulators to determine the future of trials in Japan and India.
"I think if we did this type of randomized, blinded trial, and with sham controls when you're talking about medical devices ... a lot of things that we think of as effective may not be effective," Bhatt said.
The researchers plan to follow the patients for up to five years to see if the treatment shows a delayed benefit.
There is still hope that a variant of the technique might be useful, Bhatt said.
"This trial was clearly negative, but I would hate to think that this kills the field of renal denervation," he said, noting that animal studies, clinical data and surgery used in the past show that disrupting the nerves between the kidney and the heart can lower blood pressure.
Earlier surgery had drastic side effects, which is why it was abandoned. "But somewhere between those two extremes I would hope there would be a sweet spot where we could potentially deliver enough energy to denervate and produce a clinically meaningful effect on blood pressure without those bad side effects of surgery," Bhatt said. (Reporting by Gene Emery; additional reporting by Bill Berkrot in Washington; Editing by James Dalgleish)