Exploration of devices to treat resistant hypertension in progress
BOSTON — Despite recent setbacks, research and development on device therapy for treatment-resistant hypertension is proceeding, a hypertension expert said at the Cardiometabolic Health Congress.
Baroreceptor activation therapy and renal denervation are not yet approved for use in the United States, but both are approved in other countries and have demonstrated benefit in patients whose hypertension cannot be controlled by diet, lifestyle and medication, George L. Bakris, MD, FAHA, FASN, professor of medicine and director of the University of Chicago Medicine Comprehensive Hypertension Center, said during a presentation.
George L. Bakris
Baroreceptor activation therapy
Baroreceptor activation therapy works via electrodes around the carotid sinus and carotid baroreceptors that are activated by a battery-operated device, Bakris, a Cardiology Today Editorial Board member, said. “That stimulates the baroreceptors and, in a dose-dependent fashion, amplifies the response to the brain and lowers [BP]. Over time, when you turn the device on, you can see a very nice drop in [BP] as well as a drop in sympathetic tone. It is very reproducible.”
One advantage, according to Bakris, is that “unlike with renal denervation, you know in the [operating room], before you have even sewn up a patient what the response is.” Another is that the voltage can be titrated to lower BP and heart rate by different degrees, he said.
The first version of the device, the Rheos (CVRx), had a battery that lasted 6 months and a pair of glove-like extensions that wrapped around each carotid bifurcation, and required a procedure that took about 90 minutes, he said. That sufficed for proof-of-concept, but was too cumbersome for commercialization. So, a new version, the Barostim Neo, was developed.
“[The Barostim Neo] has a single electrode because the engineers figured out that [more than] 80% of the response was actually coming from the right carotid baroreceptor, not the left,” he said. The new version has a battery that lasts 3 or 4 years and requires 45 to 60 minutes to implant, he said.
In a pivotal trial, baroreceptor activation therapy reduced systolic BP by –32 mm Hg to –36 mm Hg at 12 months, he said. A recent analysis showed that reduction was sustained at 5 years, he added. Another trial of the therapy is to begin soon.
Baroreceptor activation therapy is also being studied for a possible indication for patients with HF. It is already documented to reduce left ventricular mass, Bakris said. In a substudy of 60 patients from the pivotal trial, LV mass was reduced by a mean of –15 g/m2 after 12 months of baroreceptor activation therapy.
The therapy has not yet been approved by the FDA because of the acute safety profile of the original device; for example, it has been associated with increased rates of hematoma at 30 days, Bakris said. He noted that most observed complications were related to the anatomy of the vessel as opposed to the device. However, at 2 years to 5 years, rates of system- and procedure-related complications, MI and stroke are very low, he said.
Renal denervation was considered a highly promising therapy for treatment-resistant hypertension because “we have surgical data from the 1950s that clearly show that it works,” Bakris said. “If you do studies that suggest it is not working, then either you have a procedural issue or you have missed something along the way.” For example, he said, one small pilot study of renal denervation had a range of norepinephrine spillover of 0% to 90%.
“One of the possible reasons that renal denervation did not work [in the SYMPLICITY HTN-3 trial] is that the procedure, while reproduced from earlier studies, was restrictive and not as extensive as could have been done,” Bakris said. “We now know from animal studies that were done subsequent to the presentation of these data that if you fully denervate, not just one renal artery, but [other renal arteries] and the branches, the standard deviation for norepinephrine spillover falls dramatically and you have a [more than] 90% reduction in norepinephrine spillover. Future studies … will probably have to short-circuit every main and branch artery in sight.”
Although the SYMPLICITY HTN-3 trial (Medtronic) failed to show benefit of renal denervation for the primary efficacy endpoint of change in office systolic BP as compared with a sham procedure, at least three companies have developed new catheters for renal denervation, and there will be studies in the future, he said. – by Erik Swain
For more information:
Bakris GL. Device Therapy and Resistant Hypertension. Presented at: Cardiometabolic Health Congress, Oct. 22-25, 2014; Boston.
Disclosure: Bakris reports receiving consulting fees from AbbVie, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Janssen Pharmaceuticals, Medtronic, Oreixgen and Relypsa.