Baroreflex Activation Therapy (BAT) ® for the treatment of drug-resistant hypertension, using any carotid sinus stimulation device (e.g., Rheos Baroreflex Hypertension Therapy System®), experimental, investigational and unproven.Baroreflex Activation Therapy (BAT) using the Rheos Baroreflex Hypertension Therapy System was evaluated in a prospective double-blind pivotal phase III trial, with 265 patients who were randomized on a 2:1 basis from 49 sites. All patients had to have systolic BP of >160 mm Hg and/or diastolic BP >80 mm Hg, with 24-hour ambulatory BP monitoring (ABPM) readings of >135 mm HG and at least one month of maximally tolerated therapy with at least three appropriate antihypertensive medications, including a diuretic. The patients had a mean body-mass index (BMI) of 32 to 33, and they were taking an average of 5.2 antihypertensive therapies.
All patients were surgically implanted with the device, with group A, consisting of 181 patients, having the device turned on after one month. The remainder (n=84), group B, had the device implanted, but it was turned off for the first seven months. There were five co-primary end points: the short-term acute response six months after the device was turned on; the long-term sustained response; short-term procedural adverse events; short-term hypertension-therapy adverse events; and long-term device adverse events.
The first end point, short-term acute response, failed to reach significance in the on-treatment group, with 65% of patients in that group achieving the goal, a 10-mm-Hg reduction in systolic BP at six months, compared with 45% in the off-treatment group.
End point two, the long-term sustained response, did reach significance. However, only those in group A, the patients in whom the device was turned on a month after implantation, and not those in group B—in whom the device was turned on six months later—were assessed in this end point.
There were a number of adverse events relating to the surgical procedure to implant the Rheos system, and as a result, end-point three—short-term procedural adverse events—was not met. Overall, 75% of patients were free of procedural adverse events at 30 days, but the prespecified figure for this was 82%. In terms of adverse procedural events, 4.4% of patients had permanent nerve injury, 4.8% had transient nerve injury, 4.4% had general surgical complications, and 2.6% had respiratory complications. There were 76% of all adverse events fully resolved. The other two end points—long-term device safety and short-term therapy safety—were met. Study conclusions note that the weight of overall evidence suggests long-term efficacy of BAT to reduce BP in resistant hypertension, and that the data justifies further development.
Although results from the Rheos pivotal phase III trial are promising, additional studies are necessary to justify this new treatment modality. In addition, so far BAT has not been compared to drug therapy alone (i.e., without any device implantation) for controlling severe hypertension in clinical trials.