Rheos Device Equivocal in Resistant Hypertension

July 28, 2011

July 27, 2011 (Washington, DC) — Device therapy for patients with hypertension resistant to multiple antihypertensive agents appeared to safely lower blood pressure according to some measures but not others, in a randomized, controlled study [1].

In the Rheos Pivotal Trial, published today in the Journal of the American College of Cardiology with lead author Dr John D Bisognano (University of Rochester Medical Center, NY), treatment with the Rheos System (CVRx, Minneapolis, MN) failed to show a significant effect on six-month BP-lowering efficacy and procedural safety. But it did show significant benefit for 12-month efficacy and baroreflex-therapy–related and device-related safety.

However, an overall "positive" trial required the novel therapy, consisting of an implanted pulse generator and carotid-sinus leads that can lower blood pressure through stimulation of carotid baroreflex receptors, to meet all five of those co–primary end points.

There were some noteworthy observations supporting the Rheos device as a potentially effective therapy for such difficult-to-treat patients, according to the authors. Of the trial's 265 patients to be implanted with the system, those randomized to having the pulse generator activated within one month (the rest, a control group, had it turned on six months later) showed a 40% drop in "serious adverse events for hypertensive urgency" at six months.

And by 12 months, they note, all patients had achieved systolic BP reductions of up to 35 mm Hg compared with baseline, and systolic BP had fallen to 140 mm Hg or below in >50% of the population group.

Bisognano told heartwire that although the trial's results were "mixed," it was designed to look at the treatment in a broad group of patients with drug-resistant hypertension.

The technology is evolving, and the data we got from this trial suggest there's a bright future for this device. Future trials will be designed to find the right patient populations for it

"It would have been nice if all five end points had been positive instead of just three, but what the trial has enabled us to do is look at what patient populations this would be most effective in," he said. The group is planning subgroup analyses to determine the effects, if any, of echocardiographic heart function, laboratory markers, and comorbidities on the treatment's effectiveness.

Bisognano said the implantation's complexity is "probably somewhere between a pacemaker implantation and carotid artery surgery."

The published findings are consistent with preliminary data the group reported at the American College of Cardiology 2011 Scientific Sessions in March and covered then by heartwire .

As reported by heartwire about a year ago, the trial's data safety and monitoring board (DSMB) had announced that the trial was unlikely to show a short-term efficacy difference between those who had the device turned on early vs later. CVRx officials were in discussion with the FDA about what would be required of the device in the future to make it approvable. Bisognano said the company is also planning the next study of the device for this indication.

That DSMB announcement followed the withdrawal of a planned presentation at the American Society of Hypertension 2010 Scientific Meeting on the first few dozen patients from the trial.

The patients were randomized 2:1 in double-blind fashion, one month after device implantation, to have it activated right away (group A, n=181) or at six months (group B, n=84), with blinding continued until the 12-month follow-up. Eligibility required them to have failed to achieve their BP target, usually 140/90 mm Hg after adherence to maximal therapy with three antihypertensive agents, including a diuretic. On average, they were receiving 5.2 such medications and were followed for 21 months.

How the Rheos system works [Source: CVRx]

Regarding the co–primary end points, by intention to treat, 54% of patients in group A and 46% of those in group B (p=0.97) were "acute responders"--that is, they showed at least a 10-mm-Hg decrease in systolic BP six months after implantation.

In group A, 88% of patients could be called "sustained responders" (p<0.001) and so surpassed the prespecified threshold of 65% (based on rates expected from the literature); a sustained response meant they had to show a systolic BP drop of at least 10 mm Hg at 12 months and the change from month 6 to month 12 had to be at least half as great as the change in the first six months.

(In a prespecified "ancillary" analysis, mean changes in systolic BP reached -26 mm Hg for group A and -17 mm Hg for group B [p=0.03] at six months and -35 mm Hg and -33 mm Hg, respectively [p=0.57], at 12 months.)

The rate of freedom from procedural complications within 30 days of implantation was 74.8% (p=1.00), short of the prespecified threshold of 82% (based on the literature). Procedural complications were most often related to the implantation surgery itself, including carotid sinus lead placement. Three-fourths of them "resolved completely," according to the group.

The rates of freedom from adverse events related to baroreflex therapy itself between day 30 and the six-month follow-up were 91.7% in group A and 89.3% in group B (p<0.001). Among such events, "hypertensive emergency" occurred in 5.0% and 8.3%, respectively.

Overall, the rate of freedom from "all major hypertension-related and serious device-related adverse events" from day 30 to the 12-month follow-up was 87.2%, surpassing (p<0.001) the prespecified threshold of 72% (based on the literature).

"Overall, the data are very encouraging," Bisognano said. "There really aren’t any treatments for drug-refractory, resistant hypertension patients. The technology is evolving, and the data we got from this trial suggest there's a bright future for this device. Future trials will be designed to find the right patient populations for it."

The trial was funded by CVRx, from which Bisognano has received grant support and for which he serves as a consultant/advisor. Disclosures for the coauthors are listed in the paper.

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