WASHINGTON – As a result of remarkably sustained antihypertensive effect, interest is intensifying in the potential for a pivotal trial to associate a novel endovascular device with unprecedented blood pressure control in patients with treatment-resistant hypertension, according to an update presented at CRT 2019, sponsored by MedStar Heart & Vascular Institute.
With up to 3 years of follow-up, “systolic blood pressures have remained persistently reduced by as much as 24 mm Hg,” reported John P. Reilly, MD, an interventional cardiologist in Southampton, N.Y., who presented follow-up data for some of those enrolled in the first-in-human study of this device.
When the stent-like device is placed in the carotid artery, it alters its geometric shape, which increases pulsatile wall strain. The increase on wall strain alters an afferent signaling loop controlled by carotid baroreceptors that inhibits sympathetic outflow to lower blood pressure.
In the proof-of-principle, first-in-human CALM study, 47 patients were implanted with the device (MobiusHD, Vascular Dynamics). The initial study enrolled 30 subjects in Europe and 17 in the United States. Initial findings in the cohort of European patients, which included a mean 21–mm Hg reduction in systolic blood pressure and a 12–mm Hg reduction in diastolic blood pressure measured by ambulatory monitoring at 6 months, were published in the Lancet (2017 Dec 16;390:2655-661).
The patients enrolled in the proof-of-principle CALM trial were required to have highly-treatment-resistant hypertension, defined as a systolic blood pressure greater than or equal to 160 mm Hg despite at least three antihypertensive medications. The average number of medications was 4.4, according to Dr. Reilly. The mean blood pressure at entry was 165/98 mm Hg. Nearly 20% had previously undergone renal denervation.
The device was successfully deployed in all of the patients who participated in the open-label CALM study. Most of the 10 serious adverse events were related to hypotension, according to Dr. Reilly. Others included a wound infection and a case of intermittent claudication. Two instances of neurologic complaints, such as numbness and weakness, experienced within a day of device placement were considered potential transient ischemic attacks, but these resolved completely and no defects were observed on imaging.
In an update on CALM, Dr. Reilly reported that the large reductions in blood pressure previously reported at 6 months have been sustained. Follow-up is approximately 3 years in most patients, and the reductions previously reported have persisted in responders. When a clinically significant response is defined as a 10–mm Hg or more reduction in office blood pressure or 5–mm Hg or more reduction in ambulatory blood pressure, 75% of patients enrolled are still responding, but the more important point is that there has been no substantial reduction in blood pressure control over time in responders, according to Dr. Reilly.
When patients were stratified by a pulse pressure of greater or less than 70 mm Hg at study entry, response rates have been similar, he added.