Novel endovascular baroreflex-amplifying implant lowers BP in therapy-resistant hypertension
Endovascular baroreflex amplification for resistant hypertension: a safety and proof-of-principle clinical study
Resistant hypertension, defined as uncontrolled blood pressure (BP) despite treatment with three or more drugs including a diuretic, and the associated increased CV and renal complication risk, occurs in about 10% of all treated hypertensive patients. Devices have been developed to treat resistant hypertension, but none has thus far been adopted for routine care .
Stimulation of the carotid baroreflex pathway, thereby amplifying the signal sensed by the carotid baroreceptors, results in inhibition of sympathetic outflow, and consequently a decrease in BP . As a less invasive alternative to implantable pulse generators that stimulate the carotid baroreceptors , the MobiusHD device has been developed, an endovascular implant that reshapes the carotid sinus. It yields in increased wall strain in the carotid sinus, which is sensed as increased pressure by the baroreceptors. The baroreceptors then respond by inhibiting sympathetic outflow and reducing BP . In an acute study in dogs, the MobiusHD device induced a more pronounced increase in carotid sinus nerve activity than a standard carotid stent and BP was lowered by around 50/30 mmHg for up to 6 hours. Long-term efficacy could not be assessed in the canine model.
This CALM-FIM_EUR study is a prospective first-in-human open-label study to assess the safety and efficacy of the MobiusHD in 30 patients with resistant hypertension who underwent carotid angiography (mean office SBP >160 mmHg, mean ambulatory SBP >130 mmHg for at least 30 days despite >80% treatment adherence to at least three antihypertensive drugs). The primary endpoint was the incidence of serious adverse events, including unanticipated adverse device effects at 6 months.
- Implantation of MobiusHD was successful in all patients, in the right internal carotid artery in 19 and in the left in 11 patients.
- Five serious adjudicated adverse events that were deemed to be possibly related to the procedure of device, occurred in four patients, but none were classified as unanticipated device effects (see original article for details and management).
- No device migrations and no significant changes in plaque formations in the carotid arteries were observed. The most frequently reported adverse event was dizziness (n=9 out of a total of 42 events), musculoskeletal pain (n=7) and hypotension (n=5).
- During the first 24 hours after implantation, a mean reduction of office BP of 38/23 mmHg (95%CI: 29-46/16-29) was seen.
- Mean reductions in office BP from baseline during follow-up were 27/14 mmHg (18-37/8-21) at 1 week, 22/10 mmHg (12-31/3-16) at 1 month, 24/11 mmHg (12-35/4-18) at 3 months, and 24/12 mmHg (13-34/6-18) at 6 months.
- Reductions in 24h mean ambulatory BPs were 15/8 mmHg (7–23/3–13) at 3 months and 21/12 mmHg (14–29/7–16) at 6 months (all p<0·002 in the overall ANOVA, and reaching p<0·0001 for SBP and DBP at 6 months).
- 22 (73%) patients met predefined criteria for clinically important BP-lowering response.
- The median number of antihypertensive medications was 0.50 lower (IQR: 1.25 – 0, P=0.0020) at 6 months and the daily defined doses was lowered by 0.42 units (2.13 to 0.09, P=0.10).
This first-in-man study of a novel endovascular baroreflex amplification device resulted in clinically important reductions in office and 24hrs ambulatory BP with acceptable safety, in patients with resistant hypertension. Most patients needed fewer medications after 6 months of follow-up.
This study has limitations inherent to a small, non-blinded set up, thus the safety profile and efficacy of the Mobius HD needs to be studied further in larger studies with longer follow-up.