Effect of baroreflex activation therapy on blood pressure: the bat-study – a randomized sham clinical pilot trial

Objective: To explore the effects of baroreflex activation therapy (BAT) on blood pressure in individuals with refractory hypertension. Design and method: This investigator-initiated randomized, double-blinded sham-controlled pilot trial included five Finnish patients with refractory hypertension. Participants were found eligible if they were 18 - 70 years old with a daytime systolic ambulatory blood pressure (ABP) of 145 mmHg or higher, and/or a daytime diastolic ABP of 95 mm Hg or higher. Patients were on 3 or more antihypertensive drugs including a diuretic. A witnessed drug intake prior to ABPM was implemented. The Barostim Neo System was implanted for modulation of the autonomic nervous system by direct electrical stimulation of the carotid baroreceptors. After 1 month following implantation, all participants were randomized to either 8 months of baroreflex activation therapy (BAT-system on) or continuous pharmacotherapy (BAT-system off) followed by continuous BAT-therapy for all participants for 8 months. The complete design is outlined in the Figure. 24-hour ABP-measurements were performed per protocol. The primary outcome was defined as a change in ambulatory systolic blood pressure after 8 months of BAT, compared to pharmacotherapy. Results and conclusions: After 8 months of follow-up BAT decreased mean systolic daytime blood pressure by 11.8 mmHg in three participants randomized to BAT, while in the two remaining participants randomized to continuous pharmacotherapy mean systolic daytime blood pressure increased by 8.7 mmHg. When pooling all daytime systolic 24-hour ABP-measurements across the entire follow-up, BAT-therapy was associated with a 9.2 mmHg lower mean blood pressure as compared to continuous pharmacotherapy (143.5 mmHg [95% CI:142.2 - 144.9] vs 152.7 mmHg [151.1 - 154.2], P < 0.0001). In linear mixed models with the BAT-system's status as a fixed effect, day-time systolic blood pressure recordings from 24-hour ABP-measurements at baseline and after 8 months of follow-up were compared between individuals on BAT and continuous pharmacotherapy. Here, BAT-therapy was associated with a reduction in mean systolic day-time blood pressure of -11.7 mmHg (P < 0.0001). In conclusion, BAT-therapy may be a promising tool in lowering systolic blood pressure in individuals with refractory hypertension. Figure. Study design. ABPM = ambulatory blood pressure measurement. Device = Control of Device.