Catheter-Based Renal Denervation

Disruption of the renal sympathetic nerves via catheter-based radiofrequency ablation markedly reduces blood pressure levels in patients with refractory hypertension, according to findings from a proof-of-concept study (NCT00483808).

The renal sympathetic nerves play a key role in the progression of hypertensive disease. A new catheter-based system uses radiofrequency ablation to disrupt renal sympathetic nerves without affecting other abdominal, pelvic, or lower extremity nerves. In this trial, the renal denervation system was evaluated in 45 patients with a mean baseline blood pressure of 177/101 mm Hg and a mean heart rate of 72 bpm. Five additional patients enrolled but did not undergo ablation due to complicated anatomical features.

Henry Krum, PhD, Monash University and Alfred Hospital, Melbourne, Australia, presented findings from the trial, which were simultaneously published online in The Lancet.

Among treated patients, mean blood pressure fell by 14/10 mm Hg within 1 month of the ablation procedure (p<0.001) and dropped by 27/17 mm Hg after 1 year (p=0.02). By comparison, blood pressure levels increased among the 5 patients who were enrolled but did not receive renal denervation. After 1 year, the mean blood pressure rose by 26/17 mm Hg.

Physicians were instructed not to alter treatment unless medically required, and so most patients remained on their antihypertensive drug regimen throughout the follow-up period. Three patients required reduction of their medications after their blood pressures normalized. Nine patients had their medications increased, including 5 patients who had blood pressure reductions of at least 10 mm Hg and 4 who did not respond to the procedure.

No major complications were observed in either the renal artery or the kidney, and there was no apparent effect on renal function. The mean glomerular filtration rate (GFR) was 79 mL/min/1.73m² prior to the procedure and 83 mL/min/1.73m² 6 months following renal denervation.

Percutaneous renal sympathetic denervation represents a simple and effective approach to the management of hypertension in patients who are refractory to conventional pharmacologic therapy, Dr. Krum concluded. Future trials will define the long-term efficacy of renal denervation in resistant hypertension and other disorders, he said.

Activation of the Carotid Baroreflex

An implantable device that activates the baroreceptors of the carotid sinus significantly reduces blood pressure in patients with refractory hypertension, according to results from a small phase 2 feasibility study.

In hypertensive patients, blood pressure receptors within the carotid sinus do not detect elevated intravascular blood pressure, leading to an inadequate autonomic response. The Rheos^reg; hypertension system consists of a pulse generator, implanted near the collarbone, and carotid sinus leads. The device electrically stimulates the carotid sinus to activate blood pressure reflexes that lower heart rate, dilate blood vessels, and induce diuresis.

The phase 2 trial included 61 patients with systolic blood pressure ≥160 mm Hg who were resistant to 3 or more antihypertensive medications, including diuretics. After the Rheos device was surgically implanted and activated, blood pressure levels were measured at 1 year, 2 years, and 3 years. Marcos Rothstein, MD, Washington University School of Medicine, St. Louis, MO, presented findings in a late-breaking clinical trials session.

Mean blood pressure at baseline was 183/105 mm Hg despite treatment with a mean of 5.1 antihypertensive medications. On average, systolic blood pressure dropped by 25 mm Hg after 1 year, 22 mm Hg after 2 years, and 31 mm Hg after 3 years (p<0.001 at all time points). Diastolic blood pressure dropped by 15 mm Hg at 1 and 2 years and by 21 mm Hg by 3 years (p<0.001 at all time points).

Mean heart rate also fell by 7 bpm at 1 year (p<0.005), 8 bpm at 2 years (p<0.005), and 5 bpm at 3 years (p=0.15). Dr. Rothstein also observed a significant improvement in cardiac structure and function at 1 year, as measured by a decrease in left ventricular mass (p<0.05), left atrial dimension (p<0.05), and mitral A-wave velocity (p<0.05).

Based on promising early-phase results, the Rheos hypertension system is currently under evaluation in a phase 2 prospective, randomized, double-blind, placebo-controlled, multicenter trial with a target enrollment of 300 patients.