The latest combined data from European and US phase 2 clinical trials with an implantable device being developed to treat patients with drug-refractory hypertension were reported at the Innovation in Intervention: i2 Summit 2007, held as a subset of, and in conjunction with, the 2007 American College of Cardiology (ACC) meeting and cosponsored by the Society for Cardiovascular Angiography and Interventions. Presenter Peter W. de Leeuw, MD, PhD (University Hospital Maastricht, The Netherlands) said that the investigators are pleased with the early clinical results to date and are optimistic about this novel treatment approach.
Refractory or resistant hypertension is usually defined as blood pressure that remains above goal (140/90 mm Hg in most patients or 130/80 mm Hg in those with diabetes or renal disease or systolic blood pressure (SBP) > 160 mm Hg in patients with isolated systolic hypertension) despite adherence to an appropriate 3-drug regimen including a diuretic.[2,3] Estimates of the prevalence of truly resistant hypertension vary from 5% to 40% of the treated hypertensive population. Without further options, these patients are at high risk for myocardial infarction (MI), stroke, and heart and kidney failure.
The Rheos Baroreflex Hypertension Therapy (BHT) system (CVRx; Minneapolis, Minnesota) provides a "physiologic rationale" method to reduce blood pressure. The system's proprietary technology uses the body's own natural blood pressure regulation system (baroreflex) to control blood pressure. The Rheos BHT system includes:
A small pulse generator that is implanted under the collarbone;
Two thin lead wires that are implanted at the left and right carotid arteries and which connect to the pulse generator; and
The Rheos Programmer system, an external device used by physicians to noninvasively regulate the activation energy from the generator to the lead wires.
The system electronically activates the baroreflex, which sends signals to the brain that are interpreted by the brain as suggesting a blood pressure increase. The brain then acts to lower blood pressure by signaling various neural control systems in the body to reduce blood pressure, including the blood vessels, heart, and kidneys.
Study Parameters and Results
Prof de Leeuw presented an analysis of combined data from 27 patients (17 European and 10 US) participating in the US Rheos Feasibility Trial and the European Device Based Therapy of Hypertension Trial (DEBuT-HT). These data were presented separately in 2006.[6,7] [See ESH 2006 and AHA 2006 Medscape reports.] All of the patients (14 men and 13 women, mean age 52 years) had stage 2 hypertension (≥ 160 mm Hg) despite taking 3 or more antihypertensive medications, including a diuretic.
The Rheos BHT was surgically implanted in these patients and was then activated 1 month later. All subjects remained on antihypertensive therapy during the study. One patient developed an infection before 3 months and was excluded from the analysis. After 6 months of active Rheos BHT treatment, SBP in the remaining patients was significantly reduced by an average of 21 mm Hg (166 vs 187 mm Hg, P = .007) and diastolic blood pressure (DBP) was significantly reduced by an average of 16 mm Hg (96 vs 112 mm Hg, P = .0004) ( Table ). Heart rate was also reduced significantly by 9 bpm (72 vs 81 bpm, P = .013). The Rheos BHT system continues to be effective in controlling blood pressure even after 1 year, Prof de Leeuw reported.
To date (March 1, 2007), 49 patients have been implanted with the Rheos BHT system worldwide, providing 822 patient-months of follow-up. The implants have been well tolerated, with no unexpected serious adverse events. There have been no reports of postural hypertension associated with the device, there is no evidence of stenosis of the carotid artery out to 1 year, and there have been no lead or pulse generator failures. Twelve system- or procedure-related adverse events have been reported in 10 subjects. Most of these were resolved and did not lead to the patient's exclusion from the study.
Prof de Leeuw believes that the Rheos BHT treatment approach could offer a new option for patients with drug-resistant hypertension, saying that "It may prevent progression to more serious illnesses and death." A larger study has begun to further assess long-term benefit of the system. In October 2006, CVRx received conditional investigational device exemption (IDE) approval from the Food and Drug Administration (FDA) to begin a US pivotal clinical trial that is evaluating the safety and effectiveness of Rheos BHT in a much larger number of patients.
The Rheos Pivotal Trial is a prospective, blinded, randomized clinical trial that will be conducted in 300 patients at up to 50 medical sites. To be enrolled in the trial, patients need to be resistant to treatment with 3 or more antihypertension agents, including a diuretic, and their SBP must be ≥ 160 mm Hg. Prior to randomization, patients will have their device turned off for 1 month following the implant. After 1 month, patients will be randomized at a 2:1 ratio to Rheos BHT "on" or "off" for the first 6 months. After 6 months, all patients will receive active therapy. At the end of 12 months, patients in the "on" group who are considered to be responders -- defined as a ≥ 10 mm Hg reduction in office cuff SBP -- will be assessed for sustained response. Patients will then be followed on a quarterly basis until study closure. Results from this study are intended to support the Pre-Market Approval (PMA) application for the Rheos BHT system to the FDA.
Findings from 2 preclinical studies that evaluated the Rheos BHT system in canine subjects with heart failure were also presented at the ACC meeting. In both studies, Rheos BHT was found to improve left ventricular function.[8,9]
Medscape Cardiology © 2007 Medscape
Cite this: Chronic Treatment of Resistant Hypertension With the Rheos Baroreflex Hypertension Therapy System - Medscape - Jun 12, 2007.