|MP 8.01.57||Baroreflex Stimulation Devices|
|Original Policy Date
|Last Review Status/Date
Reviewed with literature search/8:2014
|Return to Medical Policy Index|
Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract. Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage. Medical technology is constantly changing, and we reserve the right to review and update our policies periodically.
The baroreceptors are pressure sensors contained within the walls of the carotid arteries. They are part of the autonomic nervous system that regulates basic physiologic functions such as heart rate and blood pressure (BP). When these receptors are stretched, as occurs with increases in blood pressure, the baroreflex is activated. Activation of the baroreflex sends signals to the brain, which responds by inhibiting sympathetic nervous system output and increasing parasympathetic nervous system output. The effect of this activation is to reduce heart rate and blood pressure, thereby helping to maintain homeostasis of the circulatory system.
Hypertension is a widely prevalent condition, which is estimated to affect approximately 30% of the population in the United States. (1) It accounts for a high burden of morbidity related to strokes, ischemic heart disease, kidney disease, and peripheral arterial disease. Resistant hypertension is defined as elevated blood pressure despite treatment with at least 3 antihypertensive agents at optimal doses. Resistant hypertension is a relatively common condition, given the large number of individuals with hypertension. In large clinical trials of hypertension treatment, up to 20-30% of participants meet the definition for resistant hypertension, and in tertiary care hypertension clinics, the prevalence has been estimated to be 11-18%. (1) Resistant hypertension is associated with a higher risk for adverse outcomes such as stroke, myocardial infarction (MI), heart failure, and kidney failure.
There are a number of factors that may contribute to uncontrolled hypertension, and these should be considered and addressed in all patients with hypertension prior to labeling a patient as resistant. These include non-adherence to medications, excessive salt intake, inadequate doses of medications, excess alcohol intake, volume overload, drug-induced hypertension, and other forms of secondary hypertension. (2) Also, sometimes it is necessary to address comorbid conditions, i.e., obstructive sleep apnea, in order to adequately control BP.
Treatment for resistant hypertension is mainly intensified drug therapy, sometimes with the use of non-traditional antihypertensive medications such as spironolactone and/or minoxidil. However, control of resistant hypertension with additional medications is often challenging and can lead to high costs and frequent adverse effects of treatment. As a result, there is a large unmet need for additional treatments that can control resistant hypertension. Non-pharmacologic interventions for resistant hypertension include modulation of the baroreflex receptor, and/or radiofrequency denervation of the renal nerves.
Baroreflex Stimulation Devices
Devices that activate the baroreflex are implantable devices that provide electrical stimulation to the baroreceptors. At least one company has developed devices for this purpose; no baroflex activation device has received approval or clearance from the U.S. Food and Drug Administration (FDA).
The Rheos® Hypertension system (CRVx™, Minneapolis, MN) consists of 3 components:
1) Implantable pulse generator, which controls and delivers the electrical energy. It is implanted subcutaneously beneath the collarbone by minimally invasive surgery.
2) Carotid sinus leads, which are thin wires with electrical contacts that are placed in contact with the carotid baroreceptors. They conduct the electrical energy from the pulse generator to the baroreceptors.
3) The programmer system, which is an external device that allows clinicians to turn the system on and off and regulate the electrical signal delivered to the baroreceptors.
CVRx™ has replaced the Rheos® system with a “second-generation” device called the Barostim neo™. The device consists of a unilateral electrode and lead that is attached to the carotid sinus and a pulse generator that is implanted subcutaneously in the chest wall. Programming is performed via radiofrequency telemetry using an external laptop computer and software.
There are no baroreflex activation therapy devices that have received U.S. FDA approval or clearance.
Use of baroreflex stimulation implanted devices is considered investigational.
BlueCard/National Account Issues
No applicable information.
This policy was created in August 2011 and updated periodically with literature review. The most recent update with literature review covers the period through June 25, 2014.
The literature review focused on identification of controlled trials, particularly randomized controlled trials (RCTs). RCTs are crucial in determining efficacy of this treatment due to the natural variability in blood pressure (BP), the heterogeneity of the patient populations with increased BP, and the presence of many potential confounders of outcome. Case series have limited utility for determining efficacy. They can be useful for demonstrating potential of the technique, determining the rate of short- and long-term adverse effects of treatment, and to evaluate the durability of the treatment response.
There was 1 published RCT evaluating baroflex stimulation for lowering blood pressure, the Rheos® pivotal trial.2 The trial, published in 2011, was double-blind and included patients with resistant hypertension defined as at least 1 systolic blood pressure (SBP) measurement of 160 mm Hg or more with diastolic BP 80 mm Hg or more after at least 1 month of maximally tolerated medical therapy. A total of 322 patients had the Rheos® system implanted, and 265 patients underwent randomization. Participants were randomized in a 2:1 fashion to the device turned on or off for a 6-month period. After 6 months, all patients had the device turned on. The primary efficacy end points were the percent of patients achieving at least 10 mm Hg decrease in SBP at the 6-month time point (acute efficacy) and the percent of patients who maintained their BP response over the 6 to 12 month time period (sustained efficacy). Primary safety outcomes were defined thresholds for procedural safety (at least 82% of patients free from procedural adverse events at 30 days), therapy safety (not more than 15% excess treatment-related adverse events in experimental group), and device safety (at least 72% of patients free from procedural or therapy-related adverse events at 12 months).
At 6 months, 54% of patients in the stimulation group had an SBP decrease of 10 mm Hg or more, compared with 46% of patients in the control group (p=0.97), indicating that the primary acute efficacy outcome was not met. The primary sustained efficacy outcome was met, with 88% of patients who responded at 6 months maintaining a response at 12 months. A secondary efficacy outcome, the percent of patients reaching target SBP, did show a significant group difference. A total of 42% of the patients in the active treatment group reached a target SBP of 140 mm Hg, compared with 24% in the control group (p=0.005). For the primary procedural safety end point, the predefined threshold of 82% was not met. At 30 days, the percent of patients free of procedural adverse events was 74.8%. The primary safety end point of therapy safety was met, with a similar percent of patients free of treatment-related adverse effects at 6 months (91.7% vs 89.3%, p<0.001 for noninferiority). The primary safety end point of device safety was also met, with 87.2% of patients free of device-related adverse events at 12 months, exceeding the predefined threshold of 72%.
Patients who actively participated in the Rheos® pivotal trial continued to be followed after 12 months, and additional data were reported in 2012 by Bakris et al.3 A total of 276 of the 322 implanted patients (86%) consented to long-term open-label follow-up. After a mean follow-up of 28 months, 244 of 276 (88%) were considered to be clinically significant responders. Response was defined as sustained achievement of the target SBP (≤140 mm Hg, or ≤130 mm Hg for patients with diabetes or renal disease) or a reduction in SBP of 20 mm Hg or more from device activation. Alternatively, patients could qualify as a responder if their implanted device was deactivated and if they had an increase in SBP of at least 20 mm Hg in the 30 days after device deactivation. In the extension study, there was no comparison group.
The DEBut-HT trial4 was a multicenter, single-arm feasibility study of the Rheos® BAT system published in 2010. This study enrolled 45 subjects, from 9 clinical centers in Europe, with resistant hypertension defined as a BP of greater than 160/90, despite treatment with at least 3 antihypertensive drugs, including a diuretic. The planned follow-up period was 3 months, with a smaller number of patients followed for up to 2 years. In 37 patients completing the 3-month protocol, systolic office BP was reduced by 21+4 mm Hg (p<0.001) and diastolic BP was reduced by 12±2 mm Hg (p<0.001). There was a smaller reduction in 24-hour ambulatory BP (n=26), with a decrease of 6±3 mm Hg in systolic BP (p=0.10) and a decrease of 4±2 mm Hg in diastolic BP (p=0.04). In 26 patients followed for 1 year, the declines in office BP were 30±6 mm Hg systolic (p<0.001) and 20±4 mm Hg diastolic (p<0.001). For ambulatory BP (n=15), the 1- year declines were 13±3 mm Hg systolic (p<0.001) and 8±2 mm Hg diastolic (p=0.001). A total of 7 of 42 patients (16.7%) experienced adverse events. Three patients required device removal due to infection; 1 patient experienced perioperative stroke; 1 patient experienced tongue paresis due to hypoglossal nerve injury; 1 patient had postoperative pulmonary edema; and 1 patient required reintervention for movement of the device.
Several other smaller feasibility studies have been reported. For example, Heusser et al5 treated 12 patients who had treatment-resistant hypertension with the Rheos® system. The mean baseline BP was 193/94 mm Hg, and at 1 month following implantation, there were decreases in SBP of 32±10 mm Hg (p=0.01). The decrease in diastolic BP was not reported. Tordoir et al(6) treated 21 patients with the Rheos® system and reported acute decreases in BP at 1 to 3 days postimplantation. The mean baseline BP was 189.6/110.7 mm Hg, with a reduction post-treatment of 28±22 mm Hg systolic, and 16±11 diastolic. Adverse events reported included infection necessitating removal (n=1), hypoglossal nerve injury (n=1), wound complications (n=3); intraoperative bradycardia (n=2); and pain (n=5).
In 2012, Hoppe et al published the results of a series of patients treated with the Barostim Neo™.(7) Thirty patients from 7 centers in Europe and Canada with resistant hypertension were treated with this device and followed for a 6-month period. The mean baseline BP was 172/100. At 6 months, there was a decrease in BP of 26.0 mm Hg systolic and 12.4 mm Hg diastolic. The percent of patients achieving adequate BP control, defined as a systolic BP of 140 or less, was 43%. There were 3 perioperative complications, 1 device pocket hematoma, 1 wound complication, and 1 intermittent pain at the insertion site. One additional patient had longer term intermittent pain at the device site.
Ongoing and Unpublished Clinical Trials
CVRx Barostim Hypertension Pivotal Trial (NCT01679132)(8): This RCT is evaluating the safety and efficacy of the Barostim Neo device in people with treatment-resistant hypertension. Resistant hypertension is defined as a SBP of at least 160 mm Hg, despite a stable regimen of 4 or more maximally tolerated antihypertensive medications. Patients will be randomized to receive optimal medical management alone or optimal medical management plus baroreflex stimulation. Primary outcomes are reduction in SBP at 6 months and adverse events. The expected enrollment is 310 patients and the estimated date of study completion is July 2015.
Barostim Hope for Heart Failure (HOPE4HF) Study (NCT01720160)(9): This RCT is evaluating the safety and efficacy of the Barostim Neo device in people with heart failure. Patients will be randomized to receive optimal medical management alone or optimal medical management plus baroreflex stimulation. Primary outcomes are improvements in heart failure metrics and system and procedure-related adverse events. The expected enrollment is 60 patients and the estimated date of study completion is January 2015.
Barostim Neo System in the Treatment of Heart Failure (NCT01471860)(10): This is an RCT comparing baroreflex stimulation with medical management in patients with symptomatic heart failure, despite a stable pharmacologic regimen. The primary outcome measure is change in left ventricular ejection fraction after 6 month follow-up. The planned enrollment is for 150 participants, with an estimated completion date of January 2015.
Summary of Evidence
The use of baroreflex stimulation devices is a potential alternative treatment for resistant hypertension. Specific devices for baroreflex stimulation have been developed, but none have received approval from the Food and Drug Administration (FDA) for any indication. Small, uncontrolled feasibility studies report short-term reductions in blood pressure (BP), together with adverse events such as infection, hypoglossal nerve injury, and wound complications. Results of a randomized controlled trial (RCT) comparing baroreflex stimulation with continued medical therapy were published in 2011. This trial met some efficacy end points but not others. There was not a significant increase in the percent of patients achieving at least a 10 mm Hg decrease in systolic blood pressure (SBP) at 6 months, but more patients in the treatment
group did reach a target SBP of 140 mm Hg or less at 6 months. The trial met 2 of 3 predefined safety end points. Further research from RCTs is needed to determine whether baroreflex activation therapy is effective in reducing BP for patients with resistant hypertension. Because of limited evidence showing benefit, and the lack of FDA approval, this treatment is considered investigational.
Practice Guidelines and Position Statements
No relevant guidelines or statements were identified.
U.S. Preventive Services Task Force Recommendations
Baroreflex activation therapy is not a preventive service.
Medicare National Coverage
There is no national coverage determination (NCD). In the absence of an NCD, coverage decisions are left to the discretion of local Medicare carriers.
- Acelajado MC, Calhoun DA. Resistant hypertension, secondary hypertension, and hypertensive crises:diagnostic evaluation and treatment. Cardiol Clin. Nov 2010;28(4):639-654. PMID 20937447
- Bisognano JD, Bakris G, Nadim MK, et al. Baroreflex activation therapy lowers blood pressure in patients with resistant hypertension results from the double-blind, randomized, placebo-controlled rheos pivotal trial. J Am Coll Cardiol. Aug 9 2011;58(7):765-773. PMID 21816315
- Bakris GL, Nadim MK, Haller H, et al. Baroreflex activation therapy provides durable benefit in patients with resistant hypertension: results of long-term follow-up in the Rheos Pivotal Trial. J Am Soc Hypertens. Mar-Apr 2012;6(2):152-158. PMID 22341199
- Scheffers IJ, Kroon AA, Schmidli J, et al. Novel baroreflex activation therapy in resistant hypertension: results of a European multi-center feasibility study. J Am Coll Cardiol. Oct 5 2010;56(15):1254-1258. PMID 20883933
- Heusser K, Tank J, Engeli S, et al. Carotid baroreceptor stimulation, sympathetic activity, baroreflex function, and blood pressure in hypertensive patients. Hypertension. Mar 2010;55(3):619-626. PMID 20101001
- Tordoir JH, Scheffers I, Schmidli J, et al. An implantable carotid sinus baroreflex activating system: surgical technique and short-term outcome from a multi-center feasibility trial for the treatment of resistant hypertension. Eur J Vasc Endovasc Surg. Apr 2007;33(4):414-421. PMID 17227715
- Hoppe UC, Brandt MC, Wachter R, et al. Minimally invasive system for baroreflex activation therapy chronically lowers blood pressure with pacemaker-like safety profile: results from the Barostim neo trial. J Am Soc Hypertens. Jun 11 2012;6(4):270-276. PMID 22694986
- Sponsored by CRVx Inc. CVRx Barostim Hypertension Pivotal Trial (NCT01679132). www.clinicaltrials.gov. Last accessed June, 2014.
- Sponsored by CRVx Inc. Barostim Hope for Heart Failure (HOPE4HF) Study (NCT01720160).
www.clinicaltrials.gov. Last accessed June, 2014.
- Sponsored by CRVx Inc. Barostim Neo System in the Treatment of Heart Failure (NCT01471860).
www.clinicaltrial.gov. Last accessed June, 2014.
|CPT||See Policy Guidelines|
|ICD-9-CM Diagnosis||Investigational for all diagnoses|
|ICD-9-CM Procedure||39.81-39.88||Implantation, replacement, revision, and removal code range for carotid sinus stimulation device|
|ICD-10-CM (effective 10/1/15)||Investigational for all diagnoses|
|ICD-10-PCS (effective 10/1/15)||03HK0MZ, 03HK3MZ, 03HK4MZ, 03HL0MZ, 03HL3MZ, 03HL4MZ||Surgical, upper arteries, insertion, stimulator lead code list (code by approach and body part)|
|0JH60MZ, 0JH63MZ||Surgical, subcutaneous tissue and fascia, chest, insertion, stimulator generator code list (code by approach)|
Baroreflex activation therapy
Carotid barorflex stimulation
|08/11/11||Add to Therapy section||new policy|
|08/09/12||Replace policy||Policy updated with literature review. Reference 7 added, no change to policy statement|
|8/08/13||Replace policy||Policy updated with literature review through July 2, 2013; references 4, 9 and 10 added, no change to policy statement.|
|8/14/14||replace policy||Policy updated with literature review through June 25, 2014. No change to policy statement.|