Hypertension Management

The disease

The World Health Organization has estimated that high blood pressure causes 1 in every 8 deaths worldwide, making hypertension the third leading killer in the world. ¹

A healthy blood pressure goal has a systolic reading below 140 mmHg, depending on the individual's health. Individuals who are unable to reach this goal, despite being on multiple blood pressure medications, are said to have “resistant hypertension". It is estimated that one in three people with high blood pressure has resistant hypertension.

When an individual has high blood pressure, small blood vessels can become damaged and less effective in supplying the body's vital organs (brain, heart and kidneys) with oxygen and nutrients. If an individual's systolic pressure is 160 mmHg, they face a four times greater risk of suffering a heart attack, stroke, or end stage kidney failure than an individual with normal blood pressure. ²

Autonomic imbalance plays a pivotal role in the etiology of hypertension. ³  Decreased parasympathetic and increased sympathetic tone increase peripheral vascular resistance, reduce renal blood flow, and increase sodium retention while impairing glucose handling and contributing to adverse cardiac and vascular remodelling.⁴

References:
1. The World Health Report 2012. World Health Organization; 2012:58. 2. Heart Disease and Stroke Statistics. American Heart Association, 2012 update. 3. Brook RD and Julius S. Autonomic imbalance, hypertension, and cardiovascular risk. Am J Hypertens (2000) 13 (S4): 112S-122S. 4. Bisognano JD et al. Baroreflex Activation Therapy Lowers Blood Pressure in Patients With Resistant Hypertension: Results From the Double-Blind, Randomized, Placebo-Controlled Rheos Pivotal Trial. JACC. 2011; 58: 7:765–773.

The need for better therapies

Polypharmacy and non-adherence make resistant hypertension a challenge ¹

Polypharmacy in resistant hypertension
Treated with 3 or more antihypertensive medications. ¹ The addition of a fourth or a fifth medication seldom provides any meaningful additional benefit.²

Managing comorbidities
The prevalence of chronic kidney disease or diabetes mellitus is higher in patients with resistant hypertension. ³ Co-morbidities can require additional medications.⁴

Multiple side effects
Up to 97% of patients who take antihypertensive medications experience drug side effects. ⁵

Non-adherence
Medication non-adherence * occurs in about 50% of newly treated hypertensive patients within the first year of treatment.⁵

Remain uncontrolled
Non-compliance increases the risk of uncontrolled hypertension about 5 times, as well as overall mortality, hospitalization rate and cost of care. ⁵

Increased risk of CV event
End-organ consequences include heart failure, stroke, ischemic heart disease and renal failure. ¹

In patients who remain above risk factor target despite treatment with multiple medications, the benefit of intensifying treatment is unclear. ²

* taking <80% of the number of prescribed pills

References:
1. Yaxley JP and Thambar SV. Resistant hypertension: an approach to management in primary care. J Family Med Prim Care. 2015 Apr-Jun; 4(2): 193–199. 2. Timbie JW et al. Diminishing Efficacy of Combination Therapy, Response-Heterogeneity, and Treatment Intolerance Limit the Attainability of Tight Risk Factor Control in Patients with Diabetes. Health Serv Res. 2010 Apr; 45(2): 437-456. 3. Bisognano JD et al. Baroreflex Activation Therapy Lowers Blood Pressure in Patients With Resistant Hypertension: Results From the Double-Blind, Randomized, Placebo-Controlled Rheos Pivotal Trial. JACC. 2011; 58: 7:765–773. 4. Long AN et al. The Comorbidities of Diabetes and Hypertension: Mechanisms and Approach to Target Organ Protection. J Clin Hypertens (Greenwich). 2011 April ; 13(4): 244–251. 5. Tedla YG and Bautista LE. Drug Side Effect Symptoms and Adherence to Antihypertensive Medication, Am J Hypertens. 2015 Dec 7. pii: hpv185. [Epub ahead of print].

The mechanism of action

The human body has its own mechanisms for sensing changes in blood pressure and other blood flow changes. This natural system is largely located in the brain, as well as the walls of the carotid arteries, which are the vessels in the neck that supply blood to the brain. Pressure sensors, called baroreceptors, are found on the carotid artery and in the carotid sinus. These sensors measure and report blood flow to the brain, which compares it to the body's needs.

BAROSTIM THERAPY™ is a neuromodulation therapy that activates the baroreceptors, which triggers the body's main cardiovascular reflex, to regulate blood pressure. ^1,2

By activating the baroreceptors in the wall of the carotid artery, BAROSTIM NEO™ is able to stimulate the afferent and efferent pathways of the autonomic nervous system. The brain responds by modulating efferent pathways, which relaxes the blood vessels, slows the heart rate and reduces fluid in the body. These actions reduce the afterload on the heart by decreasing arterial resistance, which can improve the heart's ability to pump blood to the tissues. The increase in parasympathetic tone and decrease in sympathetic drive results in the restoration of autonomic balance, which reduces excessive blood pressure and improves cardiac structure and function.

BAROSTIM THERAPY™ is the only treatment with the potential to reduce sympathetic activity while restoring parasympathetic activity. ³

References: 
1. Korner PI. Essential hypertension and its causes: neural and nonneural mechanisms. Oxford: Oxford University Press; 2007. 2. Gronda E et al. Baroreflex Activation Therapy: A New Approach to the Management of Advanced Heart Failure with Reduced Ejection Fraction. 2016; (under submission). 3. BAROSTIM NEO™ system reference guide. Available here – Last accessed March 2016

Demonstrated mechanism of action

BAROSTIM THERAPY™ is designed to reduce muscle sympathetic nerve activity. ⁵ Muscle sympathetic nerve activity (MSNA) falls and rises in tandem with blood pressure as BAROSTIM THERAPY™ is turned ON and OFF.⁵

MSNA after chronic therapy in a 68-year old female:

BAROSTIM THERAPY™ is designed to increase parasympathetic activity and decrease sympathetic activity. Chronic baroreceptor stimulation causes sustained changes in heart rate variability and heart rate turbulence that are consistent with inhibition of sympathetic activity and increase of parasympathetic activity in patients with drug-resistant systemic hypertension.

The key benefits

BAROSTIM THERAPY™ may offer resistant hypertension patients the ability to lower their cardiovascular risk by significantly lowering blood pressure. 

BAROSTIM THERAPY™ may reduce blood pressure, helping the majority of patients reach their systolic blood pressure goal. ¹* It is a neuromodulation therapy that triggers the body's main cardiovascular reflex to regulate blood pressure. 

BAROSTIM THERAPY™ showed a significant reduction in blood pressure and heart rate in a randomized controlled trial with the first generation device and was corroborated in a 30-patient study with BAROSTIM NEO™. ^1,2

Average responder reductions of 35 mmHg at month 12.¹

Proportion of patients achieving SBP of  ≤ 140 mmHg at month 6 and 12.¹

* Over half (55%) of patients in the pivotal trial achieved goal SBP of ≤140 mmHg

References: 
1. Bisognano JD et al. Baroreflex Activation Therapy Lowers Blood Pressure in Patients With Resistant Hypertension: Results From the Double-Blind, Randomized, Placebo-Controlled Rheos Pivotal Trial. JACC. 2011; 58: 7:765–773. 2. Hoppe UC, Brandt MC, Wachter R, Beige J, Rump LC, Kroon AA, Cates AW, Lovett EG, Haller H. 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. 2012;6(4):270-276.

In summary

* average of procedure time of 108 +/- 5 minutes

Humanitarian Device Exemption (HDE) Approval

The BAROSTIM NEO ^® LEGACY System has received Humanitarian Device Exemption (HDE) status from the Food and Drug Administration (FDA).  This means that in the United States The BAROSTIM NEO^® LEGACY System is a Humanitarian Use Device (HUD), or, “a device that is intended to benefit patients by treating or diagnosing a disease or condition that affects or is manifested in fewer than 4,000 individuals in the United States per year".¹

Patients who qualify to receive a BAROSTIM NEO ^® LEGACY System must meet all of the following criteria:

• Have resistant hypertension
• Have had bilateral implantation of the Rheos^® Carotid Sinus Leads Models 1010R, 1010L, 1014L, and 1014R (which have been discontinued and are obsolete)
• Have been identified as responders in the Rheos^® pivotal clinical study
• If a patient meets the above criteria, the device is considered as approved by FDA.

Use of the Carotid Sinus Lead Repair Kit is contraindicated in patients with infection at or near the implant pocket region.

CAUTION:
Federal law restricts this device to sale by or on the order of a physician.
Humanitarian Device. Authorized by Federal law for use in the treatment of resistant hypertensive patients implanted with the Rheos CSL leads. The effectiveness of this device has not been demonstrated. 

For more information on Humanitarian Device Exemption, please see here.

For more information on the BAROSTIM NEO ^® LEGACY System as a Humanitarian Device Exemption, including labeling and complete safety information, please see here.

References
1.  FDA.gov