Uncontrolled and Resistant Hypertension
Hypertension is a leading risk factor for cardiovascular disease and a significant cause of morbidity and mortality. According to Frost & Sullivan, over one fourth of Chinese adults had hypertension as of 2019, and only approximately 22.0% of such patients had it under control (i.e., their blood pressure can be maintained below the treatment goal (average SBP below 140 mmHg and average DBP below 90 mmHg) relatively easily, with lifestyle changes and/or mild medications). On the other extreme, hypertension is considered resistant when the patient is taking at least three different types of antihypertensive medications (including diuretic) at their maximally tolerated doses, but the blood pressure still cannot be maintained below the 140/90 mmHg treatment goal. For hypertension cases which are more severe than controlled hypertension, but less severe than resistant hypertension, they are referred to as uncontrolled hypertension.
Treatment Solutions for Hypertension
According to Frost & Sullivan, the annual worldwide medical expenditures in relation to the treatment of hypertension amounted to approximately US$400 billion in 2019, which number is expected to further increase in the near future. Currently, there are three major treatment methods for hypertension, including lifestyle intervention (e.g., controlling weight, limiting salt intake and alcohol intake, increasing physical activities, reducing mental stress, etc.), pharmacotherapy, and interventional therapies (e.g., radiofrequency ablation of renal sympathetic nerves (renal denervation).
Adopting healthier lifestyles is always recommended, but lifestyle changes alone are difficult to treat uncontrolled or resistant hypertension. Pharmacotherapy alone is difficult to treat resistant hypertension, and even though it is effective in treating uncontrolled hypertension, pharmacotherapy requires uncontrolled hypertension patients to take a large amount of medications, at short intervals, for a very long term, and patients need to visit hospitals frequently for further check-ups and medication prescriptions. Many patients, especially young patients, often find such disruption to their daily lives unappealing, or even unacceptable. Antihypertensive drugs also have side effects (including diarrhea, dizziness, constipation, nausea, skin rash and weight loss, among others) and may interference with other medications. For example, thiazide diuretics may cause or worsen diabetes, beta blockers can worsen asthma and heart failure, and patients who are pregnant or planning a pregnancy may not be suitable for pharmacotherapy as they are subject to various restrictions on medication intake. As a result, hypertension patients’adherence to pharmacotherapy had been poor. According to Frost & Sullivan, approximately half of uncontrolled or resistant hypertension patients stopped taking their medications as prescribed by the physicians within one year of starting them, and approximately 20% of uncontrolled or resistant hypertension patients barely even tried to adhere to their physicians’pharmacotherapy prescriptions in the first place. Therefore, there exist unmet medical needs for effective, long-term alternative therapies, and the RDN therapy is gaining increasing attention as a promising therapy that has blockbuster potential to redefine the treatment paradigm for hypertension.
Renal Denervation Therapy
Blood pressure is controlled by a complex interaction of signaling from several systems within the body, including the nervous system, circulatory system, and endocrine (hormonal) systems. The nerves running to and from the kidney are especially important in the control of blood pressure. The excessive activation of the sympathetic nervous system in the kidney can lead to inappropriate activation of the renin-angiotensin-aldosterone system (RAAS), thereby causing enhanced vasoconstriction, abnormal sodium handling by the kidney, and increased blood volume, which may result in elevated blood pressure. In addition, excessive activation of the sympathetic nervous system may also affect the heart, causing increased cardiac output, which may also result in elevated blood pressure. Renal denervation (RDN) is a minimally invasive procedure that uses radiofrequency or ultrasonic ablation to destroy the nerves in the renal arteries without damaging the arteries. The process causes a reduction in the nerve activity, which helps decrease blood pressure.