Hypertension is a major global public health issue, posing significant health threats.
Hypertension is a fundamental disease worldwide, with a large patient population.
Globally, hypertension is a worldwide disease. The “Comprehensive Analysis Report on Global Hypertension Trends” co-authored by Imperial College London and the World Health Organization summarizes the prevalence of hypertension worldwide, providing a comprehensive overview of global hypertension trends. Over the thirty years from 1990 to 2019, age-standardized prevalence did not change significantly, but the number of hypertensive patients aged 30–79 nearly doubled, from 650 million to 1.28 billion cases.[1].
Hypertension is one of the common chronic diseases in China. According to the “China Cardiovascular Health and Disease Report 2021,” the number of hypertensive adults in China has reached 245 million.[2]. At the same time, with China’s future economic development, aging population, and accelerating urbanization, the number of hypertensive patients will continue to increase. Although hypertension is relatively easy to diagnose, the current treatment situation for hypertension in China is not ideal. In January 2023, the British Medical Journal (BMJ) published a survey report on 155,049 cases in China. In 2018, 87.6% of hypertensive adults aged 18–69 in China had poor control of their condition. Additionally, the awareness rate, treatment rate, and control rate of hypertension were all at low levels, at 38.3%, 34.6%, and 12.0%, respectively.[3].
Hypertension has a high mortality rate clinically and is the main risk factor for cardiovascular diseases.
High mortality rates due to hypertension impose a heavy disease burden on individuals, families, and society, and particularly affect residents in low- and middle-income countries. In 2019, global disease burden studies estimated that approximately 10.85 million deaths worldwide were caused by hypertension, accounting for about 31% of all deaths. In China, 259.99 million deaths were attributed to hypertension, with an attribution mortality rate of 182.79 per 100,000 people.[4].
If hypertension is combined with dyslipidemia, the coexistence can accelerate the progression of atherosclerosis, significantly increasing the risk of cardiovascular diseases, leading to stroke, ischemic heart disease, hypertensive heart disease, and other conditions.[5].The “Chinese Hypertension Prevention and Treatment Guidelines (2018)” state that the benefits of antihypertensive treatment mainly come from blood pressure reduction itself. The primary goal of treating hypertension is to minimize the occurrence and death risks of cardiovascular complications through effective antihypertensive treatment.[6].Blood pressure reduction of 5–10 mmHg has a significant impact on the risk of cardiovascular events, reducing the risk of stroke by 40% and ischemic heart disease by 23%[7,8]. As a major public health issue, the prevention and treatment of hypertension is urgent, and its treatment protocols continue to be improved through clinical practice.
Figure: The relationship between blood pressure reduction treatment and improvement in cardiovascular disease outcomes
Source: Literature search[7,8], Frost & Sullivan analysis
After a century of exploration, hypertension treatment technologies have made significant progress
At the beginning of the 20th century, Papin and Ambard performed open surgical denervation of the kidney nerves on humans for the first time. In the 1940s and 1950s, surgeons began frequently using visceral nerve resection or thoracic lumbar sympathetic nerve resection to treat severe hypertension. Some patients showed significant blood pressure reduction after surgery, reducing by 50–60 mmHg when lying down and up to 80–100 mmHg when standing. A long-term observational study of approximately 1,500 patients conducted by Peet in 1947 showed that about 80% of patients had a significant decrease in blood pressure, with improved symptoms after blood pressure returned to normal, and a significant reduction in the one-year mortality rate for malignant hypertension[9]In 1953, Smithwick and Reginald found that long-term follow-up studies of 1,266 patients showed significant improvements in mortality and survival rates, with about 45% of patients experiencing a significant decrease in blood pressure within 5 years[10]However, this invasive surgical method is complex to perform, causes significant trauma leading to high perioperative mortality rates, and involves various complications such as intestinal and bladder dysfunction, postural hypotension (systolic blood pressure <90 mmHg), and sexual dysfunction, making further research and application difficult[11,12].
Since the 1950s, blood pressure medications have been widely used in clinical practice and proven effective. Today, drug therapy remains the primary approach for hypertension, with many options available to patients. Common first-line drugs include diuretics, calcium channel blockers, beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor antagonists. However, globally, only about 20% of patients receive treatment and achieve target blood pressure levels[13]Poor blood pressure control can be attributed to lack of adherence to regular medication intake, intolerance to blood pressure medications, and fluctuations in drug concentration. Epidemiological studies show that 10% of all hypertensive patients have refractory hypertension (RH)[14]These patients, excluding secondary hypertension, cannot reach target blood pressure levels even after complete compliance with blood pressure treatment
Traditional therapies struggle to meet clinical needs, and there is an urgent need for effective, safe, and minimally invasive non-pharmaceutical blood pressure reduction methods. Although surgical approaches have gradually lost their advantages and were eventually abandoned, initial clinical evidence has confirmed the effectiveness of renal sympathetic nerve resection in blood pressure control. With the rapid development of minimally invasive vascular interventional techniques, surgical denervation treatments have been transformed into transcatheter renal denervation (RDN).Modern treatment goals aim to avoid various side effects associated with surgery through minimally invasive ablation, while also achieving long-term and continuous blood pressure reduction benefits, thereby surpassing the efficacy of drug therapy.
Image: The Evolution of Hypertension Treatment
Source: Public information, Frost & Sullivan analysis
The application prospects of RDN interventional therapy are broad, ushering in a new era in hypertension clinical treatment
The evidence-based path of RDN did not proceed as expected and encountered obstacles
With further research and clinical applications, the emerging therapy RDN has gradually transitioned from a preliminary concept to practical use in cardiovascular medicine. The clinical study using Medtronic’s Symplicity radiofrequency catheter was conducted first. Initially, Symplicity HTN-1 and HTN-2 small-scale trials showed positive results, indicating that RDN had good blood pressure reduction effects and safety[15,16]. This sparked a research boom in the industry, and the publication of these study results marked the beginning of RDN treatment for hypertension.
However, the multi-center, blinded, randomized controlled trial Symplicity HTN-3, published in 2014, showed that although RDN did not cause significant safety issues in treating refractory hypertension, its blood pressure reduction effect was not better than drug therapy[17]. This negative result led to significant controversy over the effectiveness of RDN therapy. As a result, Medtronic suspended the Symplicity HTN-4 trial and its clinical studies in India and Japan.
Rebuilding confidence through reason and moving forward based on historical experience
However, researchers believe that the results do not directly deny the effectiveness of RDN technology. After systematic analysis of basic scientific design, ablation strategies, and trial designs, several factors may have caused the trial to fall short of expectations, resulting in incomplete ablation, such as insufficient number of ablation points due to single-electrode technology, limited ablation to main vessels without branches, lack of monitoring of medication adherence, improper patient selection and surgical procedures, and lack of experience by surgeons[18].
Over the following years, the industry gained a deeper understanding of RDN, with multiple trials conducted. Among them, the important study Spyral HTN trial aimed to change the conclusions of Symplicity HTN-3. In 2015, Medtronic used the second-generation Spyral™ system, a improved four-electrode spiral radiofrequency catheter, and adjusted the trial design. A new SPYRAL HTN MED clinical trial program was launched, including SPYRAL HTN-ON MED and SPYRAL HTN-OFF MED. Both clinical trial results showed positive outcomes, and neither study reported any safety events related to RDN[19,20].
GSR (Global SYMPLICITY Registry) is the largest global RDN prospective, single-arm, global, observational, real-world registration study, involving over 3,000 patients with poor blood pressure control. In 2021, EuroPCR reported GSR findings, indicating that RDN using the Symplicity system had long-term effectiveness. Blood pressure decreased significantly by approximately 16.7 mmHg in each patient group, and the blood pressure reduction effect lasted for 3 years post-treatment, independent of antihypertensive drugs
Additionally, long-term follow-up results in Asia also demonstrate its effectiveness. In terms of safety data, no adverse safety events related to RDN devices or procedures were observed.[21]. The clinical scenarios in the real world are complex and variable, and the GSR study further confirms the clinical benefits of RDN. With the accumulation of evidence, hope emerges in the industry.
Looking back, the setbacks of SYMPLICITY HTN-3 did not mean the end of RDN technology; instead, it led to rational reflection—re-examining catheter RDN from catheter design, ablation strategies, to clinical trial designs. These valuable experiences promoted the optimization and iteration of RDN technology, and also increased industry attention to regulatory controls in clinical trials. Subsequent products equipped with advanced ablation devices, well-designed studies, and rigorously conducted clinical trials were introduced. Between 2020 and 2021, the U.S. Food and Drug Administration (FDA) recognized the RDN products of Medtronic, ReCor Medical, Sonivies, and Mavilai as “breakthrough devices”. Currently, research findings on sympathectomy are accumulating, forming a force for breakthrough.
Figure: Key randomized sham surgery-controlled RDN study results
Source: Literature[22], Frost & Sullivan analysis
The theoretical basis of RDN treatment—the close relationship between the renal sympathetic nervous system and the occurrence and maintenance of hypertension
The mechanism of hypertension is complex. Existing pathophysiological studies show that activation of the renal sympathetic nervous system plays an important role in the development of hypertension. The renal sympathetic nerves can be divided into afferent and efferent nerves. Activation of the renal sympathetic efferent nerves causes vasoconstriction of the renal arteries and activation of the renin-angiotensin-aldosterone system, leading to elevated blood pressure.
On the other hand, activation of the renal afferent nerves can increase hypothalamic systemic sympathetic activity and hormone release, resulting in increased vascular resistance and blood pressure. The principle of RDN treatment for hypertension is to block the efferent and afferent sympathetic pathways, reducing sympathetic activity in the kidneys and throughout the body, thereby preventing elevated blood pressure.[23].
Figure: Schematic diagram of the renal sympathetic afferent and efferent systems
Source: Publicly available information[24], Frost & Sullivan analysis
RDN, with its significant application advantages, is breaking through the limitations of traditional treatment methods
Over the past decade or so, non-pharmaceutical antihypertensive devices based on devices have emerged, and various efforts have been made to develop minimally invasive devices that achieve long-term blood pressure reduction through a single treatment. RDN therapy can effectively improve the achievement rate of hypertension targets, delay the progression of target organ damage, and enhance the quality of life of patients. Compared with surgical sympathectomy and visceral nerve resection, it has less trauma, shorter operation time and recovery time, no systemic adverse effects, and is more acceptable to patients.
Although drug combination treatment regimens are being optimized, patients still need to take medication regularly over a long period. RDN for blood pressure reduction breaks the long-standing problem of patients relying on drugs, overcoming medication adherence issues, and the blood pressure reduction has a 24-hour pattern, meaning the reduction is stable, solving the problem of blood pressure fluctuations within 24 hours due to peak and valley effects of drug blood levels.
By comparing the results of two ten-year follow-up studies, it is found that for patients with refractory hypertension, the therapeutic effect of medications diminishes after 10 years, leading to increased blood pressure, while RDN remains effective after 10 years. Additionally, RDN can reduce patients’ dependence on antihypertensive medications, with the average number of medications used by patients undergoing RDN reduced from 4.9 before surgery to 4.5[25,26]。
Figure: Comparison of long-term efficacy of drug therapy and RDN intervention
Source: Literature search[25,26], Frost & Sullivan analysis
The latest international position paper strongly recommends the clinical use of RDN
Several years ago, clinical experts were skeptical and cautious about RDN. However, with more data available, multiple expert consensus statements clearly support RDN in treating hypertension
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In 2021, the Society for Cardiovascular Angiography and Interventions (SCAI) and the National Kidney Foundation (NKF) issued a consensus statement on RDN applications, affirming its effectiveness and safety[27]。 -
In 2021, the European Society of Hypertension (ESH) guidelines on RDN indicate that RDN has good tolerability and lasting blood pressure reduction, and can serve as an alternative or additional treatment strategy for hypertension[28]。 -
In 2020, the Asian Consensus Statement on RDN states that when blood pressure targets are difficult to achieve and maintain, RDN can be used alone or in combination with medication therapy. Individuals at higher risk of cardiovascular disease should consider RDN[29]。
On February 15, 2023, ESC/EAPCI jointly published a consensus document on RDN for hypertension in the European Heart Journal. This consensus provides a more positive outlook on the clinical application of RDN. It reviews the evidence-based evidence of its effectiveness and safety in previous studies. Regarding indications, RDN intervention is no longer solely a treatment option for uncontrolled refractory hypertension, and the target population expands to patients with poorly controlled hypertension. Additionally, it is a good treatment option for patients who cannot tolerate long-term antihypertensive medications and have low compliance[22]。
Image: Categories of patients recommended for RDN surgery
Source: Publicly available information[22], Frost & Sullivan analysis
Various surgical approaches demonstrate their strengths, with radiofrequency RDN technology dominating the market
From a technological perspective, RDN ablation techniques are becoming more diverse
The ablation methods covered by RDN ablation technology include radiofrequency ablation, ultrasound ablation, chemical ablation, and cryoablation. Among these, radiofrequency ablation and ultrasound ablation are the mainstream technologies currently used. Ultrasound ablation uses high-frequency ultrasound to deliver energy for ablation, offering high penetration and wide coverage. However, it requires overcoming significant technical barriers, including high-frequency ultrasound transducers and high-power ultrasound output. Catheter-based radiofrequency ablation has been used in electrophysiology for over 20 years and is also the first ablation technique applied in the RDN field. With extensive clinical data and basic scientific research theories, radiofrequency ablation has seen rapid clinical progress and significant application advantages, potentially becoming the first technology category to enter the commercialization stage in the RDN field.
Radiofrequency RDN precisely detects impedance and controls temperature to selectively damage nerve fibers and reduce their activity
Sympathetic nerve fibers are densely distributed around the renal artery and extend into the adventitia of the renal artery. 90% of sympathetic nerves are within 6.39 mm of the vascular lumen. Animal experiments have shown that the median depth of injury from radiofrequency ablation of the renal artery is 6.53 mm[30]Therefore, most renal sympathetic nerves fall within the range of catheter-based radiofrequency ablation energy, which is the anatomical basis for successful transcatheter RDN treatment.
Radiofrequency ablation technology uses high-frequency alternating current to cause ions in surrounding tissues to oscillate at high frequencies and generate heat through friction, leading to tissue coagulative necrosis. The sympathetic nerves around the renal artery are complex and densely distributed. Compared to surrounding tissues, due to the lower resistance of nerve fibers, current flows more easily, resulting in higher current density within the nerve tissue and more energy being absorbed, raising the temperature above that of surrounding tissues.
Since the temperature threshold for nerve fiber damage is lower than that of vascular endothelium and smooth muscle, during radiofrequency RDN ablation, nerve fibers are more likely to be thermally damaged compared to vascular endothelium and middle layer smooth muscle. Additionally, appropriate temperature ensures that the vascular endothelium of the renal artery is not damaged, preventing serious adverse effects such as structural changes or narrowing of the renal artery.
Furthermore, a large number of sympathetic nerve fibers are located distal to the renal aorta and its branch vessels[31]Thus, the ablation range should not be limited to the main trunk but also cover the distal part of the renal aorta, branch arteries, and accessory renal arteries that can be ablated to achieve better ablation results.
In practice, the RDN device can be positioned along the percutaneous vascular path, such as the femoral or radial artery, to advance the catheter to the target ablation site. Then, based on real-time feedback from temperature and impedance sensors at the tip of the ablation catheter, the output power of radiofrequency energy is intelligently set. The radiofrequency energy penetrates the inner and middle layers of the renal artery and effectively reaches the sympathetic nerve fibers in the adventitia, causing them to become inactive. This effectively ablates the postganglionic fibers while preserving the sympathetic ganglion, thereby suppressing excessive sympathetic activation and achieving blood pressure reduction.
Radiofrequency RDN technology leverages innovation as its key advantage, driving rapid industry development
There are multiple challenges and limitations in the research and development of radiofrequency RDN, and further exploration is needed in areas such as device design and ablation strategies
The RDN clinical study results show that the proportion of patients responding to RDN using various energy sources ranges from 67% to 75%, yet many patients still do not achieve satisfactory responses.[32]It can be seen that the treatment response rate of RDN needs to be improved through device improvements and adjustment of ablation strategies, which also indicates possible design flaws in the inclusion criteria.
Currently, due to limitations in product design, the blood pressure reduction achieved by RDN devices based on published clinical trials is mostly within the range of 6–10 mmHg, with no significant advantage over common first-line antihypertensive drugs. However, the mechanism of action of RDN is neuroendocrine reregulation, not limited to the control of a specific drug site. The ultimate effectiveness of RDN therapy should aim to exceed traditional drug efficacy, similar to the blood pressure reduction achieved by surgical sympathetic ganglion resection, in order to realize the true clinical value of RDN therapy.[33].
Will "sensing" renal nerves be a future direction? Its feasibility remains to be verified in the future.
If sensing of renal nerves can be achieved, by identifying the targets of RDN ablation and determining the end points of ablation, RDN technology will become more precise, and the clinical treatment efficiency of RDN will increase. However, there is no strong evidence to support the feasibility of sensing RDN ablation in practice.
Firstly, classical physiology currently believes that the kidney is only controlled by the sympathetic nerve.[34]Secondly, considering the dense distribution of peripheral fibers in the renal artery, energy types such as radiofrequency energy, ultrasound energy, and cryo-energy cannot selectively ablate a single tissue or nerve type. Additionally, studies suggest that continuous activation of the renal sympathetic nerve can cause cardiac sympathetic activation, increasing the risk of ventricular arrhythmias.[35].
The method of high-frequency stimulation of the renal sympathetic nerve to sense RDN ablation remains unknown regarding the increase in cardiac sympathetic ganglion activity and the risk of ventricular arrhythmias, and further exploration is needed. At present, safe and effective ways to sense renal sympathetic nerve excitation may still rely on traditional methods such as complex radioactive tracers.
Key product design and standardized development elements are emerging.
Based on the anatomical structure of the renal artery, the research concept for achieving good blood pressure reduction and safety has gradually gained consensus in the industry:
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The design of ablation electrodes must conform to the spiral ablation characteristics of the renal artery. -
Accurate measurement and control of temperature, power, and impedance, with intelligent and automated output of appropriate ablation power. -
Good and stable contact between the ablation electrode and tissue ensures effective electrode attachment. -
Emphasis on continuous energy field generation to provide stable energy release for effective and comprehensive ablation. -
Intelligent RDN system ensures surgical standardization and effectiveness, reducing the learning curve for doctors.
To achieve an ablation range similar to surgical removal of ganglia while preserving sympathetic ganglia, and to avoid side effects such as orthostatic hypotension, in addition to catheter performance, factors such as the distance from the catheter to the renal artery, the depth of radiofrequency energy reaching the sympathetic nerves, the number of renal artery ablations, the area of renal artery ablation, and the degree of nerve damage all affect actual treatment outcomes. During RDN, renal aorta and its branches should be selected for combined ablation; as many effective ablation sites as possible should be chosen; based on the ablation sites, ablation energy and duration should be adjusted to reduce adverse reactions.
The research and development philosophy has been continuously improved, and radiofrequency RDN is innovating and optimizing along the technical path of “points – lines – surfaces – whole body”.
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"Points" represent the starting point of technology.
The first-generation RDN representative product is Medtronic’s Symplicity Flex. In catheter design, the concept from cardiac electrophysiology ablation products is adopted, using a single-point ablation head electrode design. The single-electrode ablation catheter is a “point contact” design. Although it can ablate the renal sympathetic nerve, due to poor adhesion and unstable attachment to blood vessels, it is easily disturbed by vascular vasomotor activity and respiratory movements, leading to incomplete ablation.
Due to the low level of surgical standardization in the first generation, it required high operational skills from surgeons, with manual parameter input. The operation mainly relied on doctors to judge the surgical process, resulting in long operation times and low ablation efficiency. Thus, it has been phased out by the industry.
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Transforming points into lines for more consistent “linear adhesion”.
The second-generation RDN technology’s representative product is Medtronic’s optimized Symplicity Spyral. To address the issues of limited electrode numbers and low ablation efficiency in the first generation, the second-generation RDN catheter has more electrodes and smaller electrode diameters. Using a multi-electrode catheter with smaller diameter allows combined ablation of renal aorta and branch arteries, thus increasing the blood pressure reduction effect.
Additionally, by adopting a spiral catheter design and introducing the concept of “linear adhesion”, due to design flaws, the spiral structure lacks compliance in tortuous main or branch blood vessels, making ablation difficult across them. In smaller blood vessels, the spiral structure elongates, increasing electrode dispersion, resulting in discontinuous ablation energy fields. In larger blood vessels, although the spiral structure can remain stable, electrode attachment is insufficient.
Furthermore, the second-generation product includes some intelligent features, such as temperature and impedance detection to assist doctors in judgment and operation, but there is still a lack of real-time power monitoring, preventing complete quantitative-efficiency feedback and intelligent logic.
Figure: Diagram of Medtronic Symplicity Spyral™ catheter.
Source: Company official website.
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Weaving surfaces into a network to form a “whole body”.
Although the second-generation product has made many improvements, several companies in the industry continue to invest heavily in overcoming technical barriers and creating better, lean device designs to achieve comprehensive ablation sites, good adhesion compatibility, and intelligent ablation. Based on deep understanding of product development and solid technical expertise, Meilizhuiye introduces the “surface adhesion” concept in the design of the third-generation RDN ablation catheter, using a net-basket electrode design and further expanding the number of electrodes.
The net surface composed of net-baskets provides sufficient three-dimensional support, and the six spirally distributed electrodes ensure good adhesion to the inner wall of blood vessels, ensuring continuous energy field operation for stable and effective “whole body” ablation. The net-baskets start in a retracted state and expand actively through an external handle button upon entering the blood vessel.
Due to the minimal axial dispersion between electrodes and significant radial deformation in web-like electrodes at various levels, it can adapt to different vascular shapes in complex three-dimensional spaces. It has a wide range of compatible vessel diameters, ranging from 3mm to 12mm. Based on good conformability, it can reach branch vessels through tortuous blood vessels, achieving ablation of a broader area.
In terms of device design, the six electrodes of the third-generation product are connected in parallel and arranged in a spiral pattern, each having an independent pathway. Each energy pathway can independently measure time, power, temperature, and impedance, enabling real-time control operations. Intelligent RF energy loading ensures precise ablation, effectively and completely destroying the sympathetic nerves along the pathway, aiming to achieve the maximum reduction in blood pressure through sympathectomy. In operation, temperature and impedance provide real-time feedback on adhesion and ablation effects, preventing doctors from relying on experience, thereby improving surgical efficiency.
Figure: Miliwei Web-like 6-Electrode Structure
Source: Company Official Website
Participants in the RF RDN field are advancing together to promote clinical research and market launch of RDN.
The vast application potential of RDN attracts global medical giants such as Medtronic, Abbott, and Boston Scientific. Academic papers, patents, and clinical trial progress demonstrate that China is at the forefront in RDN. In the development of RF RDN, companies like Miliwei, Baisinian, and Xinmai are among the domestic developers.
Miliwei:RDN Ablation System Netrod®In 2019, it received special approval for innovative medical devices from the state, obtained CE certification in 2020, and was recognized as a "Breakthrough Device" by the US FDA in 2021. In December 2022, the company completed the enrollment of all patients in RDN clinical trials and the data review, and is applying for product registration with the National Medical Products Administration (NMPA), aiming to become the first approved minimally invasive hypertension treatment device in China.
Baisinian:Second Generation Iberis®The multi-electrode renal artery RF ablation catheter system features a spiral 4-electrode structure, similar in appearance to Medtronic’s Symplicity Spyral™. The tip of the ablation catheter uses nickel-titanium alloy, which can automatically return to a spiral shape. On January 26, 2022, the company announced that the second generation Iberis®Clinical trial patient enrollment process.
Xinmai Medical:Renal Artery Mapping RF Ablation Catheter and accompanying mapping RF ablation instrument SyMapCath®™ /SymPioneer®™uses a single-electrode design to explore methods of selectively removing renal sympathetic nerves. In February 2022, the company announced that all patients were enrolled in the clinical trial (SMART Study).
Minimed Electrophysiology:FlashPoint™ Renal Artery Radiofrequency Ablation System passed the National Medical Products Administration (CFDA) review in 2017 and entered the special approval process for innovative medical devices. As of March 2023, it is still in the animal testing stage.
Image: Main product technology roadmap of RDN
Source: Public information, Frost & Sullivan analysis
The setting for effectiveness evaluation is a key focus in clinical trials and will also serve as the scientific foundation for the commercial development of RDN products in the future. First, as stated in the ESC/EAPCI clinical consensus on RDN treatment for adult hypertension, when no RDN product has been approved, the clinical trial design for RDN devices should undergo an equivalence test compared to drug therapy, that is, to verify that RDN treatment is superior to drug therapy. In the long term, once products are approved for market release, subsequent "head-to-head" non-equivalence trial designs will be conducted based on large sample sizes and strict non-inferiority thresholds to evaluate the safety and effectiveness of the products.[22].
Furthermore, there is extensive research and evidence supporting the correlation between blood pressure reduction and key clinical outcome events such as hypertensive target organ damage, cardiovascular complications, and overall mortality risk, as well as the ability to predict these clinical outcomes. The clinical efficacy of RDN should naturally be reflected in the hard indicator of blood pressure reduction.
On December 5, 2018, the U.S. Food and Drug Administration (FDA) held a panel meeting on circulatory system devices and provided recommendations for the effectiveness endpoint design in RDN clinical trials. Direct blood pressure reduction benefits are the main clinical indicator of whether RDN achieves effective ablation. The panel based on previous critical clinical trials and recommendations from Devices and Radiological Health (CDRH)[36]should use direct blood pressure reduction as the main efficacy endpoint to evaluate the new RDN blood pressure reduction devices. At present, composite clinical indicators such as win ratio and reduced drug load may be clinically significant, but due to the lack of evidence supporting their clinical significance, they are not the best hard endpoints for RDN blood pressure reduction effectiveness and can be used as secondary efficacy indicators for further in-depth exploration.
Leading companies in the RDN field still need to continue optimizing product design and structure to improve product performance and quality and achieve high ablation efficiency. Aiming at the blood pressure reduction level that surgery can achieve, that is, a reduction of 40-60 mmHg in systolic blood pressure at rest. The ultimate goal of RDN development is to increase the patient’s blood pressure compliance rate and bring more clinical benefits to patients.Based on this, the logic for judging clinical trial results in the future will extend from individual blood pressure reduction levels to group blood pressure reduction levels, then to the reduction in cardiovascular and cerebrovascular adverse events caused by elevated blood pressure, and ultimately to the reduction in overall mortality risk related to hypertension, as well as the extension of patient life expectancy.
Move forward, and look forward to the broad potential applications of RDN
With evidence-based medical evidence and high-quality devices, the safety and effectiveness of RDN technology are gradually recognized widely in clinical practice. RDN is no longer just a blood pressure reduction option for patients with stubborn hypertension. With its good tolerance and long-lasting blood pressure reduction effect, it may become a commonly used treatment method in the field of hypertension. In addition, in other disease areas characterized by increased sympathetic nerve activity, such as chronic kidney disease, heart failure, metabolic syndrome, and obstructive sleep apnea syndrome[37-41], RDN will also bring more treatment possibilities.
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