The collection and collection of high-value medical consumables in the mainland has accelerated, and the pacemaker has become a "veteran" of collection and procurement.
On September 8, 2021, the "3+ N" procurement alliance in the Beijing-Tianjin-Hebei region (13 provinces such as Beijing-Tianjin-Hebei Heijiliao, Mengjin, Lu, Yuchuan, Qianzang and other provinces) carried out the linkage procurement of coronary drug balloons and pacemakers, of which Shandong only participated in balloon procurement, and Beijing, Shanxi, Henan and Guizhou only participated in pacemaker procurement.
Subsequently, on October 18, 2021, Shaanxi Province, together with gansu, Ningxia, Xinjiang, Xinjiang Construction Corps, Hunan, Guangxi, Hainan and other interprovincial alliances, issued a procurement plan to carry out double-chamber pacemaker procurement.
Among them, in the full-body compatible MRI (magnetic resonance imaging) double-chamber pacemaker, Boston Scientific, Abbott, Medtronic, More than 100 Force to be selected, Medtronic quoted the lowest price of 18871.62 yuan, Abbott quoted the highest price of 19879.27 yuan; in the non-compatible MRI pacemaker, Chuangling Heart Rhythm, Lepu Medicine, Boston Science, Abbott, Medtronic proposed to be selected, Lepu Medicine reported the lowest price of 12895.96 yuan, Medtronic quoted the highest price of 18190.29 yuan.
Pacemaker gathering events across the continent
As early as 2019, the pacemaker field has appeared in the collection of figures. As a major province for pacemaker implantation in mainland China, Jiangsu Province took the lead in the collection of dual-chamber pacemakers in 2019. The first collection was moderate, with an average decrease of about 15.86%. In May 2021, Jiangsu Province launched the second collection of dual-chamber pacemakers, with an average reduction of up to 60%, and the average price of full-body MRI-compatible double-chamber pacemakers with an average price of 60,000 yuan was reduced to about 20,000 yuan.
It can be seen from the past collection events that the continental pacemaker collection has always been in a relatively mild state. However, the second collection of jiangsu province and the collection of inter-provincial alliances are strengthening.
In the case of accelerated collection, pacemaker products themselves have two major barriers - 1, high technical threshold, competitive innovative products bargaining space, such as 2020 Shandong Province centralized procurement of pacemakers, there are experts on remote monitoring, MRI compatible double-cavity pacemaker products and enterprises to negotiate prices, 13 products average price reduction of 16.86%, the maximum reduction of 31.78%; 2, pacemaker products with a strong long-term service nature, the price includes management fees, maintenance costs, Pacemaker manufacturers need to support engineers, and if the price decline is too severe, it may "scare away" some overseas companies.
Therefore, pacemakers are unlikely to have the same major price reduction as coronary stents, but the compression of profit margins is still a major problem.
Treatment of bradycardia,
Dual-chamber pacemakers are the most common
Pacemakers are undoubtedly a dark horse of the twenty-first century.
In 1984, the American Association of Professional Engineers listed the pacemaker alongside semiconductors and lasers as the top ten most outstanding inventions of the first half of the century. In 2001, the Internet and pacemaker won the highest award for engineering in the United States. In April 2021, former U.S. Vice President Mike Pence underwent pacemaker surgery.
Pacemakers are mainly used to treat patients with bradycardia and are currently the most effective treatment. Bradycardia may be caused by dysfunction of the sinoatrial node (SA), atrioventricular node (AV), or other parts of the heart conduction system. Such patients have a decrease in heart output, insufficient blood supply to important organs and tissues, mild affect life, severe cases will faint or even sudden death.
With the development of cardiac pacing technology, the function of the pacemaker has also developed from a single treatment of bradyarrhythmias to the treatment of ECG disorders (atrial fibrillation, ventricular fibrillation, etc.) and non-ECG disorders (heart failure, etc.). CRT-P (Double Ventricular Pacemaker for Cardiac Resynchronization) corrects interventricular and intraventricular dissynchronism, thereby improving symptoms and improving survival in patients with heart failure.
Cardiac pacing is a combination of bioengineering, electronics and clinical treatment technology. A pacemaker consists of a pulse generator and electrode wires. Among them, the pulse generator is composed of an integrated circuit and a battery, and there are complex lines inside that control the pacemaker.< One end of the electrode wire is connected to the pacemaker, and the other end reaches the heart through a vein and is fixed to the myocardial wall by a special structure.
Electrical impulses generated by pulse generators are conducted to the heart through electrode wires, stimulating the contraction of the heart, thereby increasing the heart rate and alleviating the symptoms associated with bradycardia in patients.
Depending on the placement, pacemakers can be divided into in vitro temporary pacemakers and permanently implantable pacemakers. Clinically, there are two main cases in which an in vitro temporary pacemaker is used, one is that the patient has a previous bradyarrhythmia, and the pacemaker is implanted when anesthesia or surgery is needed to prevent various symptoms caused by too low heart rate; the other is before the patient implants a permanent pacemaker as a temporary transition.
According to the difference in the implantation site of the electrode wire, the pacemaker can be divided into a single-chamber pacemaker, a double-chamber pacemaker, a three-chamber pacemaker, and a four-chamber pacemaker, of which the single-chamber pacemaker can be divided into a VVI pacemaker (the top electrode of the electrode wire is placed at the muscle girder at the tip of the right ventricle) and an AAI pacemaker (the top electrode of the electrode wire is placed in the comb muscle of the right atrial appendage).
Since the implantation of the first pacemaker in 1958, about one million patients worldwide are currently being treated annually with pacing. According to the China Cardiovascular Health and Disease Report 2020, the number of patients implanted with pacemakers in mainland China in 2019 increased by 9.3% compared with 2018, and dual-chamber pacemakers accounted for nearly 70%. In terms of indications for pacemaker implantation, the proportion of pathological sinus node syndrome accounted for 50.08%, AV block accounted for 43.52%, and other pacemaker indications accounted for 6.4%.
Annual Implantation of Pacemakers in China Data Source: China Cardiovascular Health and Disease Report 2020
The incidence of arrhythmias is about the same in China and the United States, but the total population of China is much higher than that of the United States. However, 1,000 people per million people in the United States have a pacemaker implanted, compared with only 60 per million people in China.
The reasons for the low penetration rate of pacemakers in China are: 1, there are few doctors who master pacemaker implantation technology, and the pacemaker implantation surgery carried out in China is mainly concentrated in the top three hospitals in large cities; 2, the pacemaker price is high, and the single-cavity pacemaker is a low-end product, and the domestic price is 20,000 to 30,000 yuan. The most important product type in the domestic market of double-chamber pacemakers is priced at about 60,000 yuan in China. The three-chamber pacemaker is the most high-end product, the domestic price is about 100,000 yuan, and there is no domestic brand at present. At the same time, the subsequent replacement of electrode wires, management, and maintenance are all a large expense.
According to the current operation process of the mainland, the waste electrode wire is generally not removed, but the waste electrode wire is stored in the body with the newly implanted wire. The wire is generally considered to be pulled out after infection, and in most cases, the original electrode is cut off and embedded, and a new one is implanted. At the same time, the use time of the pacemaker is related to the patient's own physical condition, if the patient's heart rate is better, the pacing function is not commonly used, and the use time of the product may be longer.
Since Minimally Invasive, Lepu and Xianjian entered the pacemaker field, the mainland pacemaker market can enter the early stage of localization, and it has been swept by the collection hurricane, and the entire market cannot help but cast a shadow. Under the dilemma of high threshold, high monopoly and high investment, where will Chinese local enterprises go?
The global cardiovascular big four,
All three are developing pacemakers
The global cardiovascular four giants are Medtronic, Abbott, Boston Scientific, Edward Science, the first three are laying out the heart rhythm management track, occupying more than 80% of the mainland pacemaker market.
In 1958, Medtronic brought the world's first battery-powered pacemaker.
In 2016, Medtronic's Micra leadless pacemaker was approved by the FDA for use in patients requiring right ventricular pacing. Traditional pacemakers have a greater chance of infection due to the presence of wires and sacs. Micra wireless pacemakers have no electrode leads, no pocket bags, can be attached to the inner wall of the heart after implantation, the volume is only the size of a vitamin capsule, 93% less than traditional pacemakers, and the weight is only about 2 grams.
At the same time, the Micra wireless pacemaker is compatible with 1.5 T/3.0 T full body MRI scans and is equipped with Bluetooth capabilities. MRI is a common clinical imaging test, and with the aging of the population, the demand for MRI tests in patients with pacemaker implants in mainland China is gradually increasing. In 2019, Micra pacemakers were approved for marketing by NMPA.
A premarket clinical study of Medtronic Mira pacemakers, which included 726 patients in 56 centers, spent 2 years of study and observation, found that compared with traditional pacemakers, the leadless pacemaker reduced the incidence of major complications by 48%, and the immediate success rate of surgery reached 99.2%. Post-marketing clinical research data showed that compared with traditional transvenous (TV-VVI) pacemakers, Micra's re-intervention rate decreased by 38% after two years and chronic complications decreased by 31%.
Two large-scale clinical trials confirmed the advantages of a leadless pacemaker. But there is still an unsolved dilemma, that is, price. Since its approval in 2019, the Micra pacemaker has successfully carried out about 3,000 implants on the mainland.
Medtronic pacemaker products Data source: Medtronic official website
Traditional right ventricular pacing increases the incidence of heart failure and atrial fibrillation in patients, and reducing unnecessary ventricular pacing can reduce unnecessary atrial fibrillation. According to Medtronic's official website, the three major strategies of ventricular pacing are to encourage patients to conduct themselves, prevent out-of-sync, and restore synchronicity.
Abbott occupies 23.7% of the mainland market, and the company's Assurity is the world's smallest MRI-compatible pacemaker with a service life of up to 10 years, reducing the risk of infection and complications from changing pacemaker equipment.
At the same time, Assurity pacemaker implantation has the shortest time interval from when an MRI scan can be performed. According to Abbott's official website, IFU recommends that Medtronic, Boston Scientific, and Baitori products need to wait 42 days to do MRI scans, while Abbott's products do not need to wait, and can be immediately MRI scans without affecting the performance of the equipment.
In addition, Abbott's Aveir miniature wireless pacemakers are directly benchmarked against Medtronic Micra pacemakers and can be recovered if the system needs to be replaced or changed during the patient's treatment. The product caters for on-demand pacing with less energy required for pacing.
Abbott pacemaker products Data source: Abbott official website
The Boston Scientific ACCOLADE Series Pacemakers are a full line of pacemakers with the most MRI programmable options, compatible with 1.5T/3T MRI checks, and no limits on MRI scan time. At the same time, it has not yet applied to patient limits, and the service life of the equipment is up to 13 years.
The Edora 8 SR-T ProMRI pacemaker is a 10cc single-chamber pacemaker that has been in use for 13 years. MRI-compatible pacemakers are developing rapidly, but programming before and after examinations increases the burden on medical staff. The product has an MRI AutoDetect function, which automatically detects the MRI environment, converts to a safe MRI mode within 10 seconds, and within 1 minute of leaving the magnetic field area, the device will automatically call back to the original setting without additional programming. This not only simplifies the doctor's workflow, but also reduces the patient's time in MRI mode.
At the same time, the pacemaker has a closed-loop stimulation (CLS) function, which can be combined with the human autonomic nervous system to simulate normal sinus node function, and clinical trials have confirmed that CLS can respond according to different conditions and emotional changes in patients' daily activities, providing physiological support for patients.
The pacemaker has undergone an upgrade of "solid rate type - on-demand type - physiological type - automatic type". The pacing frequency of early pacemakers is fixed and is always an ectopic point for normal cardiac pacing in the human body. Today's pacemakers can simulate the normal activity of the human heart and perform physiological pacing.
In addition, the mainland took the lead in proposing Hip system pacing, including Hissian beam or left bundle branch pacing (LBBP), which has developed rapidly in China since 2017 and has gradually become the mainstream technology in the field of pacing. Hippo system pacing is a physiological pacing that preserves left ventricular contraction synchronization and maintains normal conduction of the patient's heart compared to traditional right ventricular pacing. At the same time, the left bundle branch pacing is close to physiological pacing, which makes up for part of the deficiency of Heath's bundle pacing, and has been actively carried out in the clinic.
Combing the pacemaker products of each head enterprise, it will be found that miniaturization, intelligence, full body MRI compatibility, reducing unnecessary ventricular pacing, and supporting remote follow-up are the focus of pacemaker development.
In August 2021, the European Society of Cardiology (ESC) published new guidelines based on the 2013 edition of the Guidelines for Cardiac Pacing and Cardiac Resynchronization. The guidelines recommend remote device management to reduce the number of follow-up visits to the office for difficult patients and to make Category IA recommendations. At the same time, the guidelines recommend that for patients implanted with MRI-compatible pacemakers, MRI tests can be performed according to the manufacturer's operating instructions and make Category IA recommendations.
In addition, innovative products are constantly emerging clinically. Researchers in the United States have developed the world's first in vivo degrading pacemaker, temporary, completely wireless, battery-free control, and can degrade harmlessly within 5-7 weeks. The pacemaker is made entirely of absorbable materials and is small in size, weighing only 0.3 grams. However, at present, absorbable pacemakers must be implanted through open chest surgery, which is more invasive.
Domestic pacemaker to achieve a breakthrough from 0 to 1,
Market domestic production rate is only 5%
The number of patients with arrhythmias in mainland China exceeds 10 million, and with the increasing aging of the mainland population, the incidence of arrhythmias is increasing year by year, and the market share of pacemakers and defibrillators is also increasing year by year. In 2020, the domestic pacemaker market size is about 4 billion yuan.
However, the mainland pacemaker market has long been monopolized by imported brands, according to the statistical analysis of Bohai Securities Research Institute, in 2018, Medtronic, Abbott (St. Jude), Baitoli, Boston Scientific pacemaker products accounted for nearly 95% of the mainland market, while minimally invasive medical, Lepu Medical, Anderson Technology only accounted for about 5% of the share.
Approved domestic pacemaker Data source: The official website of the State Drug Administration
In the field of pacemakers, the three head domestic companies are not old players and have taken different development paths.
■ Minimally invasive medical treatment
Weichuang took the lead in entering the market with the introduction and acquisition, and became the leader of domestic pacemakers. In 2014, MicroPort Medical and Solin (the predecessor of LivaNova) established a joint venture company Chuangling Heart Rhythm, and MicroPort Holdings 51%, obtained the exclusive sales right of Solin products in China, and began to independently develop domestic pacemakers. In September 2017, Chuangling Heart Rhythm's Rega series of implantable pacemakers was clinically approved by NMPA.
Rega pacemaker has a total of 8 models in 3 series of heart orchid, heart rhyme, heart joy, with automation, physiological, small volume of international functions and long life characteristics, its volume is only 8 cubic centimeters, the service life can reach 10-12 years. Among them, The Rega series of products can be used for 12 years, providing patients with a unique sleep apnea test to prevent cardiovascular diseases caused by sleep apnea and hypoventilation.
In 2018, MicroPort joined hands with Yunfeng Fund to acquire LivaNova's heart rhythm management business. Combined with technology imported from Solin, Italy, Tron Heart Rhythm produces a pacemaker with a volume of 8cc, making it the smallest pacemaker in the world. As of September 2021, the number of implants of Chuangling Heart Rhythm "Heart Series" pacemakers exceeded 10,000.
At the same time, Chuang ling heart rhythm has Bluetooth function and can be used with SmartView Connect home remote monitors Alizea, Borea and Celea pacemakers in 2020 to submit registration applications in Europe, the United States, Japan, and obtain CE certification in January 2021, which will accelerate its commercialization process.
In addition, Tronlink's Kora 100 pacemaker with extrathoracic MRI compatibility has submitted an application for registration. The ENO series pacemaker and Vega electrode wire have completed the type test, and the pre-market 1.5+3.0T whole-body MRI compatible clinical trial will be launched soon, and the domestic leadless pacemaker project has also been officially launched.
According to The 2020 annual report of MicroPort Group, the company's revenue in 2020 was 648.7 million US dollars, of which 27.8% came from its heart rhythm management business, achieving revenue of 180.3 million US dollars. The company's pacemaker business increased by 24.7% year-on-year in 2020, covering 168 hospitals, and by the end of 2020, it has entered 480 hospitals, continuing to maintain the market position of the first domestic pacemaker brand share. The company has achieved a growth rate of more than 50% in the implantation of domestic pacemakers for two consecutive years.
■ Xianjian Technology
LifeTech and Medtronic reached a strategic cooperation to jointly produce Pacemakers of the Lifetech brand for the Chinese market. Medtronic will provide specific technology, training and support to jointly commercialize pacemaker systems when Pioneer enters the Chinese pacemaker market.
With the help of the technology and resources of multinational giants, the heartTone series implantable pacemakers jointly developed by the two parties were approved by NMPA in December 2017. At the same time, the 8301 temporary pacemaker independently developed by Xianjian Technology was approved by the FDA and CE in 2019 and 2020 respectively.
LifeTech's Model 8301 Temporary Pacemaker, a pacing/analysis two-in-one multi-functional product, won the German Red Dot Design Award 2018. It provides single-cavity extracorporeal temporary pacing for patients with bradycardia, pacemaker and defibrillator implantation for pacing system analysis, and continuously displays intraluminal electrographs in real time. The product is the first domestic temporary pacemaker with completely independent intellectual property rights, and was approved by NMPA in April 2021.
At present, Xianjian Technology is still developing the 6108 temporary pacemaker, which uses the same pacing and sensing technology platform as the 8301 temporary pacemaker, but the volume is only 40% of the 8301 temporary pacemaker. In addition, in December 2021, Xianjian Technology and Medtronic further expanded the strategic cooperation of the "Xintong" pacemaker project, and the two sides will start the project cooperation of domestic MRI-compatible pacemaker systems. Medtronic will provide a range of technical consulting services for this MRI-compatible pacemaker program and waive royalties for the corresponding products under certain conditions.
According to The 2020 Annual Report of LifeTech, by the end of 2020, the pacing electrophysiology business (mainly related to pacemakers, including pacemakers and electrode wire products) contributed about 2.46 million yuan, an increase of about 11.8%. In 2020, the global epidemic is in the outbreak stage, and considering this part of the social factors, the growth rate of 11.8% is also gratifying.
According to the company's 2021 semi-annual report, as of the end of June 2021, the turnover of the pacing electrophysiology business was about 1.52 million yuan, an increase of about 508.0% over the same period in 2020.
■ Lepu Medical
Lepu Medical acquired Qin ming Medicine and established Lepu Medical Appliances. Lepu Medical is a typical case of relying on mergers and acquisitions to become bigger and stronger, and the company officially entered the pacemaker market after the acquisition of Qinming Medicine. Qin Ming Medicine is the earliest enterprise specializing in pacemaker business in China, and the single-chamber pacemaker developed by the company in cooperation with Xi'an Jiaotong University has successfully broken the import monopoly of the domestic market. The product is mainly for the low-end market, but the overall market share is low.
In October 2016, the Dual-Chamber Pacemakers Qinming8631D and Qinming8631DR were approved for listing, which is the first dual-chamber pacemaker with independent intellectual property rights and frequency response function in China. Up to now, only the dual-chamber pacemaker of Lepu Medical Appliances in domestic enterprises has been approved by NMPA.
At present, the company is developing an MRI-compatible fully automatic pacemaker, and the Qinming8632 fully automatic pacemaker is in clinical trials.
In addition to the three head enterprises, there are currently no other domestic companies whose pacemaker products have been approved or entered the approval process for innovative medical devices. Compared with overseas enterprises that have entered the domestic market in large quantities, local innovation in the mainland is relatively lacking. In the field of pacemakers with high technical thresholds, import monopolies, collection and procurement are accelerating, the living space of domestic enterprises seems to have begun to narrow, and the pacemaker market is "beating too slowly".
But this market is also showing new vitality, in addition to the domestic enterprises to develop MRI-compatible, wireless pacemaker, the relevant medical insurance adjustment will reduce the pacemaker implant patient self-payment amount - from December 1, 2021, Heze pacemaker to cancel the limit payment, according to the actual price as the base for settlement; from January 1, 2022, Zhenjiang City to implement the new policy of medical insurance special medical materials payment, insured patients personal expenditure will be reduced by more than 20%, the pacemaker's medical insurance limit price will be adjusted.
It can be seen that the collection of high-value consumables is on the road, and enterprises, governments, and clinics are also accelerating.
Resources:
Lepu Medical, Minimally Invasive Medical, Andystek 2020 Annual Report
"Pacemaker Collection: "Gentle Knife", Waist Cut is Wonderful" - Cai Jian Dao
"More expensive than coronary stents, can pacemakers reduce prices through national collections?" ------------------
China Cardiovascular Health and Disease Report 2020
*Cover image source: 123rf