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Professor Jiao Liqun: Ten years of CASSISS, our regrets and gains

Xuanwu Hospital Neurosurgery 2022-08-11 20:30 Posted in Beijing

The following article is from Stroke Vision, author Jiao Liqun


CASSISS has finally been published, and I am really very happy, because this is not only the presentation of an article in a top journal, but more importantly, it represents the efforts of our neuro intervention generation, or even two generations. Looking back at the development of the past ten years, it is full of regrets and harvests, but no matter which one is, it is worthy of our joy, because it represents growth.

From the beginning of the project, it is a "grass stage team" to put it bluntly. It was 2012, when the National Twelfth Five-Year Science and Technology Support Plan was declared. With the full support of Director Ling Feng, we received the support of the Ministry of Science and Technology. I, who have not had much experience in clinical trials, brought a few people who were equally ignorant. Four such clinical studies were initiated:

l  RECAS Study (National CEA and CAS Registry Study)

l  CRTICAS Study (National Register of Stenting Treatment of Intracranial Arterial Stenosis)

l  The CASSISS Study (Multicenter Randomized Controlled Study of Intracranial Arterial Stenting vs Drug Therapy)

l  CMOSS Study (Multicenter Randomized Controlled Study of Intracranial Arterial Bypass vs Drug Therapy)

Even now, this is a very big project, but at that time, it seemed that there was no fear at all. It just felt that we should do it, so we did it. Looking back, the experimental design was not perfect, the research funding was seriously insufficient, and the management Experience is not much better than blank, and it lacks the "research paradigm" that we are familiar with now. These are the "regrets" that we have been reflecting on ourselves over the past ten years, but the most rewarding thing for us is "courage". This is what we still hope to persist.


(Looking at the yearbook of that year, I am really grateful for our persistence and courage at that time, and of course, I was not too bloated at that time.)

Growing up

Courage alone is definitely not enough for science. During the 12th Five-Year Plan and the follow-up period, we have indeed encountered unprecedented difficulties. The most significant is the personnel and capabilities. At that time, the neurosurgery and neurointerventional circles did not have the design of prospective clinical studies, let alone large sample sizes and randomized controlled studies.

Just a few days ago, Director Shi Huaizhang was still telling me that at that time we really couldn't. If we do a new study now, it will definitely be more perfect. This is the true portrayal of ten years ago. Even the doctors in charge of us are also "indifferent" to clinical research. The person in charge does not take the initiative, resulting in some research lags and even missing data, because we do not have any specialized researchers. It's just that these doctors are working part-time, so naturally they will leave such regrets. But it is during the management and promotion of the experiment that all of us have received scientific education and promotion. This is an unavoidable growth process. If there is any regret, it is also an unavoidable price of growth.

Ten years have passed, and the growth depends on the help of teachers and friends and the collaborative efforts within the team. I still remember that after the successful application, in the face of such great pressure, Director Wang Daming told me that if we don’t do it, who will do it? As long as it feels right, let's do it together. To this day, these teams have maintained close cooperation. In ten years, what have we accomplished together?

1. RECAS research - coordinated by Chen Yanfei, Jiao Liqun and Hong Bo as PIs, 36 centers participated, 2719 cases;

2. CRTICAS research - coordinated by Wang Yabing, Jiao Liqun and Shi Huaizhang as PIs, 26 centers participated, 1140 cases;

3. CASSISS study - coordinated by Gao Peng, Jiao Liqun and Wang Daming as PIs, 8 centers participated, 380 cases;

4. CMOSS research - coordinated by Ma Yan, Ma Yan and Gu Yuxiang as PIs, 15 centers participated, 330 cases.

These are not what the Xuanwu Dan Center can undertake, nor what Xuanwu led everyone to complete, but the trust, support and help of many domestic brothers and teams to complete the answer sheet together. Here, I sincerely thank these teachers and friends, not for the sake of one Articles or research, but for the common contribution and growth of this decade.


(The ten years we have witnessed are not a few papers or a few studies, but the scientific development of cerebrovascular surgery and intervention in China.)


In addition to the team who worked together, I would also like to thank many scholars for their help:

Professor Caplan, as a senior at the senior level, when he was 80 years old, he also had a telephone conference with us for more than two hours for the details of the CASSISS research, and he still provided many pertinent opinions before the publication;

A few years ago, Professor Williams Powers made a special trip to China from Raleigh, the United States, and spent the whole afternoon analyzing the two studies of CASSISS and CMOSS for our team. Although this is the first time to China, he is familiar with our experiments. even stronger than ourselves;

Prof. Timo Krings, Prof. Adnan Qureshi, Prof. Osama O Zaidat, Prof. Nobuyuki SAKAI have been giving us a lot of guidance in the design, management and monitoring of the trial;

Prof. David S Liebeskind, Prof. Colin P. Derdeyn, Prof. Adam A. Dmytriw played a huge role in the conception and structure adjustment of the article;

There are also Professor Liao Hanwen, Professor Yu Junhao and Professor Huang Haohui from Hong Kong, Macao and Taiwan. Due to the innate closeness of thinking and language, we not only can easily obtain their help, but also deepen friendship and cooperation through research.

We would also like to thank our statistical cooperation team, Prof. Wu Yangfeng and Prof. Wang Haibo from Peking University, for giving us a real insight into the "ceiling" level of data processing, analysis and interpretation;

I also want to thank Stryker, Mr. Wang Jian, Ms. Zhao Song and Ernest. A truly responsible company is not about selling products, but helping the industry develop in the right direction;

Thanks to Tigermed for undertaking the data work, and to Ms. Li Caihong for her contributions to our team's clinical research over the past ten years.

Finally, I would like to thank Professor Jiang Weijian, who has played an important leading role in this field, who first started the prospective design of intracranial artery stenosis and brought Chinese research to the level of Neurology and Stroke;

Thanks to Director Miao Zhongrong, who not only led the team to maturity, but also completed the single-center randomized controlled study of intracranial stent very early;

I would also like to thank Professor Liu Jianmin, Professor Liu Xinfeng, Professor Yang Qingwu, etc. It was you who made the top international journals recognize the work of Chinese doctors in neurological intervention, and also made a good preparation for the following researchers. Yesterday's JAMA was published once. Two studies from China, and congratulations to Professor Yang Qingwu's team.


(Thanks to the help of these experts and professors, the scientific development of neurointervention in China needs more international perspectives.)


After we agreed to talk about regrets and gains, why did the painting style suddenly turn into an "award acceptance speech"?

Speaking of regrets, perhaps the biggest “regret” for neurointerventional physicians who have been following the CASSISS study is this “bland” result.

Once upon a time, we swore that a clinical trial would confirm the status of intracranial artery stents, thereby changing recommendations for clinical practice, but CASSISS did not conclude that stents were superior to medical therapy, and the 30-day rate of stroke or death was 5.1 in the stent group. % in the drug group and 2.2% in the drug group; there was no significant difference in the composite endpoint during 1-year follow-up (8.0% in the stent group vs 7.2% in the drug group); nor was there a difference in the rate of stroke in the responsible vessel area at 2 years (9.9% in the stent group vs 9.0 in the drug group). %); there was also no difference in the 3-year cumulative composite endpoint (14.2% in the stent group vs 18.0% in the drug group). Is this a "negative result" conclusion? What does this mean for us trying to change clinical practice?


Is this another end to interventional therapy for intracranial artery stenosis?

We must face up to the point that the effect of drug therapy for intracranial artery stenosis is relatively stable to a certain extent. From the SAMMPRIS study in 2012 to today's CASSISS, many studies have confirmed this. In this context , interventional therapy must control complications to be low enough to obtain additional benefits.

But on the other hand, is the composite endpoint of 18% at 3 years of drug therapy acceptable? It may be okay as a statistic, but for doctors and patients, this number should be infinitely lower, which is why we are constantly trying more aggressive treatments.

Once upon a time, CEA couldn't show an advantage over drugs, CAS was far worse than CEA, and intra-arterial thrombectomy was inferior to IV thrombectomy, but now? In the process of medical development, we will see an interesting phenomenon. When the treatment of diseases is not ideal, surgical techniques will emerge as the times require, and gradually become slightly better than drug treatment until a new drug is born. The competition has risen to another level, because surgery/intervention has a good prognosis, depending on surgical indications, perioperative management, surgical instruments and techniques, which are likely to be more mature in a shorter period of time compared to the cycle of drug development Yes, the competition between the two treatment methods is actually the reason why the disease treatment is getting better and better.

Going back to intracranial artery stenosis, interventional complications have gradually decreased over the past decade. Although CASSISS cannot prove that intracranial stents are superior to drug therapy, they have been proven to be non-inferior to drug therapy, and they have begun to show advantages in long-term prognosis (although still There is no statistical difference), which makes me firmly believe that it is still a rising period for the interventional treatment of intracranial artery stenosis. If you are not the kind of doctor who sticks to the rules and is satisfied with the figure of 18%, please be based on standardized training. Joining the team of interventional therapy, because in the face of diseases, the concept that doctors uphold is not limited to any method, but insists on development and a more positive treatment attitude.


(Compared with two studies from a decade ago, CASSISS achieved better results for both drug and stent options.)

What is the future of intracranial artery stenosis?

Although the publication of CASSISS in JAMA is a very honorable thing, I always believe that there is nothing special about this kind of confirmatory research, because scientifically, this is not a new discovery, but a new discovery at this stage. The summary of the phenomenon, how to see the essence through the phenomenon, is the true meaning of this research.

From the point of view of CASSISS, current drug treatment cannot avoid adverse outcomes in all patients, and stents can also avoid adverse outcomes in most patients. The patient is more suitable for drug or interventional therapy.

Therefore, maybe the two methods are not contradictory, but complementary. What CASSISS really tells you is not which method is better, but to remind you that we do not understand the disease of intracranial arterial stenosis, and the current standard is probably It is difficult to distinguish which patients with intracranial artery stenosis are at high risk. What we really need is to classify similar intracranial artery stenosis into different types and different risk stratification by means of precision medicine, so as to be able to target them. Choosing a treatment method will be the "spring" of interventional therapy, and it will also be the "spring" of drug treatment.

During the 13th Five-Year Plan period, our CASSISS team has done some preliminary work, and it will still be our key research direction in the future.


(From simple narrow measure of evolution to precise evaluation of structure and function.)

What does a "negative" clinical study mean? Is it a failure?

I still remember seeing an interesting article published by NEJM a few years ago - "The Primary Outcome Fails - What Next?", which roughly means to reflect on the flaws of the experiment, dig into other meanings of the data, and seek external evidence This is what we will do now. On the day we received JAMA, we decided to start the CASSISS-FU (Follow Up) study group with three purposes:

First, strengthen the in-depth analysis of data and increase long-term follow-up for up to 5 years and 10 years;

Second, strengthen data exchange with other similar studies, and discover new conclusions through scientific methods;

Third, the research group will open the desensitized data as a public dataset to more researchers one year after the results are published. Because this is an original research supported by the state, it should serve more doctors and patients, so CASSISS will take the lead, hoping that more clinical research will be done in this way, in order to build a big data system of diseases in the Chinese population.

I believe that CASSISS-FU will have new research content to present, but the most important thing is that young doctors will make their debut as the main force. In ten years, a better group of doctors has been cultivated, and they deserve more from you. expect.


Write at the end

I still want to thank "Director Ling", who is Director Ling Feng's far-sighted vision. In 2000, he established the first cerebral ischemia revascularization team in China, and trained a large number of professional doctors for the country; The "harsh" requirements of "a clinician who can do research, an internist who can hold a scalpel and a catheter" force us to keep moving forward; it was also her who laid out this "big drama" ten years ago. With today's results from CASSISS.


Thanks to the participating hospitals and all members of the CASSISS research group, we would like to introduce ourselves:

Member of the CASSISS study group


Finally, I would like to thank our Xuanwu internal team for their support. President Zhao Guoguang and Director Zhang Hongqi have given us the best working environment in the past ten years, and the full degree of freedom has inspired a stronger sense of responsibility;

Thanks to our small team - Zhu Fengshui, Ma Yan, Wang Yabing, Chen Yanfei, Chen Jian, Yang Bin, Chen Fei, Lu Xia;


Thanks to Dr. Gao Peng and Dr. Wang Tao for their hard work in the CASSISS study, as well as the input of many young doctors;

Thanks to our families, behind the ten years of hard work is your hard work;

Finally, thanks to our patients, it is your needs that support our continuous progress.

Cast ten years, the last sword.

We have reason to be proud, because CASSISS is the original research of Chinese neurointerventional doctors after ten years, which represents the trouble and joy of our growth; we have more reason to look forward to it, because CASSISS is only the tip of the iceberg of many Chinese studies, and the future of China, There must be better development.

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