1. 026 门诊 CLINIC
东闻视野·国际瞭望 outlook
CLINIC & PCR Family: Approach to
PCR Experts Perspective
As we approach the half-year point of 2016, we CLINIC, a
leading provider of professional academic media, hope to see
unsurpassed, insurmountable progress in the cardiovascular field.
At the onset of the year, CLINIC began a strategic collaboration
with the PCR Family. This collaboration provides numerous
opportunities for us to conduct interviews with the European PCR
Faculties and to serve as a window into the cardiovascular field
in China. As part of this collaboration, we will report the current
advances of Chinese medicine to the European professionals and
the world. In addition, we will introduce the gains made in the
cardiovascular field in Europe to Chinese professionals.
During this year’s China Interventional Therapeutic Conference
(CIT Conference), CLINIC interacted with three outstanding
European PCR experts: Professor William Wijns (PCR Chairman
and Course Director of EuroPCR, Belgium), Professor Patrick
Serruys (Editor-in-chief of EuroIntervention, Netherland), and Dr.
Christoph Naber, the leader in TAVI technology (Course Director
of AsiaPCR, Germany). CLINIC conducted topic-based interviews
with each expert to gain insight on their perspective of their three
respective topics relevant to the most up to date information.
Within the past four years, ILUMIEN I and ILUMIEN II
both have been completed and reported and the ILUMIEN III
enrolment is completed. In his interview with CLINIC, Dr. Wijns
explained that intracoronary imaging, especially the respective
clinical value of OCT and IVUS, remains one of his favorite
topics to discuss and research. With the recent news of Artificial
Intelligence (AI) defeating the reigning champion of weiqi, the
concept and assumptions of AI have come into sharp focus in
the medical world. Dr. Naber provided his opinion on the recent
progress in the implementation of AI into the clinical strategy
making process and the possibility of AI replacing human brain
analysis. Naber felt it was an interesting and critical topic to
address. Lastly, Dr. Serruys provided insight on the unanimous
FDA decision to approve the use of Absorb bioresorbable
scaffold on March 16th 2016, which quickly became breaking
news in the medical community. Serruys, who was present to
testify to the FDA explaining the merits of the device, was the
primary investigator of several fundamental Absorb studies.
Serruys believes in the prospect of bioresorbable scaffold and his
commentary on the next goal of BRS in terms of technological
progress.
The three interviews will be presented in the next consecutive
two month issues of Clinic•Cardiology. Through CLINIC’s paper
media channel, CLINIC eliminates the distance between the two
continents, conveying the European PCR experts’ perspectives
to Chinese professionals in order to make an approachable cross-
continental interaction.
Editor: Yubing Jin Photographer: Hui Chen
4. 029门诊 CLINIC
PCR Expert Perspective:
Intracoronary Imaging
& PCR EducatioN
A. The Respective Value of OCT and IVUS
Clinic: OCT has limitations as compared to IVUS in
guiding complex PCI, such as, left main, ostial lesions,
dm>3.5 mm lesion including vein grafts, and severe
CKD and HF patients. The perspective is that OCT
is the complement of IVUS in these lesions. What is
the genuine or substantial limitation of OCT in those
subsets?
Dr. William Wijns: Thank you for asking about one of my
favorite topics – intracoronary imaging and the respective clinical
value of OCT and IVUS. You listed a number of anatomic or
clinical situations where IVUS may be preferable to OCT; for
instance ostial lesions, very large vessels, or patients in whom
one cannot inject a lot of contrast. However, largely, the imaging
resolution of OCT is superior to IVUS. It is much easier for
physicians to read an OCT image than to understand an IVUS
image. To truly understand the IVUS image, you must be an
expert – expert in IVUS will most likely be able to retrieve the
same level of information as what is provided by OCT. The only
missing link with OCT is the capacity to look at vessel remodeling
be it constrictive or expansive. IVUS is superior to OCT in depth
Dr. William Wijns
Background of Interview
The Series of ILUMIEN trials focused on OCT guidance
as compared to IVUS guidance. ILUMIEN I and
ILUMIEN II both have been completed and reported.
The ILUMIEN III enrolment is completed.
5. 030 门诊 CLINIC
东闻视野·国际瞭望 outlook
imaging penetration. Otherwise, I feel that the detailed imaging
resolution of OCT is superior.
In my opinion, the real question is not whether OCT or IVUS is
better; the question at hand, instead, is whether invasive imaging
provides superior outcomes. As we know, IVUS has been around
for a longer time. As such, we have more data showing that IVUS
can be useful in improving certain procedural techniques and in
certain subsets of patients, for example, left main PCI. On the
other hand, similar data are being accumulated progressively
for OCT. At this time, we do not have a specific set of studies
for OCT in this regard. However, there are a number of very
interesting studies that compare the performance of OCT versus
the performance of IVUS. This is important particularly for Asia
and the US, where imaging is more accepted and used more
frequently than in Europe. In Europe, physicians have a hard time
convincing the payer to reimburse intracoronary imaging and to
provide the necessary funding to allow us to perform PCI under
imaging guidance.
Clinic: It seems that between OCT and IVUS, each
has its respective advantages and shortcomings. Is it
possible that OCT can surpass IVUS? If so, how will
this be accomplished?
Dr. William Wijns: Yes, the strength of OCT is the detailed
definition of the images. The fact that we have now good
opportunities to co-register OCT with angiography allows us to
know exactly which part of the artery we are viewing. The same
co-registration softwares are becoming available for IVUS and
the definition of IVUS can be improved using higher frequency
probes. I think the two imaging modalities are nearly at the same
level. The challenge is not so much to convince colleagues who
are already using IVUS to use OCT instead. The challenge is to
increase the critical mass of operators who actually use any form
of imaging be it OCT or IVUS.
Clinic: Since their mechanism differs, what situation
does OCT benefit the most and in what situation does
IVUS function best?
Dr. William Wijns: I think that OCT has limitations for ostial
disease or left main, but all complex interventions will likely
benefit from imaging, whether it is OCT or IVUS. Simple lesions
can most likely be treated adequately by angiographic guidance
alone. It is when the situation becomes complex – bifurcation
stenting, very long stents, calcified vessels, and multi-vessel PCI –
that invasive imaging be it OCT or IVUS will be most beneficial.
Clinic: What criteria are utilized in determining which
to use? And, will ILUMIEN III provide the evidence-
based explanation for the criteria?
Dr. William Wijns: This is a critical question. I think
ILUMIEN III is a very important study because ILUMIEN I has
shown that colleagues tend to overreact to what they see on the
OCT image. This is due to the fact that OCT imaging provides
such detailed information about what happens inside the vessel
with intervention. We see very small dissections, minimal
malapposition, etc. Due to the large amount of information we
see, we tend to react to these details and correct them, which
may prolong the procedure or even cause additional unnecessary
intervention. Hence, it is very important to decide how to react to
the information.
In addition, the hypothesis of ILUMIEN III, that was formulated
by Dr. Gregg Stone, is that the wealth of information provided
by OCT can be reduced to pursue to simple objective, which is
to obtain the largest possible stent area. Although OCT provides
extensive information content, focusing on the dimension of the
vessel itself may well be the essential, clinically-relevant metric to
look for. This strategy will achieve several objectives. We will no
longer over-treat every abnormality that we may see. Secondly,
we know that larger stent areas yield better outcomes. This
6. PCR专家观点
031门诊 CLINIC
PCR Experts Perspective
prevents both stent thrombosis and the need for re-intervention
due to restenosis. It will be very interesting to see whether
physicians can stick to this rule. The hypothesis of the trial is that
you can achieve an equally large stent area whether you use IVUS
or OCT; this approach is testing non-inferiority of OCT. At the
same time, there is a third arm to this study, which is angiographic
guidance alone. Thus the superiority hypothesis of the study is
that using either IVUS or OCT will provide you with larger areas
than angiography. If that is confirmed, it will hopefully create the
charter for designing a proper guidance trial that will evaluate
patient outcomes when using OCT versus angiographic guidance
only during complex PCI.
B. Specifics on the PCR Approach to Education
Clinic: The 2016 EuroPCR Congress will take place
soon in Paris, on May 17-20. Can you provide any
specifics in regards to the PCR approach to education?
Why will this be relevant to a Chinese Audience?
Dr. William Wijns: PCR truly aims to offer clinically-relevant
education, and educate in a way that targets the community of
interventional doctors and their entire team (nurses, technicians,
other professionals). I think our specificity is that we are trying
to address the needs of the interventional community. We plan
our educational activities around the idea of “by and for the
community” with the aim to improve patient outcomes. That is the
basic rationale of all educational efforts of PCR – to address the
needs by delivering programs that are made by and for health care
professionals.
Clinic: What can a Chinese delegate expect for this
year’s EuroPCR?
Dr. William Wijns: I hope we will be able to host many
Chinese delegates this year as we did last year. We have simplified
the structure of the program to allow participants to locate more
easily which sessions they would like to attend – an approach
aiming at “self-directed learning.” We hope this will be successful
and allow the colleagues to leave Paris with their individual
specific questions answered.
In addition, the contributions from the delegates are even more
important this year. Courses are changing in the sense that we
have fewer formal lectures each year. An increasingly significant
portion of the Course is based on the contributions of individual
delegates who share their work, research, innovations, and cases –
cases that were complex, successful, or sometimes less so. This is
the basis for the collective learning at EuroPCR.
C. Creating a Continuous Collaboration Effort
Clinic: China has been increasingly more open to PCI.
In the next few years, it is believed that hundreds to
thousands of centers in China will start carrying out
PCI. In this context, what suggestions do you have for
Chinese cardiology interventionists?
Dr. William Wijns: I think this is a wonderful opportunity
for the worldwide interventional community to share and to
learn. Today, the results of coronary intervention and other
interventional procedures are very positive. As such, it becomes
more and more difficult to improve them. In the past, we could
improve from our own experience mostly because results were
not as good as today. Nowadays, if you are practicing state of the
art intervention, you may not witness many complication cases in
your own patient load and experience. Learning how to prevent
and manage unexpected difficulties or rare complications depends
on the sharing of large experiences. The Chinese interventional
community can contribute to this worldwide learning process.
Because of large numbers that generate “big data”, together we
will be able to identify where there is a need for improvement. In
smaller groups, these needs go unseen. I think that the Chinese
interventional community has a major role to play in helping the
7. 032 门诊 CLINIC
东闻视野·国际瞭望 outlook
worldwide community to improve even further the outcomes of
our procedures, while state of the art interventional care is being
distributed to massive patient groups.
Clinic: We are glad to say that CLINIC and the PCR
Family have established a strategic collaboration. How
will this collaboration maximize our contribution to
those Chinese centers?
Dr. William Wijns: That would be fantastic. We cherish this
collaboration with the journal. I think that sharing information
will be increasingly important and useful. I read with great interest
the articles that you had written after interviewing colleagues
from AsiaPCR / SingLIVE. Also, I saw your article about the
EuroIntervention journal. I think your initiative is a nice vehicle
to share information and also to make colleagues from China and
other parts of Asia better aware of what PCR is trying to achieve
in terms of educational objectives.
Clinic: Finally, could you share with us a goal for the
collaboration between CLINIC and PCR.
Dr. William Wijns: I wish that the exchange and sharing of
collective knowledge and experience between colleagues from
China and all over the world will continue to grow over the next
years. Together we are going to build interventional know-how
that will benefit patients. In this way, high level care will continue
to be distributed widely and reach large groups of patients that
could not benefit thus far. Thank you for the opportunity to
contribute to this effort!
Editor: Yubing Jin Photographer: Hui Chen
William Wijns
Cardiovascular Research Center Aalst, Aalst (Belgium)
The Lambe Institute for Translational Medicine and Curam, National University of Ireland, Galway and Saolta University
Healthcare Group, Galway, Ireland
William Wijns graduated in 1976 from the University of Louvain in Belgium where he trained as a cardiologist until 1981. He
then joined the Thorax Center in Rotterdam where he was actively involved with the first applications of nuclear cardiology,
thrombolysis and coronary dilatation. After spending 1984 and 1985 as a Visiting Associate Professor of Radiological Sciences
at UCLA, William Wijns returned to the University of Louvain in Brussels where he directed the cardiac PET programme and
became Clinical Professor of Cardiology. Since 1994, William Wijns is the CoDirector of the Cardiovascular Center Aalst and
merely active as an Interventional Cardiologist. His clinical research focused on the regulation of coronary blood flow, cardiac
metabolism in ischemic heart disease and more recently, stem-cell based cardiac regenerative medicine. He is a co-founder of
Argonauts and Cardio3BioSciences, now Celyad. He has been a Board Member of the World Heart Federation and the European
Society of Cardiology. He is a past-President of EAPCI, the European Association for Percutaneous Cardiovascular Interventions.
Currently, he is Chairman of PCR, and Course Director of EuroPCR and AfricaPCR.
12. PCR专家观点
037门诊 CLINIC
PCR Experts Perspective
PCR Expert Perspective: Artificial
Intelligence & PCR Family
A. Artificial Intelligence: Not Yet Better Than a
Physician
Clinic: Principally, the physician makes the treatment
strategy based on the variables of a disease of every
individual patient, and all the variables of a patient can
be translated into data. Thus, is artificial intelligence
also applicable to the treatment strategy in the medical
category? Is it able to take the place of the human
brain analysis like it is proved successful in the weiqi
tournament?
Dr. Christoph Naber: Yes, I believe there is a good chance
that artificial intelligence can help the physician make decisions.
The approach to the patient is always very structured. We need to
have a lot of information on the individual patient, and we need to
set it in perspective with what we know about a particular disease.
Computers can digest much more information at the same time
than the human brain can. Nevertheless, I believe there is more to
patient treatment than statistically based decision making. Despite
I am convinced that computers are a very important tool to help
us, I believe that they still fall short when there are individual
decisions to make in medical treatment. The very fine degrees
by which symptoms are worsening or improving which tell us
if a patient is getting better or not will be still hard to tell for an
artificial intelligence. If we take this into account, computers can
be of help, but fortunately they will, at least today, not replace the
doctor in the treatment of the patient.
Clinic: Can we implement the idea of this “Strategy-
making Tree”in weiqi into clinical strategy making?
Will it bring large changes to clinical practice in the
foreseeable future?
Dr. Christoph Naber: This is partly what we already do in
medicine, however, if the likelihood of a patient with certain
symptoms is 80% to have this or that disease, the diagnosis still
can be wrong in 20%. If we simply follow a decision making tree,
the question of right or wrong can never be better than the odds.
It is the combination of scientific knowledge, knowing the odds,
intuition and experience that make a doctor excellent.
The better, however, artificial intelligence becomes in learning
from experience, the better it will be about the decision in the
individual patient. As long as it follows rather a statistical
decision making tree, we will still need the doctor make the
computer’s decision suitable for the individual patient.
In ten years, however, simple data processing of current computers
may have been replaced by artificial learning such as in the case
of the AI which learned to play Weiqi. Then, equipped with the
necessary sensors, and based on the huge amount of information
Dr. Christoph Naber
Background:
The artificial intelligence won the human Weiqi champion?
13. 038 门诊 CLINIC
东闻视野·国际瞭望 outlook
a computer can digest, an AI may become better than a doctor,
and be able to draw the right conclusions with better odds than a
human being.
Thus, let’s see in ten years time and maybe then for certain
diseases the artificial intelligence will bring huge changes to
clinical practice.
Clinic: If artificial intelligence technology is developed,
who will be the supposed developer; should clinical
physicians or engineers be the ones to research and
develop the system including inputting all the clinical
variables / parameters?
Dr. Christoph Naber: I feel that the engineers in this
scenario can provide a lot. In cooperation with behavioral and
neurocognitive scientists they can provide an artificial intelligence
architecture which resembles the human decision making process
very closely. But we also need doctors, since they know which
parameters are relevant, and, we will also need statisticians
who understand the relation of the data that we are putting in
the system. At the end, it will be a collaborative approach by all
human intelligence leading to the best system. Only if people
work together, they achieve the best results.
B. 2016 EuroPCR Congress : The Value of Exchange
Clinic: The 2016 EuroPCR will soon arrive and Chinese
physicians are increasingly open to attending overseas
conferences. What can a Chinese delegate expect to
learn at EuroPCR 2016? And what role do Chinese
physicians play in EuroPCR?
Dr. Christoph Naber: EuroPCR is the largest course on
interventional cardiovascular medicine in the world. But this
alone means nothing. A PCR course has unique features, which
distinguishes these courses from other conferences.
What can Chinese physicians expect when they attend a PCR
course?
For sure, they will find the newest science, devices and
technology, but the main focus of our courses is the exchange of
practical experience.
Colleagues attending EuroPCR can exchange with their colleagues
from Europe, but also from the Americas, Africa, Australia and
from different Asian countries. They can learn new trends and
techniques but can also confirm what they are doing in their daily
practice in a real time reality check e.g. by following the famous
“Learning-“ and “How-should-I-treat-sessions” or the outstanding
live cases in the unbelievable atmosphere of the main arena.
Meanwhile, the PCR community is represented all over the world.
Besides EuroPCR and PCR London Valves, there is Africa PCR,
Gulf PCR, PCR Tokyo Valves, and very important for the Chinese
community Asia PCR and in collaboration with the CIT the highly
interactive PCR-CIT Valve Course in Chengdu.
At EuroPCR and at AsiaPCR we already have a large Chinese
contribution and many Chinese colleagues are coming to
represent their community. The PCR family gains a lot from the
input of these colleagues: China is one of the most innovative
and progressive countries and is as such one of the leading
communities in the interventional field in the world.
I feel that in essence the PCR approach is collective learning.
This is what the PCR community has in common with ai. All of
us are coming from different perspectives and backgrounds but
here we are learning together how to apply the best strategy for
the individual patient, and, only together we are able to determine
how we should react to the newest data that we receive.
14. PCR专家观点
039门诊 CLINIC
PCR Experts Perspective
C. Collaboration: Dedication to Topics that Europe shed
light on
Clinic: As part of our collaboration with the PCR
family, we, the Chinese media, hope to bring more topic-
based interviews with European experts to the Chinese
community. Thus, what would be valuable topics on
which Europe can shed light to our Chinese physicians?
Dr. Christoph Naber: China is an outstanding country; you
have huge centers with an enormous experience in interventional
cardiology. As such, you have all the knowledge in the country.
On the other hand, there are always topics where it may be useful
to learn from each other.
Bioresorbable Vascular Scaffolds, may be such a topic: there is
a lot of experience in Europe, while in the US and China, this
practice is just starting. The US received FDA approval two days
ago (March 16th, 2016) and Chinese device companies have
several interesting scaffolds in development which are just on the
horizon of clinical use. On this topic, European experts and other
members of the PCR family can contribute by exchanging their
good and also less good experiences with the Chinese community.
Another topic is transcatheter valves. Together with CIT, PCR has
established an annual course in Chengdu dedicated to this topic.
In China this topic is relatively new, but the interest and need are
growing rapidly. In this dynamic scenario, this course is thought
to support by facilitating the exchange amongst the Chinese
physicians and with experts from other parts of the world.
For me, this course is also a proof that we always can learn from
each other: the incidence of bicuspid aortic valves, for example,
is much higher in Asia than we ever have seen in Europe. While
we still are unsure if this is a genetic determination or if this is
just because you see the patients here at an earlier age, we will
learn from the Chinese community how to adequately treat such
patients.
Exchange and openness always brings the greatest progress to any
field.
Editor: Yubing Jin Photographer: Hui Chen
Christoph Kurt Naber, Germany
Department of Cardiology and Angiology, Contilia Heart
and Vascular Center
Elisabeth-Krankenhaus Essen
Christoph K. Naber studied medicine at the Ruhr-Universität
in Bochum Germany from 1989 to 1995. After his residency
in Duesseldorf and Essen, he became post-doctoral fellow at
the Institute for Pharmacogenetics of the University of Essen
from 1997 to 1999. In 2000 he returned to clinical medicine
and was promoted assistant director of the department in 2004.
In early 2008 he joined the Clinique Pasteur in Toulouse,
France for a fellowship in interventional cardiology. In the
same year he became Director of Interventional Cardiology
at the Contilia Heart and Vascular Center at the Elisabeth
Krankenhaus in Essen, Germany.
Christoph K. Naber is past-chairman of the German working
group of interventional cardiology (AGIK/DGK) and he is
an active member of the PCR family. He is course-director of
AsiaPCR, course-co-director of EuroPCR and PCR London
Valves. He has served as member of the executive board of
the European Association of Percutaneous Cardiovascular
Interventions (EAPCI) of the European Society of
Cardiology (ESC), and is member of the editorial boards of
EuroIntervention and AsiaIntervention.
17. 042 门诊 CLINIC
东闻视野·国际瞭望 outlook
Development, the Trend of Human Society
——The Story of NOAC
Novel oral anticoagulants (NOACs) have received a great deal of
attention since their advent a few years ago. NOACs have been
received widespread coverage in the news throughout the year.
Despite the media coverage, many questions have arisen in regards
to the orientation of public opinion of NOACs. The ROCKET-AF
Study, the only study of Rivaroxaban that led to FDA approval,
has been questioned. According to report of “Validity of Pivotal
ROCKET AF Rivaroxaban Trial Questioned” by Medscape, the
figures of the Warfarin arm were recorded by the INR Monitor
to be lower than they actually were. This, in turn, made the data
supporting the Rivaroxaban arm appear better in comparison[1,2]
.
Furthermore according to the PINNACLE Registry, NOACs
consumed by atrial fibrillation patients were insufficient. The
PINNACLE Registry also showed that, although the intracranial
hemorrhaging (ICH) caused by NOACs is similar to that of
Warfarin, the rate of non-Intracranial hemorrhaging is somewhat
higher[3]
. Fortunately, a real world study emerged thereafter, the
conclusions of which demonstrate that the application result of
Rivaroxaban and Apixaban in real life resembles that of clinic
trials. Therefore, the effectiveness of Rivaroxaban and Apixaban
have been proved[4]
. Faced with tremendous controversy, Clinic
Journal has undertaken the task of discussing the topic of NOAC
in depth: From the perspective of the author, what is the story of
NOAC?
A. Beginning the Story: The Reason of NOAC’s Advent
The story begins with the reason for the creation of NOAC. Given
the numerous shortcomings of Warfarin, there existed a need for
an better, comparable medicine. With this need, the creation of
NOAC began. The most significant improvement with NOAC is
that there exists no need to monitor the Plasma Concentration.
The therapeutic window of Warfarin is quite narrow, which
requires high accuracy standard of INR (International Normalized
Ratio). As such, the dosing of Warfarin must be adjusted when
there is a minor change in INR. However, the high frequency
of blood tests (once per day from the onset of treatment, once
a week after becoming stable) is unendurable to most patients.
Due to the inconsistent rates of monitoring clinical compliance,
the medication compliance of Warfarin is quite low. In
addition, Warfarin is quite sensitive to Vitamin K Antagonist.
Even a small amount of Vitamin K consumed will lead to a
decrease in the effectiveness of medicine or even offset it. The
insurmountable limitation of Warfarin results in the insufficiency
of its effectiveness in anticoagulation. Nevertheless, Warfarin
remained the only medicine to cure atrial fibrillation for more than
half a century. NOAC was invented on the basis of Warfarin’s
insufficiency. In contrast to the two big flaws of Warfarin, NOAC
has two prominent advantages: NOAC boasts the convenience of
not requiring to monitor the Plasma Concentration and NOAC has
greater stability as it is not affected by food consumption.
The story behind the creation of NOAC indicates that, on the
current stage of global anticoagulation for atrial fibrillation, the
promotion of the usage of NOAC will benefit patients, especially
in China. In China, the monitoring of Warfarin is still inadequate,
and the percentage of atrial fibrillation patients receiving Warfarin
18. 043门诊 CLINIC
述评
Editorial
treatment remains quite low (≈20%), even lower than that of
India. Therefore, increasing the proportion of oral anticoagulants
treatment stands as a top priority in China. NOAC frees many
patients and physicians from the inconvenience of monitoring
INR, which raises the patients’ medication compliance. In
conclusion, as the amount of patients who receive effective
anticoagulants treatment increases, so to will the improvement of
the atrial fibrillation patients’ longevity and life quality increase.
B. Development of the Story: The Community’s Attitude
towards NOAC
The wide usage of NOAC boasts many benefits to the current
available medication. Given these benefits, what is the current
attitude of the medical community towards NOAC?
Judging from the widespread coverage and heated debate among
the experts at the beginning of the year, a great deal of the
community in the community is not supportive of NOAC, which
is demonstrated from two parts: the controversy surrounding
the NOAC study and the support of Warfarin. The controversy
surrounding NOAC mainly stems from two factors: the first lies
in its bleeding risk, which seems not to have any advantage over
Warfarin, and, in some cases, is higher in some minor bleeding
events; and the second is the patients’ meditation compliance in
anticoagulation, which shows no significant improvement over the
traditional medicines.
Another state-of-the-art study of Warfarin is also worth
mentioning – the well-managed anticoagulation with Warfarin
observed in AURICULA that is Sweden National Atrial
Fibrillation Anticoagulation Registry [5]
. In the April of this year,
the 9-year follow-up results were reported: the rate of ICH by
the well-managed Warfarin Treatment is quite low and the all-
cause mortality is also very low. As a result, the author noted
that “Warfarin is still an effective treatment strategy of atrial
fibrillation.” However, attention should be paid to the core of this
study, which stated that Warfarin was “well managed.” In the
author’s opinion, the improvement in the patients’ compliance
under good INR monitoring can also be applied to that of NOAC.
In the end, the author’s conclusive point is that “monitoring is
the essence of the essence” because “monitoring in this study is
the essence of achieving long-term high compliance, and high
compliance is the essence of atrial fibrillation anticoagulation”[6]
.
Bearing this in mind, some believe good monitoring is the
essence of atrial fibrillation anticoagulation. As long as successful
monitoring is secured, the net benefit of Warfarin is the same, if
not higher, than that of NOAC.
However, we see that many doctors are supportive of NOAC
and actively promote the usage of it. Their support is based on
concentrated research and development of the specific universal
reversal agent (commonly referred to as remedy) of NOACs in
all the various forms and mechanism, and some simultaneous
educational projects of improving patients’ compliance.
C. Climax of the Story: NOAC Representing the New
Development Trend
a. The Advent of Spinning Jenny
Though not exactly the same, the community’s attitude towards
NOAC is, to some degree, similar to the industry’s attitude
towards Spinning Jenny.
In 1764, James Hargreaves invented the Spinning Jenny. While,
the path for Spinning Jenny to enter the market was not smooth.
Spinning Jenny was greatly opposed by a large portion of the
spindle community following its conception. The inventor James
and his wife even nearly faced persecution. There existed only one
minor difference between Spinning Jenny and the original spindle:
19. 044 门诊 CLINIC
东闻视野·国际瞭望 outlook
the horizontal spindle was lifted, and one spinning wheel could
run eight vertical spindles. Thanks to Spinning Jenny, the original
spindle’s efficiency of production was increased eightfold. The
Spinning Jenny’s improvements allowed the production of cotton
to increase tremendously in England at that time. As a result
of rising opposition, a group of people one night rushed into
James’ house, broke the “Spinning Jenny”, and burnt down the
house. Why? Actually, the advent of Spinning Jenny challenged
the benefits of the traditional spinners – an already prosperous
industry. At that time, the production of cotton was quite low,
and a short supply led the purchase price to remain quite high.
With the release of the Spinning Jenny, the price decreased as
production rates increased. As a result, the traditional spinners
were unable to maintain comparable profits, leading many
members in the industry to oppose the entry of Spinning Jenny
into the market, and to turn their rage towards the inventor of it.
In addition, the cotton spindled by the Spinning Jenny was not
perfect at the onset of its release. The first underdeveloped models
of the Spinning Jenny, for example, produced cotton that was thin
and easily tore apart. However, that time period represented a time
when industrialization was the trend of human society. At that
time, industrialized technologies began replacing hand-work or
traditional work methods at an unprecedented rate.
The advent of the Spinning Jenny was seen as the start of the first
industrial revolution in England, which changed the history of
all human society. This is neither a success of Spinning Jenny,
nor a success of its inventor James, but a success of societal
development itself. Development is the trend of the human society,
which is unalterable and unhindered. Ultimately, development
always succeeds.
b. Conform to the Trend & Impel the Trend
In many ways, the story of NOAC parallels the story of the
Spinning Jenny. The NOAC story in the author’s pen also has
reached the climax. Currently, a trend has emerged in the field of
anticoagulation for atrial fibrillation. This definitive trend shows
that more patients need to receive anticoagulation treatment and
take oral anticoagulation medicine. As high-frequency monitoring
required in the use of Warfarin stands as an obstacle, NOAC,
which does not require monitoring, has become the latest trend
in the development of comparable medicine. Though NOAC
comes under the guise of the medications including Rivaroxaban,
Apixaban, Edoxaban or Dabigatran, the dawn of the NOAC era is
unavoidable and soon to arrive.
Despite the remaining shortcomings of NOAC, which resemble
the flaws of the original Spinning Jenny, the trend of development
will succeed in the end. This “victory” is not meant to surpass
or defeat the old force; instead, it will overcome the flaws of
the old standard. Following the previously established trend of
development, the new produce (NOAC) will build on the initial
product and overcome its disadvantages to create a more efficient,
effective product – propelling the history of human society
forward and bringing benefits to all of human society.
While Warfarin can solve the problem of the disease individually
with a great deal of success under certain prerequisites, it cannot
solve the problem of the disease collectively. For time tells us that
the “certain prerequisites” are neither universal nor globalized.
Thus, to solve the problem of the diseases within the human
community, NOAC is needed. Despite the inadequacy of NOAC’s
application on personal diseases, at least for now, it will follow the
trend of development and continuously improve to create a near-
perfect product. Faced with this kind of trend, what we are willing
20. 045门诊 CLINIC
述评
Editorial
进步，是人类社会发展的趋势
——新型口服抗凝药的故事
to perceive is how to conform to the new trend as well as how to
impel it.
D. Ending the Story: A Success of Human Development
In the end, it would be wise that the clinical community is not
too conservative in its approach to and acceptance of NOAC. An
opposing attitude towards a new trend will become an obstruction
to its development. It is difficult to imagine that well-educated
practitioners, who have contributed a great deal to the medical
field or clinical course, may become that group of “traditional
workers” who opposed and hindered the development of the
“Spinning Jenny”. In the interest of remaining on the good side of
history, it would be wise to accept the development of new trends.
It may turn out to be a tragedy if the development trend encounters
obstacles.
Fortunately, the development trend of human society typically
achieves a successful ending, just like the Spinner Jenny’s story.
Editorialist: Yubing Jin
新型口服抗凝药物（NOACs）问世不过短短几年，却
一直备受关注。今年年初，NOAC资讯频频报出的同时，
舆论也提出了不少质疑：首先是利伐沙班上市唯一基于的
ROCKET-AF研究有效性遭到质疑，因为华法林组床边INR
监测仪提供的数值较实际低，这导致利伐沙班组的数据更为
美观[1,2]
；接下来PINNALCE注册研究显示美国房颤患者口服
抗凝药物使用不足，同时NOAC颅内出血与华法林相似，并
非颅内出血更高[3]
。幸运的是，一项真实世界研究在这个时候
得出结论称：利伐沙班、阿哌沙班在真实世界的应用结果与
其临床试验基本相似，利伐沙班、阿哌沙班的有效性得以证
实[4]
。面对大量的关注和争议，《门诊》杂志在此时希望触及
NOAC话题的深处：围绕NOAC，究竟发生了是一个怎样的
故事？
一、 故事的开头：NOAC出现的缘由
华法林在半个世纪多以来是房颤抗凝的唯一药物手段。
但临床中华法林存在诸多不足，于是NOAC应需而生。华
法林的治疗窗很窄，对INR（国际标准化比率）有很高的要
求，当INR发生细微的改变，药物剂量必须随之调整；高频
（开始两天一次，稳定后一周一次）的血液检查使很多患者
无法耐受。由于监测依从性难以保障，导致华法林的服药依
从性低下。其次，华法林受维生素K拮抗十分敏感，患者稍
摄入含维生素K的食物，药物疗效将减小甚至抵消。华法林
存在这些不可逾越的局限性，导致倚靠有效抗凝严重不足。
NOAC正是基于这样的背景而获得研发。对应华法林的两大
弱点，NOAC具有不需要监测血药浓度的便捷性，不受饮食
影响的稳定性，最大的意义则是无需监测血药浓度。
26. 研究解读
051门诊 CLINIC
SOCRATES trial
者人群，如加拿大、英国、美国、法国以及德国等仅有
28.3％～35.7％有CYP2C19 LOF基因位点。据已经提交到
JAMA杂志的CHANCE基因亚组分析结果透露，无CYP2C19
LOF基因位点的急性轻型缺血性卒中或TIA患者，其中49％
脑血管事件发生后的90天内再发卒中的相对风险降低（HR＝
0.51；95％ CI 0.35-0.75）。有CYP2C19 LOF基因位点
的急性轻型缺血性卒中或TIA患者，脑血管事件发生后的90
天内再发卒中的相对风险无显著差异（HR＝0.93；95％ CI
0.69-1.26）。综上所述，SOCRATES研究入组患者人群中
高加索人比例较高，根据其他相关研究显示SOCRATES研究
患者基线情况多不利于强化抗血小板治疗，可能对本次试验
结果起到决定性作用。
参 考 文 献
Caro JJ, Huybrechts KF, Duchesne I. Management patterns and
costs of acute ischemic stroke : an international study. For the Stroke
Economic Analysis Group[J].Stroke; a journal of cerebral circulation,
2000.31(3):582-590.
WHO. Media centre, The top 10 causes of death.[accessed May,
2014]; Available from:http://www.who.int/mediacentre/factsheets/fs310/
zh/.
Liu L, Wang D, Wong KS, et al. Stroke and stroke care in China:
huge burden, significant workload, and a national priority[J]. Stroke,
2011,42(12):3651-3654.
Wallentin L, Becker RC, Budaj A, et a1. Ticagrelor versus clopidogrel
in patients with acute coronary syndromes[J]. N Engl J Med, 2009,
361(11):1045-1057.
Liping Liu, MD et al. Neurology. 2015; 85: 1-9.
责任编辑: 李园园
图4. 卒中患者双联与单联抗血小板效果对比
图5. 单发性脑梗死与多发性脑梗死患者抗血小板治疗对比
五、总 结
通过本次试验公布，我们可以得出以下几点小结：1. 试
验主要复合终点两组之间存在明显数值差异，但遗憾的是
只达到临界统计学显著性（P=0.067）。而在预设的7天主
要复合终点事件方面，替格瑞洛组显著优于阿司匹林（P＝
0.01）；2. 次要终点方面，替格瑞洛能够显著减少总的卒中
发生率（P＝0.03）和缺血性卒中发生率（P＝0.046）；3.
对于既往高危且已经服用阿司匹林的患者，改用替格瑞洛能
够带来更多获益；4. 安全性终点方面，替格瑞洛用于急性缺
血性脑血管事件抗血小板治疗安全性良好，与对照组阿司匹
林相当（主要出血P＝0.45）。
最后令人高兴的是，SOCRATES研究亚洲人群亚组结果
将于2016年6月在天坛国际脑血管病会议期间公布。已经完成
的亚组分析将揭示中国人群（包括亚裔人群）是否会从强化
抗血小板治疗中获益。详细结果如何，请同道共同关注天坛
国际脑血管病会议期间SOCRATES亚洲亚组结果的公布！
[1]
[2]
[3]
[4]
[5]
27. 052 门诊 CLINIC
东闻论坛·欧洲脑卒中组织大会 ESOC 2016
脑卒中问题的欧洲视角和研究趋势
——欧洲卒中组织大会见闻
The European perspective and
Research trends of Stroke
大会纵览与亮点：European Stroke Journal创刊
大 会 开 幕 式 上 ， E S O 主 席 、 英 国 格 拉 斯 哥 大 学
（University of Glasgow）Kennedy R. Lees教授介绍了
本次会议的概况。来自95个国家与地区，3000多名医师参加
了ESOC 2016大会。为期3天的会议共接受1230篇论文摘要
（包括203场口头发言、1027篇Poster Presentation），11
个不同主题的分会场（包括房颤与卒中、高血压与卒中等心
脑血管交叉领域）、5个Workshops、15个企业赞助Sessions
和14个继续教育专场，共同构成了ESOC2016的主体学术构
架。ESOC还在会上宣布推出最新学术期刊European Stroke
Journal，由瑞典隆德大学（Lund University）的神经病学
家Bo Norrving教授担任主编。
脑卒中是一个全球性的问题，而且在不同的国家
与地区其主要矛盾也各有特点。这不仅与人种基因差
异、饮食生活习惯等基本因素相关，还牵涉到医疗卫
生水平、高危人群筛查、防控网络建设以及大众健康
宣教等各种内容。前不久召开的中国脑卒中大会更重
视整体防治和管控，而对比5月10～12日在西班牙巴塞
罗那举办的第二届欧洲卒中组织大会也具有其特点。
通过在欧洲卒中组织大会的见闻，能够对比中欧对脑
卒中问题的不同视角，并结合学术研究全球一体化的
趋势，谈谈中国的脑卒中防治有哪些可借鉴之处。
Bo Norrving教授
28. 053门诊 CLINIC
卒中的欧洲视角
the European perspective
最新临床研究：从ARUBA、CLEARⅢ到SOCRATES
对于学术会议而言，能够举办LBCTs（Late Breaking
Clinical Trials）专场，并且让那些发表在NEJM、Lancet
等权威期刊的重要临床试验选择在自己的会议首发，是一件
值得高兴的事情。本次ESOC2016就吸引了包括ARUBA、
CLEARⅢ、ATACHⅡ、CLOTBUSTER、EHCHANTED
以及SOCRATES等多个脑卒中领域重要的临床研究发布。
虽然诸如ARUBA、CLEARⅢ等研究已经在今年2月美
国洛杉矶举行的ISC2016（国际卒中大会）上发表，但是其
内容和研究趋势还是带来了许多启示。比如，来自加拿大的
C. Stapf教授介绍了ARUBA研究，揭示了对于未破裂脑动
静脉畸形，行介入治疗未能带来任何获益反而增加了卒中和
死亡的风险。又比如CLEARⅢ研究中，研究入组500例伴有
轻微颅内出血（ICH）的严重脑室内出血患者，应用阿替普
酶导管给药溶栓治疗，期望能够发现脑功能改善。结果亦未
达到终点，仅格拉斯哥评分等评估显示获益。W. Ziai教授
表示Hanley教授带领的团队正在设计后续研究，或许会在更
为严格的适应证和确切的给药方法的基础上，获得期望的研
究结果。最后公布的SOCRATES研究已经邀请王拥军教授解
读，在此不再赘述。
ATACHⅡ的启示：临床研究该怎么开展？
以上试验未达到研究主要终点，对于研究者以及Sponsor
方来讲当然会有些遗憾。开展研究一定是不容易的，就好
像某位专家昨天在会上进行Disclosure时幽默地自嘲没有任
何利益声明是因为找了很多赞助但没找到。有时候获得了
Sponsor也未必能获得理想的结果。就好像在心血管领域既有
HOPE-3这种一个试验发3篇NEJM让人羡慕的成果，也有更
多提前中止试验的研究让许多人扼腕郁闷。回归起点，开展
试验的目的是为了探索并解决临床问题，其实研究过程中发
现的问题有时候比结果更有价值。
在这方面，有一个非常值得学习的试验和读者分享一
下。在INTERACT系列研究的基础上，由美国明尼苏达
大学开展的ATACHⅡ研究可谓成绩斐然。研究旨在评价
急性脑出血患者早期静脉使用尼卡地平强化降低SBP对入
选患者血肿扩大、血肿周围水肿和3个月结局的影响。本
次会上特别邀请了A. Qureshi教授和Y. Palesch教授介绍
ATACHⅡ研究最新结果与亚裔亚组分析。通过深入了解我
认识到，ATACHⅡ试验的影响力不仅仅在于结果本身，而
是其研究理念、方法和实施效果。JVIN杂志评价ATACHⅡ
试验“Leading the path for clinical trials in the era
of technology and International collaboration.”笔者在
ATACHⅡ Trials官方网站上的Newsletters中，阅读了包括
来自首都医科大学附属北京天坛医院等研究者的各种互动信
息。从某种意义上，ATACHⅡ研究的确指出未来开展临床
研究的思路。另外在研究设计和开展合作非常有学问。究竟
好在哪里不敢班门弄斧妄自指点，建议有兴趣的同道有空去
ATACHⅡ官网看看Newsletters，可能会有所收获。
