Recent Evolution of the Treatment of Coronary Artery Disease in China: A Conversation With Ya-Ling Han, MD, PhD.

Abstract

HomeCirculationVol. 136, No. 24Recent Evolution of the Treatment of Coronary Artery Disease in China Free AccessNewsPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessNewsPDF/EPUBRecent Evolution of the Treatment of Coronary Artery Disease in ChinaA Conversation With Ya-Ling Han, MD, PhD Ya-Ling Han, MD, PhD and John D. Rutherford, MB ChB Ya-Ling HanYa-Ling Han Search for more papers by this author and John D. RutherfordJohn D. Rutherford Search for more papers by this author Originally published12 Dec 2017https://doi.org/10.1161/CIRCULATIONAHA.117.032510Circulation. 2017;136:2298–2302Download figureDownload PowerPointYa-Ling Han, MD, PhD, was born in Wuhan, Hubei province, in 1953. She graduated from Haebin Medical University in 1978. She received her doctorate in 1994 from Shanghai Second Military Medical University. She was a visiting scholar at the National Heart Center, Singapore. She is currently a professor and the director of the Department of Cardiology, General Hospital of Shenyang Military Region; the director of the Cardiovascular Research Institute; and the director of the Key Laboratory of Acute Severe Cardiovascular Treatment Research of the Chinese People’s Liberation Army. She is the president of the Chinese College of Cardiovascular Physicians and Chairperson-elect of the Chinese Society of Cardiology.Dr Rutherford asks: Could you describe the scope of clinical cardiac care provided in the Department of Cardiology at the General Hospital of Shenyang Military Region?Dr Ya-Ling Han replies: The Department of Cardiology at the General Hospital of Shenyang Military Region, together with the departments of congenital heart disease and cardiovascular surgery, constitute the cardiovascular institute of the People’s Liberation Army, which is among the top 5 centers in China providing comprehensive care for CVD. Our center is located in Northeast China, an area with the highest prevalence of CAD, so the treatment and prevention of CAD is our major focus.We are a busy center: we perform ≈7000 PCIs, 1400 radiofrequency ablations, 550 pacemaker implantations, 900 congenital heart disease interventions, and ≈2500 cardiovascular surgeries annually, with an overall in-hospital mortality rate of <1%.We have pioneered many facets of CVD treatment in China, including PCI for complicated coronary lesions, CTO of coronary arteries, left main coronary disease, treatment of high-risk patients with AMI, novel antithrombotic strategies for coronary patients, and surgical and percutaneous treatment of complicated congenital heart disease.Over the past 2 decades, you and your team have performed >59 000 percutaneous coronary interventions with high success rates. How did you get started with PCI and how did you develop this large and efficient service?Our journey began in 1994, the year I was appointed Director of the Department of Cardiology. At that time, we were similar to thousands of ordinary, small cardiology departments in China. After 23 years, our department has become 1 of the biggest and most prestigious cardiovascular centers in China, with 265 beds and 11 cardiac catheterization laboratories and high annual interventional volumes. Our path to success was not easy, but I believe we made the right choices at critical moments.Our first choice in 1994 was to be disciplined in deciding the area on which to concentrate. Although my training focused on congestive heart failure, I realized that the unmet needs of PCI therapy for the rapidly rising CAD problem in China provided a great opportunity for our department. In 1999, we established the first independent cardiac catheterization laboratory with an experienced PCI team. This led to new techniques and a rapid increase in the volume of PCIs. This initial success fostered other invasive approaches, including radiofrequency ablations, pacemaker implantations, and peripheral arterial interventions.We next set out to improve and expand the professional skills of our PCI team. In the early developmental stage of PCI in China, we used mostly old-fashioned techniques and strategies. In our region, patients with complicated, clinical presentations, and complex coronary lesions were more prevalent, which called for innovations in PCI techniques and adjunctive pharmacotherapeutic strategies. We started to explore and perfect interventions for CTOs, left main coronary disease, and high-risk patients with AMI, and we began using adjunctive antithrombotic therapy. This led to better success rates for patients with complex coronary lesions and enhanced our professional reputation.Finally, we decided to refocus on clinical and translational research to improve the core competencies of our center and attain world standards. This goal was accomplished by limiting the overexpansion of PCI volume and initiating clinical research projects. We set up our research laboratory and our clinical research team, and we developed a database for 14 subspecialty practice registries reflecting our daily practice. Young physicians were sent abroad to leading cardiac centers to learn clinical research skills instead of PCI techniques. We have now performed hundreds of clinical studies, most of which are multicenter studies, some leading to changes in treatment guidelines. Unexpectedly, the progress in clinical research did not hinder our clinical programs but rather was accompanied by a steady increase in our interventional volumes and success rates.In China you have led numerous multicenter trials. Could you describe the funding and challenges associated with these endeavors?Insufficient funding, an inexperienced research team, a heavy clinical load, and a lack of incentives to perform clinical research were our main challenges. In the past, biomedical research funds from the Chinese government were mostly spent on theoretical or basic research, and resources from industry, especially overseas industry, were limited. Moreover, most Chinese physicians were busy clinically and did not have time to participate in clinical research. We fully understood the important clinical questions before us to address our unmet clinical needs and urgent clinical problems, but we did not have the resources or capability to answer them despite our large patient population. Worse yet, some Chinese physicians gradually became complacent and lost their motivation to perform clinical research, thereby establishing a vicious cycle.More than 10 years ago, my team was aware of the importance of clinical research. Because we were interested and committed to this journey, we devoted ourselves to clinical research without or with only minimal funding.For example, we performed a study to evaluate short-term rosuvastatin therapy for the prevention of contrast-induced acute kidney injury in patients with diabetes mellitus and chronic kidney disease.1 This study was physician-initiated, and we screened >24 000 patients for eligibility and enrolled 2998 patients with little funding. We remain grateful to our colleagues and friends from all 53 participating centers, who conducted a highly successful study despite a foreign expert’s assertion that this was mission impossible.Our situation has since improved substantially. The Chinese government has started to emphasize the control of chronic noncommunicable diseases, including CVD; as a result, many clinical research projects have been funded. Most of our studies on antithrombotic treatment for patients with CAD (such as the BRIGHT randomized clinical trial2) were partially supported by government grants during China’s Twelfth and Thirteenth 5-year plans. With our progressively enhanced profile concerning clinical research, many of our studies related to innovative treatment strategies have been supported by nongovernment grants and industry (eg, CREATE study [Multi-Center Registry Trial of EXCEL Biodegradable Polymer Drug-Eluting Stent] and I LOVE IT 2 study3,4).Another challenge for Chinese physicians conducting clinical research is a lack of dedicated teams and facilities. Compared with the United States and European countries, industry infrastructure for clinical research, including contract research organizations, research site monitoring capability, core laboratory facilities, electronic data capture systems, phase I laboratory infrastructure, and biostatistical support, was underdeveloped in China 10 years ago. We did not have clinical trial management experience, and in the past this may have led to studies with less rigorous quality control. During the last decade, with the support of government authorities and because of market forces, facilities supporting clinical research in China have quickly developed and steadily attained the quality required for conducting first-rate multicenter trials. Professional clinical research teams were established in our center as well as many other Chinese centers. This has led to great progress in improving the level of clinical research study design, initiating and managing trials, and providing robust data analyses and reporting.Lack of domestic development of drugs and devices is another challenge for us. However, unanswered clinical questions are the most important motivation and prerequisite for innovation. We can at least partly address these issues by using novel strategies using postmarketing drugs and devices. The majority of our study hypotheses were conceived based on this principle (eg, using high-loading dose clopidogrel and triple antiplatelet drugs with cilostazol for reducing ischemic events in patients with high-risk ACS),5 utilizing high-dose bivalirudin infusions after PCI for prevention of acute thrombosis, and the use of short-term rosuvastatin for the prevention of contrast-induced acute kidney injury.1 Results from these studies can easily be applied clinically and accepted for use in treatment guidelines after expert consensus in China and Western countries.You have played a pioneering role in the use of adjunctive therapies to improve outcomes after PCI. Where do you see further progress in the field?We have carried out many clinical trials concerning PCI-related antithrombotic therapy and put forward several effective and safe clinical treatment strategies. Since 2002, we have treated high-risk patients with ACS with high-loading (600 mg) and maintenance (150 mg) doses of clopidogrel, or triple antiplatelet therapy with cilostazol, in addition to conventional aspirin and clopidogrel.5 We conducted the world’s first and largest randomized controlled study concerning the duration of DAPT after implantation of the 2nd-generation biodegradable polymer drug-eluting stents.4 Our successful completion of the BRIGHT study confirmed that high-dose infusions of bivalirudin after PCI can overcome the risk of increased acute stent thrombosis.2 In these efforts, our findings benefited patients and changed clinical practice to a certain extent.In the future, I believe 3 areas must be addressed. First, we need a simple and reliable scoring system to assess a patient’s risk of ischemia and bleeding at the initial stage of antithrombotic therapy to help clinicians make rational, individualized, antithrombotic decisions. In this regard, good examples are the CHA2DS2-VASc and HAS-Bled scores, but there is no ideal model for peri- and postoperative PCI ischemia and bleeding risk assessments. The DAPT score is another important attempt to move from clinical research to precision medicine. However, the DAPT score emerged from a randomized clinical study with rigorous inclusion criteria, and efficacy in clinical settings in the real world is yet to be evaluated. It is unlikely that a single predictive system is applicable to all populations because there are significant differences in the inherent risks of ischemia and hemorrhage as well as the response to antiplatelet agents between Eastern and Western populations. Therefore, I believe future research should focus more on obtaining accurate and specialized predictive systems that are applicable for different populations in the world.Second, we need to identify a new method or marker, similar to INR, to determine the optimal therapeutic window for antithrombotic drugs and guide clinical risk assessment and individualized treatment. Platelet function testing methods can predict ischemia and bleeding to some extent but are far from ideal. Supported by our national key research and development project, we are exploring new standards to assess the efficacy and safety of antithrombotic therapy, including cutoff values of various platelet function tests, and a gastrointestinal injury scoring system in patients receiving dual or single antiplatelet therapy. The latter study (URL: http://www.clinicaltrials.gov. Unique identifier: NCT03198741) is now proceeding with the cooperation of cardiologists and gastroenterologists using a novel magnetically controlled capsule endoscopy system.Last, we should be able to provide better care for patients when clinical decisions are difficult, such as in elderly patients or those with renal dysfunction, where risks and benefits of both revascularization and antiplatelet or anticoagulant therapies differ.You have major leadership roles as President of Chinese College of Cardiovascular Physicians and Chairperson-Elect of the Chinese Society of Cardiology. What are the challenges you and your colleagues are facing with respect to prevention and treatment of cardiovascular disease in China, and how are you addressing them?According to our 2016 annual report, there are ≈290 million CVD patients in China. In the next 10 years, this number will continuously grow, with a trend toward a higher prevalence of disease in younger people. We still face great challenges in cardiovascular prevention and treatment. China has 20% of the world’s elderly population and is therefore responsible for the largest number of elderly people. Because aging is an independent risk factor of CVD, the threat will continue to increase. Additionally, a recent national survey estimated the prevalence of diabetes mellitus among adults at 12% and prediabetes at an astonishing 50%, representing 114 million Chinese adults with diabetes mellitus and 493 million with prediabetes. We know that 60% to 80% of patients with diabetes mellitus (particularly patients with type 2 diabetes mellitus) die from CVD. Thus, preventing CVD events in our patients with diabetes mellitus is a high priority. Third, the development of various treatment and prevention strategies for different diseases is not balanced. Interventional cardiac treatment technology and methods have developed rapidly, but in the areas of heart failure, rehabilitation, and prevention, we lag behind. China is vast and has a large number of ethnic groups and uneven regional healthcare development. Currently, we lack data-based healthcare information about our population and the utilization of evidence-based medicine. We presently face these challenges. The guidelines we follow depend largely on information from the United States and Europe, and we face difficulty in formulating strategies for preventing and treating CVD in the most suitable manner for our large and diverse population.The report, “Create a Healthy and Harmonious Life: To Curb the Prevalence of Chronic Diseases in China,” released by the World Bank, indicates that this is a key period for China’s prevention and control programs. We have formulated the following plans: (1) Our strategy should be redirected from the treatment of end-stage diseases to disease prevention. Cardiovascular clinicians need to understand that they should provide evidence-based care, as well as refocus their efforts from cure disease to prevent and cure disease, as well as primarily prevent disease. We must carry out comprehensive healthcare interventions in our communities, improve our services in basic medical health, publicize the prevention of risk factors of CVD, and promote the importance of maintaining a healthy lifestyle with specific measures to achieve this. (2) It is also necessary to introduce advanced treatment concepts and techniques from developed Western countries but also to carry forward the valuable experiences of traditional Chinese medicine with the goal of achieving a mutually integrated and coordinated approach to healthcare. (3) We need to establish a comprehensive biopsychosocial service and care model. This means creating a whole-of-life care system that embraces prevention-standardized diagnoses and treatment rehabilitation and strengthening our cardiovascular physician’s big health concept by paying attention to our patients’ overall physical and mental health and well-being. (4) We must build an evidence-based medical care model to replace our historic empirical model of care. The importance of clinical research in the development of treatment and prevention strategies to manage chronic diseases is self-evident. This innovation in medical science and technology has been included in the macrostrategic planning of the Chinese government, including the themes of “Construction of Healthy China,” “Manufacturing Strategy,” and the “Development of the Belt and Road.” This will provide better policies for the environment and protections for the majority of medical researchers, including cardiovascular physicians and nurses. (5) We need to promote Internet-based medical care, which has been widely used in various areas (eg, guidance on the treatment of ACS in remote areas, application-based management for chronic diseases [hypertension, hyperlipidemia, and chronic heart failure], and deployment of wearable devices for remote vital sign monitoring). Because China has the largest internet population in the world, these methods should be able to develop and spread widely to our citizens in the coming years.It is a large and arduous task for a country with 1/5 of the global population to achieve an inflection point of decreased CVD incidence and mortality, which has been our long-term dream. I sincerely hope and strongly believe that Chinese cardiovascular physicians, our professional associations, and societies will work together, become united, and through coordinated endeavors forge ahead to fulfill our great dream.Abbreviations Used in This ArticleAMI acute myocardial infarctionACS acute coronary syndromesCAD coronary artery diseaseCTO chronic total occlusionCVD cardiovascular diseaseDAPT dual antiplatelet therapyINR international normalized ratioPCI percutaneous coronary interventionDisclosuresNone.FootnotesInquiries related to this profile, or the “Paths to Discovery” series, may be directed to the Editorial Office at [email protected].Circulation is available at http://circ.ahajournals.org.