Since the introduction of Non-Vitamin K Antagonist Oral Anticoagulant (NOAC), there have been many changes in the treatment of atrial fibrillation, one of the typical arrhythmia symptoms. Currently, NOAC is rapidly replacing traditional standard medication therapy, warfarin, taking advantage of the sharp improvement in efficacy and safety as an oral medication.
However, there are concerns about hemorrhage, and some medical professionals are expressing curiosity about the proper use of NOAC by Asians, and Koreans in particular.
Professor Kim Young-hoon김영훈, a physician at the Korea University Anam Hospital고려대안암병원, became the first chairman of the Korean Heart Rhythm Society대한부정맥학회 which was promoted to an academic society early this year. Korea Biomedical Review met with him to discuss the treatment methods of atrial fibrillation and how NOAC is changing the treatment trends of atrial fibrillation.
|Professor Kim Young-hoon, first chairman of Korea Heart Rhythm Society, talks about the changing trends of treating atrial fibrillation with the NOAC, during a recent interview with Korea Biomedical Review.|
Question: At a time when the public awareness of arrhythmia remains low, the launch of the Korean Heart Rhythm Society is highly encouraging. What is your plan as its inaugural chairman?
Answer: Efforts have been insufficient to expand the base of arrhythmia. Irregular pulse is the first and last symptom of heart disease. Despite the rapid increase in the prevalence of various ventricular arrhythmias, including atrial fibrillation, along with the progress of population aging, extensive surveys of prevalence rate and epidemiological studies have remained insufficient. The number of using cardiac pacemakers and ventricular defibrillators also remains at about 10 percent of Japan’s and 5 percent of Australia’s as a percentage of the population.
One of the goals that we have at the Korean Heart Rhythm Society is to emphasize the seriousness of arrhythmia, including atrial fibrillation, and conduct education campaigns to increase awareness. We would like to inform the public about the reality that arrhythmia patients are “undertreated,” and how these conditions can create serious consequences.
Also, our country as a whole has yet to generate international data through a multicenter research. If we don’t set up a platform now, we will run into a situation of being unable to handle the data later. Therefore, we need to conduct a systematic and manifold study of strokes and sudden deaths caused by arrhythmia. Besides, our society plans to cooperate with the cardiopulmonary resuscitation association to prevent cardiac arrest and provide training.
Q: With the advent of new medications including NOAC drugs, the way to treat these conditions have changed from the past.
A: The environment for treating arrhythmia, including new medical technology, medicines, and treatment paradigms, has changed dynamically every two to three years. Accordingly, we need to develop a practice guideline for medical specialists. We have so many other things to do, including efforts to reduce the delays in introducing new technologies, and educating the professionals.
Q: Only a few years ago, there was controversy over the usefulness of NOAC compared with warfarin, but things have changed recently, and now practicing physicians have come to express interests in NOAC.
A: That’s correct. NOAC is popular among practicing physicians now. Arrhythmia is a disease which requires the prescription of medicines according to guidelines, similar to cancer treatments. Arrhythmia patients should receive evidence-based therapies. Therefore, professionals must be well-informed of the guidelines, know how the treatment methods are changing, and what kinds of treatments methods they can use safely. The Korean Heart Rhythm Society has been educating about the NOAC, as well as creating programs to increase awareness of the disease
Q: It has been seven years since the debut of the first NOAC. As the treatment of atrial fibrillation and similar diseases receive insurance benefits, it seems that clinical experiences also have been accumulated.
A: In the beginning, doctors used NOAC only when warfarin was ineffective, like contraindication, and on patients who had hemorrhaged. As the user-friendly NOAC has shifted from non-insured to insured treatments, atrial fibrillation (AF) patients have come to enjoy broader options of therapies, but that has not necessarily solved all economic problems. There are not many of them but some patients, including those who have to use NOAC for a short period, including people who don’t belong to applicable diseases and patients with “catheter ablation” cannot receive insurance benefits.
University hospitals, which monitor patients between six months and a year, have felt difficulties prescribing warfarin, which require periodic monitoring. Practicing physicians have also endured various inconveniences caused by monitoring requirements. That is why until recently, AF patients had had not many places to go. And, these AF patients died from strokes or suffered from the low quality of living resulting from stroke-triggered cognitive disorders.
In addition to the major strokes, NOAC has been able to treat multiple minor strokes (embolism) as well. For this reason, and the fact that it can be readily prescribed, the medication will have positive long-term effects on the patients.
Q: As the usefulness of warfarin has fallen compared with NOAC, its use in the clinical fields will likely decline, too.
A: If there is a mechanical valve, you have no other choices but to use warfarin, and patients with severe diseases such as mitral valve stenosis should continue to use warfarin under a stricter monitoring than before. I am using NOAC for the other patients whenever possible.
Patients should be careful in using NOAC because if they forget its use, their risk of stroke goes up when they shift from warfarin to NOAC, and from NOAC to warfarin, during the period. If the patients have adjusted themselves well to warfarin or have difficulties taking medications without the help of others, they had better choose warfarin. For example, patients who take warfarin prefer the medicine because through the regular INR check-ups, they can check their status and can have confidence that “warfarin is protecting me from the disease.”
On the other hand, NOAC does not have special monitoring systems, and patients can feel little changes, weakening their awareness of the disease. For patients who show these psychological characteristics (including those who are already dependent on warfarin and confident that the medication is lowering the recurrence of strokes, mentally and in all other ways, through the INR checkups), or if they are too old to take the medication alone (including those who are tube-fed or unable to swallow capsules), it is recommended that they take warfarin.
Q: There has been an increase in the announcement of real-world data about NOAC.
A: Randomized Controlled Testing (RCT) is different from conventional clinical fields because the patients are highly targeted and controlled. For example, a doctor might expect to see much bleeding through the data of the studies, but the result could be totally different at the clinical fields. That is why the experiences at the “real-world” are essential
Right now, there are no guidelines that state “at this situation, this medication needs to be used,” so professionals at the field are experiencing the side effects, hemorrhage, inconveniences listed by the patients, and convenience from dosage (one a day or two a day). By sharing these real-world experiences and by turning these into data, it will significantly affect the spread of NOAC.
Q: I heard that you are conducting a real-world study yourself.
A: Currently I am participating in “ETNA AF study” of Edoxaban, and how much of its side effects, death rates, hemorrhage occur in the field. The study also examines the results of patients in countries with similar medical insurance systems, such as Korea and Taiwan. After the study, I believe that we will receive feedback on one or two years of using Edoxaban. We will see how the drug prescription changes are executed on-site, the effectiveness and safety of the medicines and others. Also, I am expecting to have an indirect glimpse into the possibility of inter-NOAC switching
Q: There are reportedly a lot of Koreans and Taiwanese people patients in this NOAC study.
A: There are 2,000 people from South Korea, and 500 people from Taiwan. When we began this study, we thought we wouldn’t be able to gather 2,000 patients, but with the help of 17 different university hospitals in Korea, it was a lot easier than we had expected. In fact, some hospitals have finished registrations.
<About ETNA AF Study>
It is a non-interference type of study to observe the safety of Edoxaban therapy for atrial fibrillation patients in actual clinical conditions. Including 2,500 patients from South Korea and Taiwan, there are going to be at least 30,000 patients participating from Europe and Japan, too. The study’s first goal is to look at patients treated with Edoxaban and gather the various bleeding-related safety data (all kinds of hemorrhage, including from the cranial cavity, deaths from bleeding, and various other side effects). The second objective is to review the efficacy of edoxaban therapy (stroke, SEE, TIA, MACE, VTE, ACS and CV conditions, etc.).
On the other hand, Edoxaban (Product Name: Lixiana Tab) won the domestic approval in August 2015 and received insurance benefits in January 2016. Lixiana was put through phase 3 clinical trial called ENGAGE AF-TIMI48. Though this test, Lixiana reduced major risks by 20 percent compared with warfarin, cutting bleeding from the cranial cavity by 53 percent and fatal hemorrhagic bleeding by 45 percent. Also, one of the biggest differences between other NOAC products is that the patients do not have to eat food with the medication, and it is the only NOAC medication developed in Asia.
Q: What is the meaning of the ETNA AF Study?
A: We are expecting to have the data around 2021. So within the next four or five years, we will have the necessary data to create the “practice guidelines.”
Some medical specialists here tend to stop giving medications to their patients for a week if the patients go through endoscopy, tooth extraction, and scaling. But NOAC is different from warfarin, and even in the case of undergoing a big surgery, they only have to suspend the giving of drugs for only 48 hours. If a patient does not take the medication for five to seven at a time, it increases the chance of a stroke. So other doctors, including the dentists, must consider the overall risk factors of the patients
Q: Many South Koreans are also using the NOAC. What are the advantages and disadvantages of these drugs?
A: Regarding the dangers of hemorrhage, the biggest factor is the age (75 or above) and the conditions of the kidney. The four drugs already released have different rates of excretion to kidneys. Therefore, if patients who are 75 years or more are taking NOAC, the patient must check the conditions of the kidney every six months, or, in the case of healthy people, every 12 months. If they ignore such conditions, there will be people, albeit small in number, exposed to the risks of hemorrhage.
When prescribing NOAC to the patient for the first time, the professionals must have their standards, by the age of the patient, the conditions of the kidney, clinical data, and others. If the patient has a history of hemorrhage, the specialists should consider prescribing Edoxaban first. In the case of Edoxaban, Japan has been using the medication in small doses, and I believe that Korea will follow this trend. Four or five years later, we will need to establish a guideline of small dosage prescription for Koreans or Asians.
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