| Dr. Yusuke Yoshikawa is a member of the Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine in Kyoto, Japan. He recently co-authored a paper published ahead of print on October 5 in Circulation, titled “Validating Utility of DAPT Score in a Large Pooled Cohort from Three Japanese PCI Studies.”
This study demonstrated that the DAPT score successfully stratified ischemic and bleeding risks, although the ischemic event rate was remarkably low even in the Japanese population which had a high DAPT score.
Angioplasty.Org's partner site, TCROSS NEWS, recently interviewed Dr. Yoshikawa regarding the background and the insights of this study, as well as its clinical implications in real world practice. |
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Yusuke Yoshikawa, MD |
Q: The present study is composed of three different Japanese clinical trials (the CREDO-Kyoto PCI/CABG Registry Cohort-2, RESET, and NEXT) in different time periods. What were the reasons for including these specific studies?
Dr. Yoshikawa: The present study originally aimed at validating the efficacy of the DAPT score in the Japanese population. However, the study endpoint rarely occurred and thereby required an increase in sample size. So we pooled patients from these three studies and successfully validated the endpoint with more than 10,000 patients. Although these studies were conducted in different contexts, the CREDO-2 enrolled in a series of real-world population, and RESET and NEXT are RCTs without establishing exclusion criteria.
Q: In those patients with a high-DAPT-score, the cumulative incidences of cardiac death, myocardial infarction and stent thrombosis were significantly greater, while the cumulative incidences of non-cardiac death and GUSTO severe bleeding were significantly lower. What is the significance of these findings?
Dr. Yoshikawa: The present study demonstrated the effectiveness of the ischemic and bleeding risk stratification using the DAPT score even in the Japanese population. The major difference between our study and the DAPT study is the presence or absence of randomization based upon the DAPT period. The DAPT study, which randomized antiplatelet therapy after 12 months, is appropriate to evaluate effectiveness of long-term DAPT by score. On the other hand, duration of DAPT during the follow-up in the present study was at the discretion of physicians. In other words, DAPT was continued when the physician believed benefit outweighed harm, but the opposite was true when harm outweighed benefit. Nevertheless, the present study demonstrated the tendency that the ischemic event rate was higher in the high-DAPT-score cohort, whereas the bleeding event was higher in low-DAPT-score.
Q: In the present study, the DAPT status (on or off) at 13 months failed to show a statistical significance in both the high and low DAPT-score. What is the clinical implication of this outcome?
Dr. Yoshikawa: The present study demonstrated that on-DAPT at 13 months tended to be at a lower risk for ischemic event in high DAPT score and at a higher risk for bleeding event in low DAPT score, although the differences were not statistically significant. This finding is similar in the original DAPT study. However, whether the results were significant or not, the present study would be underpowered to impact the clinical practice. As mentioned above, the duration of DAPT was not randomized, but rather at the discretion of each attending physician. On-DAPT at 13 months is a substitute for long-term DAPT in our study, which includes those who discontinued DAPT after 13 months, whereas off-DAPT includes those who restarted DAPT thereafter. Despite the adjusted baseline characteristics using propensity scoring, the study design did not sufficiently evaluate drug efficacy. Further study evaluating the effectiveness of the DAPT score in a different cohort, randomized by DAPT periods, is needed.
Q: The investigators suggested the presence of regional and racial differences in the ischemic and bleeding events. From your point of view, which patients require long-term DAPT?
Dr. Yoshikawa: In general, Japanese patients are less likely to experience ischemic events than bleeding events. This trend is totally opposite in patients in Western countries where ischemic events outweigh bleeding events. Therefore when considering who requires long-term DAPT, we also focus on who should avoid long-term DAPT. A feature of the DAPT score is stratification of both ischemic and bleeding risks in the single score. Considering the DAPT duration, early termination is prudently considered for patients with lower DAPT score.
Q: What proportion of patients in Kyoto University Hospital continue DAPT more than 12 months? Also, which agents are used for DAPT (aspirin + clopidogrel/prasugrel)?
Dr. Yoshikawa: Most patients in the Kyoto University Hospital are currently enrolled in the ongoing STOP DAPT-2 trial. In this study, post PCI patients are randomized to either the 1-month or the 12-month DAPT group. For patients excluded from the trial, DAPT duration is at the discretion of the physicians in charge, and 3- to 6-month DAPT is common. Regarding thienopyridine, loading in many cases is performed in the catheterization lab before ad hoc PCI. We basically administer prasugrel for loading, and switch to clopidogrel in maintenance period. We use the same antiplatelet agents for patients with acute coronary syndrome and stable angina (according to the STOPDAPT-2 trial protocol).
Q: What is the most important finding in the present study?
Dr. Yoshikawa: Since DAPT became the standard practice following PCI, various clinical trials searching for appropriate DAPT durations have been conducted. However, DAPT durations in previous studies ranged from a few months to a few years. Therefore, we should carefully consider applying previous evidence to individual patients. Ischemic event and bleeding events are contradictory, but the risks for these events have many characteristics in common, resulting in making a treatment individualization difficult. The present study aimed at verifying the DAPT score in Japanese patients who have different risks as compared with Western patients. The study reflected the trend of Japanese patients who have low ischemic risk and high bleeding risk, and observed successful stratification as well.
I would not have been able to conduct this study without support from my colleagues. I would like to offer my great sincerity to all who helped me accomplish the present study. Thank you very much.
This interview was conducted in October 2017
by TCROSS NEWS, Tokyo, Japan |
