Asian perspective on the recently published practice guideline for acute coronary syndrome by ESC

The European Society of Cardiology (ESC) has recently issued an updated set of guidelines pertaining to the management of acute coronary syndrome (ACS).1 Typically, these guidelines are formulated based on the findings of randomized clinical trials, which serve as the cornerstone of evidence-based medicine. Historically, clinical trials in the field of ACS have been conducted with the underlying assumption that patients suffering from this condition share a degree of uniformity across different geographic regions. Consequently, the ESC's ACS guideline is intended to serve as a benchmark for the care of the average ACS patient on a global scale. It is important to note that these guideline recommendations are designed to be applicable and relevant to most individual ACS patients. Nonetheless, it is essential to acknowledge that there exist certain variations and heterogeneities in the prevalence of ACS, associated risk factors, prevailing treatment modalities, and clinical outcomes across diverse regions worldwide. With this in mind, we aim to provide a unique perspective from an Asian standpoint regarding the recently released ESC guideline for ACS. Acute coronary syndrome includes unstable angina, non-ST-elevation myocardial infarction, and ST-elevation myocardial infarction. The Global Burden of Disease (GBD) Study 2019 studied 369 diseases and injuries in 204 countries and territories from 1990 to 2019.2 The GBD provides a comprehensive picture of the burden of various diseases, including ischaemic heart disease (IHD). While the GBD does not provide specific information for ACS, important information for predicting the future of ACS in various regions, including age-adjusted prevalence and incidence of IHD, cardiovascular disease mortality, and mortality due to IHD, are available from this study. These data provide a speculative view of the ACS disease burden in Asia. One interesting finding in GBD is the decreasing trend in age-adjusted prevalence and incidence of IHD from 1990 to 2017.3 This does not mean that the global burden of ACS is decreasing. Instead, it reflects the substantial growth in the global population, and thus, the absolute numbers of patients with IHD are increasing despite the apparently lowering ratio against the entire population3 (Figure 1). The GBD data show substantial regional heterogeneity in the risk of death due to IHD across the globe. From these data, one may argue the potential difference between the European Union (EU) and Asian countries in regard to the burden of ACS. However, it is important to note that the intra-region heterogeneity was even larger than the inter-region heterogeneity. The age-standardized death rates due to IHD in 2019 were highest in Central Asia {360.0 [95% uncertainty intervals (UI): 330.9–390.2] per 100 000 population}. The relatively high risk of IHD death was also shown in Eastern Europe [284.6 (95% UI: 253.6–310.1) per 100 000 population]. The data also suggest that there are substantial heterogeneities within Europe, showing that the IHD death rate in Western Europe at the same time was [60.7 (95% UI: 54.2–64.9) per 100 000 population]. It is of note that the IHD death rate was even lower in high-income Pacific regions including East Asian countries. [30.5 (95% UI: 25.7–33.3 per 100 000 population)] In summary, there are substantial regional heterogeneity in the risk of IHD death rates across the globe. However, the inter-regional heterogeneity of IHD death between the EU and Asia is within the intra-regional heterogeneity in both regions. Deaths due to ischaemic heart disease in 1990 and 2019 and percentage change in the age-standardized rates per 100 000, by region. ASRs, age-standardized rates; IHD, ischaemic heart disease. It is reasonable to assume that ACS, which is the major contributor to IHD death, has similar impacts on the Asian population, just like other regions of the world. Updated ESC guideline is expected to reduce the ACS burden on the globe, including the Asian region. A highlight of the new recommendation in the guideline regarding the risk factors is the addition of long-term glucose-lowering therapy in ACS patients comorbid with heart failure, chronic kidney disease, and obesity as Class I, evidence level A.4 This is reasonable and timely. The GBD data indicated the importance of high systolic blood pressure, high low-density lipoprotein cholesterol, smoking, high fasting plasma glucose, and high body mass index (BMI) as the contributing factors for IHD.3 The risk factor control is the most important step for preventing ACS. For the Asian perspective, it should be noted that the definition of the overweight and obesity based on BMI in Asian countries is lower than in other regions of the world.5 Both the risk of diabetes mellitus (DM) and cardiovascular (CV) events become higher in Asian patients even with a BMI <25 kg/m2.6 For applying updated ACS guidelines to Asian patients, physicians should be careful about hidden type 2 DM in patients who do not appear as Obese based on the guidelines. The new or changed recommendations in the updated ESC ACS guideline, focusing on Classes I, IIa, and III with an Asian perspective, are summarized below. Platelet and fibrin are the major components of thrombi causing ACS.7 Both antiplatelet and anticoagulant therapy play major roles in ACS patients. There are several important updates in this version. Resumption of dual antiplatelet therapy (DAPT) after coronary artery bypass surgery when the patients stopped DAPT before coronary arterial bypass graft looks reasonable, but the supporting clinical evidence is scarce. The recommendation of single antiplatelet therapy, preferably P2Y12 inhibitor, after 3–6 months, is reasonable with supportive clinical evidence.8–10 De-escalation of antiplatelet therapy in the first 30 days is not recommended. These new recommendations are all reasonable and do not need a region-specific perspective, except for the use of prasugrel in Japan. The dose of prasugrel approved in Japan is approximately one-third11 as compared to the dose used in the TRITON TIMI 38 study.12 Low dose of 3.75 mg prasugrel is also approved in Taiwan and Indonesia. Physicians taking care of ACS in some countries in Asia should be aware that the local does of prasugrel in Japan differ substantially from the dose recommended on this updated practice guideline. Despite scarce clinical evidence, the Class I recommendation of neurological function assessment no earlier than 72 h after admission for all comatose survivors is reasonable. The Class IIa recommendation of transport to the cardiac arrest centre is also reasonable. However, cardiac arrest centres may not be widely available in Asian countries. The updated ESC guideline recommends percutaneous coronary intervention (PCI) for spontaneous coronary artery dissection at Class I only in the presence of a large perfusion area of the myocardium supported by symptoms and signs. This is only supported by scarce clinical evidence.13 The Class I recommendation of Intravascular imaging to guide PCI is recommended as Class IIa with strong clinical evidence.14,15 If the ACS patients present with cardiac shock, staged PCI of the non-infarct related arteries based on angiographic severity is recommended as Class I with evidence level B.16 If the ACS patients are not presented with cardiogenic shock, immediate multivessel PCI was non-inferior to staged multivessel PCI.17 The angiographic evaluation is conducted intuitively by experts. This allows substantial heterogeneity in treatment based on physician's decisions. The invasive epicardial assessments of non-culprit regions during index PCI is not recommended. These new recommendations are all reasonable and do not require region-specific statements. The recommendation to implant a permanent pacemaker for advanced atrio-ventricular block 5 days after myocardial infarction is Class I, but the clinical evidence is not strong. Recommendation of magnetic resonance imaging in suspicious LV thrombi is Class IIa but without strong clinical evidence. Again, long-term glucose-lowering therapy is recommended as Class I with evidence level A. The recommendation of the initialized holistic approach in frail elderly patients is important, especially in eldering East Asian countries. For high-risk ACS patients comorbid with cancer, an invasive strategy is recommended if the life exception is longer than 6 months. The prognosis of cancer patients improved substantially within the last 2 decades. This means the probability of ACS patients with cancer should increase despite the fact that only a limited amount of clinical evidence is available so far.18 Some cancer therapies influence the risk of CV events, including ACS.19 Temporal interruption of cancer therapy in ACS patients is recommended at Class I but with scarce clinical data. There is a wide variety of cancer therapies, and not many cardiologists possess detailed knowledge about them. Perhaps cardiologists should communicate closely with cancer specialists when taking care of these specific patients. The Class IIa recommendation of a conservative strategy in cancer patients with poor prognosis and high risk of bleeding may be fine, but caution is necessary for using strong antithrombotic therapy even as a conservative strategy. Platelet plays an important role in haemostasis. The Class III recommendations for using aspirin, clopidogrel, prasugrel/ticagrelor in patients with platelet counts <10 000/mL, 30 000/mL, and 50 000/mL are not based on clinical evidence. It is hard to use antiplatelet agents in patients with reduced platelet counts. These Class III recommendations may help interventional cardiologists take care of these difficult patients. In some countries in Asia, cancer is the most common cause of death. Cardiologists in these countries should carefully apply this ESC practice guideline to their ACS treatment locally because the psychological impact of cancer is larger in these countries as compared to the EU countries. Intense lipid-lowering therapy during index ACS hospitalization in patients who were already on lipid-lowering therapy is a class I recommendation but with evidence level C. From an Asian perspective, side effects of statin in Asian patients at high dose are quite common. It is of note that the dose of statin used in East Asian countries is approximately half the standard dose in the EU. Indeed, in the recent clinical trial, the standard and intensified dose of atorvastatin were defined as 10 and 20 mg/day in China and Japan, whereas they were defined as 20 and 80 mg in the other regions of the world.20 Careful and region-specific considerations are necessary before increasing the dose of statin in Asian patients. Even though the clinical evidence is not rich, patient-centred care is necessary. The values of life in individual patients might differ in Asia as compared to the EU countries. It would be important to hear the preferences of individual patients. It is also important to include ACS patients for the decision making process. The risk of adverse events, radiation exposure, and alternative options should be shared between physicians and patients. The ‘teach-back’ technique is recommended to ensure ‘informed consent’ and to let the patients understand what they have to do after discharge at Class IIb with evidence level B. The importance of mental ‘well-being’ with psychological referral may be required. Recently published ESC practice guideline for ACS patients includes important new recommendations. Most of the new recommendations were based on the global clinical evidence or intuitions by interventional cardiologists. There is huge homogeneity in the disease burden, risk factors, current treatments, and intuitive feelings across the globe. New ESC guidelines for ACS should help improve the clinical outcomes of ACS patients around the globe, including Asia. The corresponding author Shinya Goto acknowledges the receipt of grant-in-aid for MEXT/JSPS KAKENHI 19H03661, AMED grant number A368TS, A447TR, the 16th Nakatani Grand Prix award, the Vehicle Racing Commemorative. Foundation (6301, 6374), and the Fukuda Foundation for Medical Technology. No new data were generated or analysed in support of this research.