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An increasing body of data suggests that East Asian patients have differing risk profiles for both thrombophilia and bleeding compared with Western population. This study was designed to evaluate the relationship of bleeding to platelet function in East Asians undergoing percutaneous coronary intervention (PCI). Patients who had undergone uneventful PCI (n= 301) were prospectively enrolled and bleeding events were evaluated during dual antiplatelet therapy (DAPT) with aspirin and clopidogrel. Platelet function was measured during hospitalisation and at 30-day follow-up by light transmittance aggregometry (LTA) and vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) assay. During 30-day follow-up, 29.2 % of patients (n= 88) experienced post-discharge Bleeding Academic Research Consortium (BARC) complications (24.6 % and 7.0 % of BARC type 1 and 2, respectively). Patients presenting with acute myocardial infarction had fewer episodes of type 1 BARC bleeding (odds ratio: 0.41; 95 % confidence interval: 0.22 to 0.76; p= 0.005). The cut-off of low platelet reactivity (LPR) (20 µM ADP-induced platelet aggregation ≤ 46.1 %; platelet reactivity index ≤ 45.1 %) was the independent determinant of type 2 BARC bleeding (odds ratio: 3.55 and 4.44; p= 0.009 and 0.002, respectively). The first 30-day BARC bleeding episodes were associated with an increased rate of subsequent premature DAPT discontinuation during one-year follow-up (4.7 % vs 11.4 %; odds ratio: 2.60; 95 % confidence interval: 1.04 to 6.50; p= 0.035). In conclusion, among East Asians, mild bleeding episodes are common early after PCI and are associated with premature DAPT discontinuation. Type 2 BARC bleeding episodes are associated with LPR cut-offs measured at 30 days post-discharge.

Guideline recommendations on the use of dual antiplatelet therapy (DAPT) in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention (PCI) have been formulated by both the ACC/AHA and the ESC. These recommendations are based primarily on large, phase III, randomized, controlled trials of the P2Y12 inhibitors clopidogrel, prasugrel, and ticagrelor. However, few East Asian patients have been included in the trials to assess the use of these agents, particularly the newer agents prasugrel and ticagrelor. Additionally, an increasing body of data suggests that East Asian patients have differing risk profiles for both thrombophilia and bleeding compared with white patients, and that a different 'therapeutic window' of on-treatment platelet reactivity might be appropriate in East Asian patients. Furthermore, a phenomenon referred to as the 'East Asian paradox' has been described, in which East Asian patients have a similar or even a lower rate of ischaemic events after PCI compared with white patients, despite a higher level of platelet reactivity during DAPT. Recognizing these concerns, the World Heart Federation has undertaken this evidence-based review and produced this expert consensus statement to determine the antiplatelet treatment strategies that are most appropriate for East Asian patients.

Clinical experiences have suggested that East Asians show the higher risk of warfarin-related intracranial hemorrhage compared with Westerners. Therefore, different target of the International Normalized Ratio (INR) in East Asians (1.6-2.6) has been proposed and adapted in clinical practice. In terms with antiplatelet therapy, recent evidence has supported the concept of "therapeutic level of platelet reactivity" to balance clinical efficacy and safety in patients undergoing percutaneous coronary intervention (PCI) or those with acute coronary syndrome (ACS). In line with the warfarin experiences, multiple clinical and pharmacodynamic data from East Asians have shown their different therapeutic level of platelet reactivity following PCI or ACS ("East Asian Paradox"). Furthermore, like most cardiovascular drugs, P2Y12 receptor blockers have marked interethnic differences in the pharmacokinetics and pharmacodynamics. The currently performed clinical trials evaluating the clinical efficacy and safety of potent P2Y12 inhibitors mostly don't include enough number of East Asians to draw reliable conclusions. Therefore, dedicated research and guideline(s) for East Asians are required before we can apply Western recommendations for potent P2Y12 inhibitors in East Asian population. It is a time to consider the paradigm shift from "one-guideline-fits-all races" to "race-tailored antiplatelet therapy" in treating ACS patients.

Background and Objectives: The contribution of multiple risk factors to peri-procedural myocardial infarction (PMI) in East Asians remains controversial. To assess the influence of clinical or laboratory covariates on PMI in these patients., Methods: Stable patients (n=341) undergoing elective percutaneous coronary intervention (PCI) were enrolled. Platelet reactivity was measured by conventional aggregometry and VerifyNow. Inflammation markers and lipid profile were determined by standard methods. PMI was defined according to Universal definition (troponin I or CK-MB ≥ 3 times the 99th percentile of the upper reference limit)., Results: PMI (defined by troponin I and CK-MB) occurred in 47 (13.8%) and 30 (8.8%) patients, respectively. There was no significant difference in ADP-induced platelet reactivity between patients with vs. without PMI. Patients with PMI (troponin I) had higher levels of 6 μg/mL collagen-induced platelet aggregation (PA) and VerifyNow 'BASE' compared with those without PMI. The combination of '6 μg/mL collagen-induced PA>40%'+'BASE>318' (odds ratio, 14.08; 95% confidence intervals, 1.68 to 111.11; p=0.015) or 'WBC>6550/mm(3)'+'C-reactive protein>2.3mg/L' (odds ratio, 7.75; 95% confidence intervals, 2.49 to 24.39; p<0.001) was associated with an increased risk of PMI (troponin I). The greatest likelihood ratio was observed when cholesterol, inflammation marker and platelet function were combined together., Conclusion: This is the first study to demonstrate that heightened platelet responsiveness to collagen and thrombin may be a risk factor for myonecrosis in patients undergoing elective PCI. The utility of the combining measures of platelet function, inflammation and cholesterol to enhance risk stratification and thus facilitate personalized therapy deserves further study., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: As compared with whites, East Asians more often carry the cytochrome P450 (CYP) 2C19 loss-of-function (LOF) allele with the CYP2C19*3 variant. The influence of the CYP2C19 LOF alleles (*2 and *3) on clopidogrel response and clinical outcomes in East Asians with acute myocardial infarction (AMI) has not been reported. We sought to evaluate the effect of the CYP2C19 variants on clopidogrel pharmacodynamics and long-term prognosis in these patients., Methods and Results: Patients who survived an AMI (n=266) were enrolled in a single-center registry. Predischarge platelet reactivity was assessed with light transmittance aggregometry and the VerifyNow P2Y12 assay; the CYP2C19*2, *3, *17 and ABCB1 3435C>T variants were determined. The primary clinical end point was the composite of cardiovascular death, nonfatal MI, and ischemic stroke. The median exposure to clopidogrel was 21 months (interquartile range, 13-29). The ABCB1 3435C>T was not related to clopidogrel response or cardiovascular events. Carriage of the CYP2C19 LOF variant allele was relatively high (60.9%, n=162; *2/*17=2, *3/*17=1, *1/*2=96, *1/*3=29, *2/*2=20, and *2/*3=14). Platelet reactivity increased proportionally according to the number of the CYP2C19 LOF alleles. In a multivariate regression analysis, the risk of high on-treatment platelet reactivity (HPR) increased depending on the number of CYP2C19 LOF allele [1 LOF allele; odds ratio (OR), 1.8; 95% confidence interval (CI), 0.8 to 4.2, P=0.152; and 2 LOF alleles; OR, 2.8; 95% CI, 1.2 to 6.5; P=0.016]; platelet reactivity and the rate of HPR did not differ between the CYP2C19*2 versus *3 allele carriage. In addition, cardiovascular event occurrence increased according to the number of the CYP2C19 LOF allele; compared with noncarriers, carriers of 1 [hazard ratio (HR), 3.1; 95% CI, 0.8 to 11.6; P=0.089] and 2 CYP2C19 LOF allele(s) (HR, 10.1; 95% CI, 1.8-58.8; P=0.008) were associated with clinical end point. The clinical impact of the CYP2C19*2 versus *3 allele carriage also did not differ., Conclusions: Among East Asian patients who survived an AMI, the CYP2C19 LOF allele carriage appears to affect clopidogrel pharmacodynamics and cardiovascular events according to the number of the CYP2C19 LOF allele; the influence of the CYP2C19*2 and *3 alleles on clopidogrel response and long-term outcomes does not differ.