East Asian Paradox Research Articles

“East Asian Paradox” Revisited: Precision Medicine for Antithrombotic Strategies Tailored to Atherothrombotic Cardiovascular Risks

“East Asian Paradox” Revisited: Precision Medicine for Antithrombotic Strategies Tailored to Atherothrombotic Cardiovascular Risks

Impact of Low-Dose Prasugrel on Platelet Reactivity in Chronic Phase of Post-Percutaneous Coronary Intervention (CHAPERON): a Prospective Cohort Study.

Asians often face the problems of clopidogrel resistance and East Asian paradox. This study aimed to evaluate the effects of P2Y12 inhibitors, including low-dose prasugrel 2.5mg, on the P2Y12 reaction unit (PRU) in the chronic phase after percutaneous coronary intervention (PCI). A total of 348 patients were studied. PRU was measured 6-12months after PCI and subsequently, 6months later using a P2Y12 assay, respectively. This study evaluated the proportion of bleeding risk (PRU ≤ 85) and ischemic risk (PRU ≥ 239) as primary endpoints, and the prediction of bleeding risk and ischemic risk using multivariable logistic regression analysis. At baseline, 136 patients (39%) received prasugrel 3.75mg, 48 patients (14%) received prasugrel 2.5mg, and 164 patients (47%) received clopidogrel 75mg. Clopidogrel 75mg had a significantly higher proportion of ischemic risk within one year after PCI than the other groups, and was an independent predictor for ischemic risk with reference of prasugrel 3.75mg. In addition, switching from clopidogrel 75mg to prasugrel 2.5mg significantly lowered and aggregated the PRU value. Whereas, dose reduction of prasugrel had a significantly lower proportion of bleeding risk over one year after PCI than the continuation of prasugrel 3.75mg, and was an independent predictor for bleeding risk with reference of continuation of prasugrel 3.75mg. Prasugrel 2.5mg has a lower ischemic risk and a more stable PRU value compared with clopidogrel treatment. Prasugrel also contributes to a decline in bleeding risk with concomitant dose reduction. University Hospital Medical Information Network (UMIN), ID: UMIN000029541, Date: October 16, 2017 ( https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000033395 ).

Antiplatelet Therapy Aims and Strategies in Asian Patients with Acute Coronary Syndrome or Stable Coronary Artery Disease.

Dual antiplatelet therapy (DAPT) has been the mainstay treatment to reduce ischemic events, such as myocardial infarction or stroke, in patients with coronary artery disease (CAD). The development of potent P2Y12 inhibitors (ticagrelor and prasugrel) has helped to further reduce ischemic events, particularly among high-risk patients. Meanwhile, the evolution of newer generations of drug-eluting stents are also improving outcomes of percutaneous coronary intervention. Research studies on antiplatelet therapy in recent years have focused on balancing ischemic and bleeding risks through different strategies, which include P2Y12 inhibitor monotherapy, escalation and de-escalation, and extended DAPT. Because results from the large number of clinical studies may sometimes appear conflicting, this review aims to summarize recent advances, and demonstrate that they are aligned by a general principle, namely, strategies may be adopted based on treatment aims for specific patients at several time points. Another aim of this review is to outline the important considerations for using antiplatelet therapy in Asian patients, in whom there is a greater prevalence of CYP2C19 loss-of-function mutations, and a common increased risk of bleeding, despite high platelet reactivity (the so-called "East Asian Paradox").

Antithrombotic Therapy After AcuteCoronary Syndromes or Percutaneous Coronary Interventions inEast Asian Populations.

Because guidelines and recommendations in response to multiple randomized clinical trials (RCTs) of new therapies undergo rapid changes, antithrombotic therapies for patients after acute coronary syndrome, or percutaneous coronary intervention, are becoming more complex in daily clinical practice. The proportion of Asian populations enrolled in landmark RCTs is substantially low, which limits the direct application of trial findings into clinical practice in Asian countries. Moreover, compared with Caucasian patients, East Asian patients are considered to have a different ischemia/bleeding propensity in response to antithrombotic therapy, known as the "East Asian paradox" (ie, more bleeding events but fewer thromboembolic events). Coincident with consecutive RCTs in Western populations to optimize antithrombotic strategies, several such studies have now been conducted in East Asian cohorts. Herein, we provide a comprehensive summary of the key RCTs in this regard and propose future directions and perspectives for optimal antithrombotic therapies in East Asian patients.

Effect of CYP2C19 status on platelet reactivity in Taiwanese acute coronary syndrome patients switching to prasugrel from clopidogrel: Switch Study

Pharmacogenetics is a potential driver of the "East Asian paradox," in which East Asian acute coronary syndrome (ACS) patients receiving dual antiplatelet therapy (DAPT) with clopidogrel following percutaneous coronary intervention (PCI) demonstrate higher levels of platelet reactivity on treatment than Western patients, yet have lower ischemic risk and higher bleeding risk at comparable doses. However, the impact of pharmacogenetics, particularly regarding CYP2C19 genotype, on the pharmacodynamics of P2Y12 inhibitors has not been extensively studied in Taiwanese ACS patients as yet. CYP2C19 genotyping and pharmacogenetic analysis was conducted on 102 subjects from the Switch Study, a multicenter, single-arm, open-label intervention study that examined the effects on platelet activity and clinical outcomes of switching from clopidogrel (75mg daily) to low-dose prasugrel (3.75mg daily) for maintenance DAPT after PCI in 203 Taiwanese ACS patients. Genotyping results revealed that 43.1% were CYP2C19 extensive metabolizers (EM), while 56.9% were reduced metabolizers (RM). After switching to prasugrel, mean P2Y12 reaction units (PRU) values were significantly reduced in both EM and RM populations, while the proportion of high on-treatment platelet reactivity (HPR) patients significantly declined in RM patients. No increase in bleeding risk after switching was observed during follow-up. Multivariate analysis indicated that for RM patients, low estimated glomerular filtration rate (eGFR) and low hemoglobin were associated with greater HPR risk on clopidogrel, but not after switching to prasugrel. Switching to low-dose prasugrel from clopidogrel reduced mean PRU levels and proportion of HPR patients, with more significant reduction in RM patients.

The East Asian Paradox: An Updated Position Statement on the Challenges to the Current Antithrombotic Strategy in Patients with Cardiovascular Disease.

East Asian patients have reduced anti-ischemic benefits and increased bleeding risk during antithrombotic therapies compared with Caucasian patients. As potent P2Y12 receptor inhibitors (e.g., ticagrelor and prasugrel) and direct oral anticoagulants are commonly used in current daily practice, the unique risk-benefit trade-off in East Asians has been a topic of emerging interest. In this article, we propose updated evidence and future directions of antithrombotic treatment in East Asian patients.

Safety and Effectiveness of Contemporary P2Y12 Inhibitors in an East Asian Population With Acute Coronary Syndrome: A Nationwide Population-Based Cohort Study.

BackgroundPrior reports indicate that the effect of P2Y12 inhibitors may be different in East Asian patients (“East Asian paradox”); therefore, understanding the outcomes associated with potent P2Y12 inhibitors in different populations is clinically important.Methods and ResultsIn this observational cohort study using administrative healthcare data sets, we compared safety and effectiveness of contemporary P2Y12 inhibitors in patients with acute coronary syndrome. The primary safety outcomes were major and any bleeding, and the primary effectiveness outcomes were major cardiovascular events (a composite of cardiovascular death, myocardial infarction, or stroke) and all‐cause mortality. Among 70 715 patients with acute coronary syndrome, 56 216 (79.5%) used clopidogrel, 11 402 (16.1%) used ticagrelor, and 3097 (4.4%) used prasugrel. The median follow‐up period was 18.0 months (interquartile range: 9.6–26.4 months). In a propensity‐matched cohort, compared with clopidogrel, ticagrelor was associated with a higher risk of any bleeding (hazard ratio: 1.23; 95% CI, 1.14–1.33) but a lower risk of mortality (hazard ratio: 0.76; 95% CI, 0.63–0.91). Prasugrel, compared with clopidogrel, was associated with higher risks of any bleeding (hazard ratio: 1.23; 95% CI, 1.06–1.43) and major bleeding (hazard ratio: 1.50; 95% CI, 1.01–2.21) but a similar risk of effectiveness outcomes. No significant difference was noted between ticagrelor and prasugrel with respect to key safety or effectiveness outcomes. Several sensitivity analyses showed similar results.ConclusionsIn East Asian patients with acute coronary syndrome, compared with clopidogrel, ticagrelor was associated with an increased risk of bleeding but a decreased risk of mortality. Prasugrel was associated with an increase of any bleeding without difference in effectiveness outcomes. The risks of bleeding and ischemic events were similar between ticagrelor and prasugrel.

Should Antithrombotic Treatment Strategies in East Asians Differ from Caucasians?

With over 1.5 billion people, East Asians are the most populous race in the world. Health status in this population is an important global issue. In the contemporary trials of antithrombotic treatment, East Asian patients have a lower risk for atherothrombotic diseases (especially, Coronary Artery Disease [CAD]) and a higher risk for bleeding (especially, gastrointestinal bleeding and hemorrhagic stroke). Despite these observations, antithrombotic treatment strategies in East Asian patients are mainly based on the American or European guidelines that are derived from randomized, controlled trials including mostly Caucasians. Despite a low response to clopidogrel, East Asian patients with CAD show a similar or even a lower rate of ischemic event occurrence and higher bleeding risk compared with Caucasian patients. The latter is referred to as the "East Asian Paradox", suggesting a dissimilar therapeutic window for antiplatelet therapy than Caucasians. In addition, different net clinical benefits have been observed between the races with potent P2Y12 inhibitors that may be related to racial differences in pharmacokinetic and pharmacodynamic profiles. Furthermore, there is emerging concern regarding differences between East Asian vs. Western patients in pharmacodynamic and clinical efficacies of anticoagulant agents. We now summarize experimental and clinical evidence of the efficacy and safety of antithrombotic agents in the East Asian population. We suggest the concept of "race-tailored antithrombotic treatment" in CAD patients and/or in patients undergoing percutaneous coronary intervention.

The Evolving Concept of Dual Antiplatelet Therapy after Percutaneous Coronary Intervention: Focus on Unique Feature of East Asian and "Asian Paradox".

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is essential after percutaneous coronary intervention (PCI), while many studies have focused on determining the optimal degree of platelet inhibition and optimal DAPT duration to minimize complications after PCI. Current guidelines developed by the American College of Cardiology/American Heart Association and the European Society of Cardiology summarize previous studies and provide recommendations. However, these guidelines are mainly based on Western patients, and their characteristics might differ from those of East Asian patients. Previous data suggested that East Asian patients have unique features with regard to the response to antiplatelet agents. On comparing Western and East Asian patients, it was found that East Asian patients have a lower rate of ischemic events and higher rate of bleeding events after PCI, despite a higher on-treatment platelet reactivity, which is referred to as the “East Asian paradox.” As the main purpose of DAPT is to minimize ischemic and bleeding complications after PCI, these differences should be clarified before adopting the guidelines for East Asian patients. Therefore, in this article, we will review various issues regarding DAPT in East Asian patients, with a focus on the unique characteristics of East Asian patients, previous studies regarding antiplatelet agents in East Asian patients, and a guideline from an East Asian perspective.

Using Pharmacogenetic Testing or Platelet Reactivity Testing to Tailor Antiplatelet Therapy: Are Asians different from Caucasians?

All studies to date involving platelet reactivity and gene testing document singular interventions and their associations with outcomes. The East Asian paradox has been well documented - Asians who have had a percutaneous coronary intervention (PCI) are at a lower risk of ischaemic events even though they have a higher platelet reactivity. Asians who have had a PCI also have a higher risk of bleeding. This article covers the differences in outcomes between Caucasians and Asians, and explores the impact of outcomes, highlighting differences between the two patient populations. Given the high prevalence of loss-of-function alleles in Asia, treatment strategies will differ for different populations. It is plausible that both platelet reactivity and gene testing should be used to inform holistic decision-making for all patients - Caucasian or Asian - with acute coronary syndrome who are undergoing PCI.

Expert consensus document: World Heart Federation expert consensus statement on antiplatelet therapy in East Asian patients with ACS or undergoing PCI.

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.

“East Asian Paradox”: Challenge for the Current Antiplatelet Strategy of “One-Guideline-Fits-All Races” in Acute Coronary Syndrome

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.

Corruption and firm growth: Evidence from China

Corruption is one of the most pervasive obstacles to economic and social development. However, in the existing literature it appears that corruption seems to be less harmful in some countries than in others. The most striking examples are well known as the “East Asian paradox”: countries displaying exceptional growth records despite having thriving corruption cultures. The aim of this paper is to explain the high corruption but fast economic growth puzzle in China by providing firm-level evidence of the relation between corruption and growth and investigating how financial development influences the former relationship. Our empirical results show that corruption is likely to contribute to firms' growth. We further highlight the substitution relationship between corruption and financial development on firm growth. This means that corruption appears not to be a vital constraint on firm growth if financial markets are underdeveloped. However, pervasive corruption deters firm growth where there are more developed financial markets. This implies that fast firm growth will not be observed until a later stage of China's development when financial markets are well-functioning and corruption is under control. Furthermore, the substitution relationship exists in the private and state-owned firms. Geographically, similar results can be seen in the Southeast and Central regions.

A behavioral theory of governments’ ability to make credible commitments to firms: The case of the East Asian paradox

An expansive literature exists linking institutional constraints, credible commitments, and economic growth. Yet, this literature runs into difficulty when it tries to explain the East Asian “paradox:” rapid economic growth achieved by countries with low levels of formal constraints on government discretion. We use a behavioral theory of commitment to argue that the characteristics of the salient actors (governments) and their actions (policies) affect the credibility of their behaviors in ways independent of the structural underpinnings of a country’s political institutions. This behavioral theory of commitment provides a distinct but complementary lens through which to view the apparent paradox presented by these East Asian countries, and more generally provides an alternative theoretical mechanism to explain and predict governments’ ability to credibly signal their commitment to a course of action to investing firms. The success of East Asian countries in encouraging investment from both domestic and foreign firms implies that firms interpret governments’ actions as credible signals of their intention to honor their commitments to firms, consistent with the behavioral theory of commitment.

The Comparative Politics of Corruption: Accounting for the East Asian Paradox in Empirical Studies of Corruption, Growth and Investment

Numerous empirical studies demonstrate that corruption reduces investment and/or slows growth. But how robust are these relationships? This question is answered by conducting a series of crosscountry regression tests using four different corruption datasets. We find that corruption slows growth and/or reduces investment in most developing countries, particularly small developing countries, but increases growth in the large East Asian newly industrializing economies. The latter finding provides solid empirical support to a country case literature that explains the East Asian paradox––the combination of high corruption and high growth––in terms of stable and mutually beneficial exchanges of government promotional privileges for bribes and kickbacks.