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Current Antiplatelet Treatment Strategy in Patients with Diabetes Mellitus
정정화,Udaya S. Tantry,Paul A. Gurbel,정영훈 대한당뇨병학회 2015 Diabetes and Metabolism Journal Vol.39 No.2
Patients with diabetes mellitus (DM) have accelerated atherosclerosis with an increased risk for atherothrombotic cardiovascular complications. A state of high platelet reactivity and activation, hypercoagulability (prothrombotic state) and a subdued response to standard antiplatelet agents may explain high rate of adverse cardiovascular events in patients with DM. Several antithrombotic treatment strategies have been developed to control the prothrombotic state in patients with DM: dose modification of commonly used agents; use of potent agents; and addition of a third antithrombotic drug (triple therapy) to commonly prescribed dual antiplatelet therapy of aspirin and a P2Y12 inhibitor. The present review aims to provide an overview of the current knowledge on platelet abnormalities in patients with DM, focusing on the challenges and perspectives of antiplatelet treatment strategies in this population.
Hyun Kuk Kim,Udaya S. Tantry,Hyun Woong Park,Eun-Seok Shin,Tobias Geisler,Diana A. Gorog,Paul A. Gurbel,Young-Hoon Jeong 대한심장학회 2021 Korean Circulation Journal Vol.51 No.3
Arterial and venous atherothrombotic events are finely regulated processes involving a complex interplay between vulnerable blood, vulnerable vessel, and blood stasis. Vulnerable blood (‘thrombogenicity’) comprises complex interactions between cellular components and plasma factors (inflammatory, procoagulant, anticoagulant, and fibrinolytic factors). The extent of thrombogenicity may determine the progression of atheroma and the clinical manifestation of atherothrombotic events, with the highest thrombogenicity in African Americans and lowest in East Asians. Inherent thrombogenicity may influence clinical efficacy and safety of specific antithrombotic treatments in high-risk patients, which may in part explain the observation that East Asian patients have reduced anti-ischemic benefits and elevated bleeding risk with antithrombotic therapy compared to Caucasian patients. In this review, we discuss available evidence regarding the racial differences in thrombogenicity and its impact on clinical outcomes among patients with atherosclerotic cardiovascular disease.
Jeong, Young-Hoon,Tantry, Udaya S.,Park, Yongwhi,Kwon, Tae Jung,Park, Jeong Rang,Hwang, Seok-Jae,Bliden, Kevin P.,Koh, Eun-Ha,Kwak, Choong Hwan,Hwang, Jin-Yong,Kim, Sunjoo,Gurbel, Paul A. American Diabetes Association 2012 Diabetes care Vol.35 No.11
<P><B>OBJECTIVE</B></P><P>To determine the effect of adding cilostazol (100 mg b.i.d.) to standard-dose clopidogrel (75 mg/d) (TRIPLE) compared with double-dose clopidogrel (150 mg/d) (DOUBLE) and the influence of the cytochrome P450 (<I>CYP2C19*2/*3</I>, <I>CYP3A5*3)</I>and ATP-binding cassette subfamily B1(<I>ABCB1 C3435T</I>) genetic polymorphisms in type 2 diabetes (T2DM) patients.</P><P><B>RESEARCH DESIGN AND METHODS</B></P><P>T2DM patients were treated with TRIPLE (<I>n</I> = 41) or DOUBLE (<I>n</I> = 39) after percutaneous coronary intervention. Conventional aggregometry and VerifyNow were performed at baseline and at 30 days. The primary end point was absolute change in 20-μM ADP-induced maximal platelet aggregation (ΔMPA<SUB>20</SUB>) between baseline and switching values.</P><P><B>RESULTS</B></P><P>TRIPLE versus DOUBLE showed greater ΔMPA<SUB>20</SUB> (22.9 ± 11.6 vs.12.7 ± 15.5%; difference, 10.2% [95% CI 4.2–16.3]; <I>P</I> < 0.001). Carriage of one (β coefficient, −5.4%; <I>P</I> = 0.162) and two <I>CYP2C19</I> loss-of-function allele(s) (−8.3%; <I>P</I> = 0.007) were associated with lower ΔMPA<SUB>20</SUB> in DOUBLE–treated patients, but not in TRIPLE-treated patients.</P><P><B>CONCLUSIONS</B></P><P>Among T2DM patients, adding cilostazol achieves greater platelet inhibition compared with clopidogrel (150 mg/d), which is not influenced by genetic polymorphisms.</P>
Kwon, Tae Jung,Tantry, Udaya S.,Park, Yongwhi,Choi, Young-Min,Ahn, Jong-Hwa,Kim, Kye Hwan,Koh, Jin-Sin,Park, Jeong-Rang,Hwang, Seok-Jae,Kwak, Choong Hwan,Hwang, Jin-Yong,Gurbel, Paul A.,Smith Jr, Sidn Schatt 2016 Thrombosis and Haemostasis Vol. No.
<B>Summary</B><P>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.</P>