scholarly journals CYP2C19 Genotype, Clopidogrel Metabolism, Platelet Function, and Cardiovascular Events

JAMA ◽  
2011 ◽  
Vol 306 (24) ◽  
pp. 2704 ◽  
Author(s):  
Michael V. Holmes ◽  
Pablo Perel ◽  
Tina Shah ◽  
Aroon D. Hingorani ◽  
Juan P. Casas
Keyword(s):  
Platelet Function ◽  
Cardiovascular Events ◽  
Cyp2c19 Genotype

The platelet P2Y12 receptor for adenosine diphosphate: congenital and drug-induced defects

Blood ◽  
2011 ◽  
Vol 117 (7) ◽  
pp. 2102-2112 ◽  
Author(s):  
Marco Cattaneo
Keyword(s):  
Platelet Function ◽  
Cardiovascular Events ◽  
Thrombus Formation ◽  
Adenosine Diphosphate ◽  
New Drugs ◽  
Drug Induced ◽  
P2y12 Inhibitors ◽  
Major Cardiovascular Events ◽  
Platelet Receptor ◽  
Net Clinical Benefit

Abstract P2Y12, the Gi-coupled platelet receptor for adenosine diphosphate (ADP), plays a central role in platelet function. Patients with congenital P2Y12 defects display a mild to moderate bleeding diathesis, characterized by mucocutaneous bleedings and excessive post-surgical and post-traumatic blood loss. Defects of P2Y12 should be suspected when ADP, even at high concentrations (≥ 10μM), is unable to induce full, irreversible platelet aggregation. Tests that evaluate the degree of inhibition of adenylyl cyclase by ADP should be used to confirm the diagnosis. Drugs that inhibit P2Y12 are potent antithrombotic drugs, attesting the central role played by P2Y12 in platelet thrombus formation. Clopidogrel, the most widely used drug that inhibits P2Y12, is effective both in monotherapy and in combination with acetylsalicylic acid. The most important drawback of clopidogrel is its inability to inhibit adequately P2Y12-dependent platelet function in approximately one-third of patients who are therefore not protected from major cardiovascular events. New drugs, such as prasugrel and ticagrelor, which effectively inhibit P2Y12 in the majority of patients, proved to be more efficacious than clopdidogrel in preventing major cardiovascular events. Although they increase the incidence of major bleedings, the net clinical benefit is in favor of the new P2Y12 inhibitors.

scholarly journals The Impact of Cytochrome P450 2C19 Polymorphism on Cardiovascular Events in Indonesian Patients with Coronary Artery Disease

2017 ◽  
pp. 18-24
Author(s):  
Muzakkir Amir ◽  
Mirnawati Mappiare ◽  
Paskalis Indra
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Platelet Aggregation ◽  
Cardiovascular Events ◽  
Cardiovascular Death ◽  
Cyp2c19 Genotype ◽  
Cyp2c19 Polymorphism ◽  
Cytochrome P450 2C19 ◽  
Artery Disease ◽  
The Impact

Background: The polymorphism of cytochrome P450 2C19 (CYP2C19) has been documented as the determinant variability in the antiplatelet effect of clopidogrel. The relation between CYP2C19 polymorphism and the antiplatelet efficacy of clopidogrel in Indonesian patients with coronary artery disease (CAD) is unknown. To address this issue, we examined the distribution of CYP2C19 genotypes and platelet aggregation, and assessed the impact of CYP2C19 polymorphism on response to clopidogrel and cardiovascular events. Methods: This observational analytic study with prospective cohort approach was conducted in Wahidin Sudirohusodo and Hasanuddin University Hospital, Makassar. We measured the CYP2C19 genotype by polymerase chain reaction-restriction fragment linked polymorphism (PCR-RFLP) method and platelet aggregation by optical platelet aggregometry with 10 μmol of adenosine diphosphate (ADP) in 69 patients with stable CAD who were treated with clopidogrel. Platelet hyperaggregation was defined as maximal platelet aggregation > 94.3%. The patients were followed up every month at the outpatient department for 6 months or at end point. The end point was acute myocardial infarction, ischemic stroke, or cardiovascular death. Results: Distribution of CYP2C19 alleles were 89.8%, 40.6%, and 11.6%, in CYP2C19*1, CYP2C19*2, and CYP2C19*3, respectively. Distribution of CYP2C19 genotype were 50.7%, 29.0%, 8.7%, 8.7%, and 2.9% in CYP2C19*1/*1, *1/*2, *1/*3, *2/*2, and *2/*3, respectively. Platelet hyper aggregation was more in patients with polymorphism than wild type (p 0.034; OR 3.707) and was associated with cardiovascular events (p 0.030; OR 13.250). There was acute myocardial infarction in 2 patients, ischemic stroke in 1 patient, and cardiovascular death in 1 patient. All of these patients were carrying at least one variant allele of CYP2C19; details of genotype were in two patients with CYP2C19*1/*2, one patient with *2/*2, and one with *2/*3 alleles. Conclusion: CYP2C19*2 and *3 were associated with cardiovascular events due to platelet hyper aggregation.

Serum Concentration of Growth Differentiation Factor-15 Is Independently Associated with Global Platelet Function and Higher Fibrinogen Values in Adult Healthy Subjects

2017 ◽  
Vol 43 (06) ◽  
pp. 621-628 ◽  
Author(s):  
Gian Salvagno ◽  
Elisa Danese ◽  
Giorgio Brocco ◽  
Matteo Gelati ◽  
Martina Montagnana ◽  
...  
Keyword(s):  
Renal Function ◽  
Serum Concentration ◽  
Platelet Function ◽  
Healthy Subjects ◽  
Cardiovascular Events ◽  
Linear Regression Analysis ◽  
Univariate Analysis ◽  
Plasma Fibrinogen ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor

AbstractGrowth differentiation factor-15 (GDF-15) has recently emerged as a strong and independent predictor of cardiovascular events and mortality. However, the pathophysiological mechanisms underlying this important association remain speculative. This study was aimed to investigate the potential associations between the serum concentration of GDF-15 and clinical or laboratory parameters in a population of ostensibly healthy subjects. The study population consisted of 44 healthy volunteers enrolled from the laboratory staff (14 males and 30 females; mean age, 47 ± 11 years), who had their blood collected for assessing complete blood cell count, GDF-15, serum creatinine, albumin, cardiac troponin T, galectin-3, routine coagulation tests, D-dimer, von Willebrand factor, and platelet function testing using platelet function analyzer-100. In univariate analysis, serum GDF-15 was found to be positively associated with age and plasma fibrinogen, and negatively associated with renal function and collagen-epinephrine (CEPI). In multiple linear regression analysis, serum GDF-15 remained significantly associated with renal function, CEPI, and plasma fibrinogen. Healthy subjects with GDF-15 above the median value had a twofold probability of displaying shorter CEPI closure times. Taken together, these results suggest that higher serum values of GDF-15 may be associated with overall global platelet hyperactivity and increased plasma fibrinogen, so providing another plausible explanation for the association between GDF-15, cardiovascular events, and mortality.

Effect of Vonoprazan on the Anti-Platelet Function of Clopidogrel or Prasugrel in Relation to CYP2C19 Genotype

2017 ◽  
Vol 152 (5) ◽  
pp. S150-S151
Author(s):  
Takuma Kagami ◽  
Mihoko Yamade ◽  
Hitomi Ichikawa ◽  
Takahiro Uotani ◽  
Shu Sahara ◽  
...  
Keyword(s):  
Platelet Function ◽  
Cyp2c19 Genotype

The impact of CYP2C19 genotype on cardiovascular events and platelet reactivity in patients with coronary artery disease receiving clopidogrel

2013 ◽  
Vol 168 (2) ◽  
pp. 1594-1596 ◽  
Author(s):  
Dimitris Tousoulis ◽  
Gerasimos Siasos ◽  
Marina Zaromitidou ◽  
Evangelos Oikonomou ◽  
Konstantinos Maniatis ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cardiovascular Events ◽  
Platelet Reactivity ◽  
Cyp2c19 Genotype ◽  
Artery Disease ◽  
The Impact

scholarly journals Aspirin Exposure Reveals Novel Genes Associated With Platelet Function and Cardiovascular Events

2013 ◽  
Vol 62 (14) ◽  
pp. 1267-1276 ◽  
Author(s):  
Deepak Voora ◽  
Derek Cyr ◽  
Joseph Lucas ◽  
Jen-Tsan Chi ◽  
Jennifer Dungan ◽  
...  
Keyword(s):  
Platelet Function ◽  
Cardiovascular Events ◽  
Novel Genes

scholarly journals Diabetes mellitus, platelet function and acetylsalicylic acid

2021 ◽  
Vol 17 (3) ◽  
pp. 250-257
Author(s):  
G.F. Gendeleka ◽  
A.N. Gendeleka
Keyword(s):  
Diabetes Mellitus ◽  
Primary Prevention ◽  
Acetylsalicylic Acid ◽  
Platelet Function ◽  
Cardiovascular Events ◽  
Coronary Calcification ◽  
Aspirin Resistance ◽  
Diabetic Patients ◽  
Low Grade ◽  
Level Of Evidence

Diabetes mellitus is an independent risk factor for cardiovascular disease (CVD). Accelerated development of atherosclerosis in patients with diabetes is a consequence of endothelial dysfunction, low-grade inflammation, oxidative stress, dyslipidemia, and platelet dysfunction. The results of studies have shown that among diabetic patients there is a high percentage of no effect when using both acetylsalicylic acid (ASA) and clopidogrel. It is necessary to distinguish between patients with a weak response and people with no effect — resistant to aspirin. The frequency of the so-called aspirin resistance, according to modern research, is different and depends on the methods used to study platelet function. In diabetic patients, it ranges from 5 to 45 % when taking ASA and from 4 to 30 % when taking clopidogrel. Recent studies show an even higher proportion of such individuals among people with diabetes. The appropriateness of lifelong ASA for secondary prevention in people diagnosed with CVD is indisputable (level of evidence A). At the same time, approaches to primary prevention vary in different countries. It is emphasized that the primary prevention with ASA in modern conditions maintains a favorable balance of benefits/risks. The new guidelines state that the calculated 10-year risk of cardiovascular events should not be considered when deciding whether to prescribe ASA to patients without CVD. Instead, all risk factors present in each patient should be considered, including burdensome family history, inability to achieve lipid and glycemic levels, and coronary calcification. The conclusion that ASA has evidence-based efficacy in secondary prophylaxis in patients with CVD has been confirmed. Regarding the primary prevention of cardiovascular events, including healthy individuals, the appropriateness, duration of administration, and choice of ASA should be determined taking into account the 10-year development of serious events, the presence of comorbidities, and the risk of bleeding.

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