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 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.

Prognostic effect of mean platelet volume in patients with coronary artery disease

2015 ◽  
Vol 114 (12) ◽  
pp. 1299-1309 ◽  
Author(s):  
Nakarin Sansanayudh ◽  
Dittapol Muntham ◽  
Sukit Yamwong ◽  
Mark McEvoy ◽  
John Attia ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Prognostic Marker ◽  
Mean Platelet Volume ◽  
Cardiovascular Events ◽  
Platelet Reactivity ◽  
Mean Difference ◽  
Blood Collection ◽  
Platelet Volume ◽  
Artery Disease

SummaryLarge platelets with high haemostatic activity may lead to increased platelet aggregation.. Mean platelet volume (MPV), an indicator of platelet reactivity, may emerge as a prognostic marker in patients with coronary artery disease (CAD). It was the objective of this study to conduct a systematic review and meta-analysis to assess prognostic effects of MPV on cardiovascular events (CVE) in CAD patients. We searched MEDLINE and SCOPUS from inception to January 2, 2014. All studies that reported MPV and the incidence of cardiovascular events in CAD patients were included. Two reviewers independently extracted the data. A random-effects model was applied for pooling the mean difference of MPV between patients with vs without CVE. Among 30 eligible studies, eight studies reported mean difference of MPV between CVE groups, 11 studies reported MPV dichotomous into high vs low MPV groups, and 11 studies reported both. The pooled mean difference was 0.69 fL (95 %CI = 0.36, 1.01), i. e. patients with CVE had a MPV about 0.69 fL higher than non-CVE. Patients with higher MPV were about 12 % more likely to die than patients with lower MPV (RR 1.12; 95 %CI = 1.02–1.24). However, pooling these effects was based on high heterogeneity and the source of heterogeneity could not be identified. This might be explained by many differences among included studies (e. g. study population, outcomes of interest, analysate, time between blood collection and MPV analysis, etc). These findings suggest that MPV may be a useful prognostic marker in patients with CAD.

scholarly journals The effect of CYP2C19 gene polymorphisms on the pharmacokinetics and pharmacodynamics of prasugrel 5-mg, prasugrel 10-mg and clopidogrel 75-mg in patients with coronary artery disease

2014 ◽  
Vol 112 (09) ◽  
pp. 589-597 ◽  
Author(s):  
Thomas Bergmeijer ◽  
Udaya Tantry ◽  
Jurrien ten Berg ◽  
Dominick Angiolillo ◽  
Stefan James ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Active Metabolite ◽  
Light Transmission ◽  
Platelet Reactivity ◽  
Stable Coronary Artery Disease ◽  
Geometric Mean ◽  
Reactivity Index ◽  
Cyp2c19 Genotype ◽  
Artery Disease

Summary CYP2C19 genotype has been shown to impact response to clopidogrel 75-mg but not prasugrel 10-mg. Here, we assessed effects of CYP2C19 metaboliser status on pharmacokinetics (PK) and pharmacodynamic (PD) responses to prasugrel 5-mg and 10-mg and clopidogrel 75-mg using data from two PK/PD studies in stable coronary artery disease (CAD) patients (GENERATIONS and FEATHER). Active metabolite concentrations (area under the curve, AUC[0-tlast]), maximum platelet aggregation (MPA) measured by light transmission aggregometry, vasodilator- stimulated phosphoprotein platelet reactivity index, and VerifyNow P2Y12-platelet reaction units (VN-PRU) were analysed by CYP2C19-predicted phenotype (extensive metaboliser [EM; N=154], *2-*8 non-carriers, vs reduced metaboliser [RM; N=41],*2-*8 carriers/* 17 non-carriers). AUC(0-tlast) was unaffected by metaboliser status for prasugrel 5-mg and 10-mg (geometric mean EM/RM ratios 1.00, 95% confidence interval [CI]: 0.86,1.17, p>0.99; and 0.97, 95% CI:0.85,1.12, p=0.71, respectively), but was lower among RMs receiving clopidogrel 75-mg (1.37, 95% CI:1.14,1.65, p<0.001). Platelet reactivity was not significantly affected by CYP2C19 metaboliser status for prasugrel 5-mg, or for prasugrel 10-mg by MPA and VNPRU, but for clopidogrel 75-mg was significantly higher in reduced metabolisers (all measures p<0.01). Prasugrel 10-mg showed greater antiplatelet effects vs clopidogrel 75-mg (all comparisons p<0.001). Prasugrel 5-mg showed greater antiplatelet effects vs clopidogrel 75-mg in RMs (all p<0.001), and comparable effects in EMs (all p≥0.37). In contrast to clopidogrel, prasugrel active metabolite PK was not influenced by CYP2C19 genotype. Antiplatelet effect for prasugrel 10-mg was greater irrespective of metaboliser status and for prasugrel 5-mg was greater for RMs and comparable for EMs as compared to clopidogrel 75-mg.

Diabetes mellitus, CYP2C19 genotype, and response to escalating doses of clopidogrel

2016 ◽  
Vol 116 (07) ◽  
pp. 69-77 ◽  
Author(s):  
Edward Carreras ◽  
Willibald Hochholzer ◽  
Andrew Frelinger ◽  
Francesco Nordio ◽  
Michelle O’Donoghue ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Maintenance Dose ◽  
Platelet Reactivity ◽  
Fold Increase ◽  
Cyp2c19 Genotype ◽  
Artery Disease

SummaryBoth diabetes mellitus (DM) and carriage of the CYP2C19*2 allele are associated with a reduced response to clopidogrel. The relative contributions of these factors and whether higher clopidogrel doses can overcome both factors remain unknown. The objective of this study was to test the ability of clopidogrel doses up to 300 mg daily to decrease platelet reactivity in patients with DM and/or CYP2C19*2. ELEVATE-TIMI 56 randomised 333 patients with coronary artery disease to different maintenance doses of clopidogrel in four treatment periods, each lasting approximately 14 days. On-treatment platelet reactivity was compared between patients stratified by DM, CYP2C19*2 status and clopidogrel dose. Both DM and CYP2C19*2 were independently associated with elevated on-treatment platelet reactivity with clopidogrel 75 mg daily (p<0.0001 for each). With 75 mg, mean on-treatment PRU was progressively higher (p trend <0.001) when evaluating patients: with neither DM nor CYP2C19*2 (150.7; 95 % CI 140.5–162.6), with only DM (187.2; 95 % CI, 171.3–206.9), with only CYP2C19*2 (227.9; 95 % CI, 205.1–250.8), and with both DM and CYP2C19*2 (239.9; 95 % CI, 209.7–270.1). Notably, with 75 mg, patients with only CYP2C19*2 had higher ontreatment platelet reactivity than those with only DM (p=0.0068). To achieve on-treatment platelet reactivity similar to that seen with clopidogrel 75 mg in patients with neither DM nor CYP2C19*2, the following doses were required: 150 mg with only DM, 225 mg with only CYP2C19*2, and 300 mg with both DM and CYP2C19*2. Patients with both DM and CYP2C19*2 required a four-fold increase in clopidogrel maintenance dose as compared to patients without these factors to achieve a similar antiplatelet response.

scholarly journals Impact of rheumatoid arthritis on major cardiovascular events in patients with and without coronary artery disease

2020 ◽  
Vol 79 (9) ◽  
pp. 1182-1188 ◽  
Author(s):  
Brian Bridal Løgstrup ◽  
Kevin Kris Warnakula Olesen ◽  
Dzenan Masic ◽  
Christine Gyldenkerne ◽  
Pernille Gro Thrane ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cardiovascular Events ◽  
Treatment Strategies ◽  
Population Based ◽  
Major Adverse Cardiovascular Events ◽  
All Cause Mortality ◽  
Artery Disease ◽  
The Impact

IntroductionRheumatoid arthritis (RA) is a risk factor for cardiovascular disease. The clinical consequences of coincident RA and coronary artery disease (CAD) are unknown.ObjectiveWe aimed to estimate the impact of RA on the risk of adverse cardiovascular events in patients with and without CAD.MethodsA population-based cohort of patients registered in the Western Denmark Heart Registry, who underwent coronary angiography (CAG) between 2003 and 2016, was stratified according to the presence of RA and CAD. Endpoints were myocardial infarction (MI), major adverse cardiovascular events (MACE; MI, ischaemic stroke and cardiac death) and all-cause mortality.ResultsA total of 125 331 patients were included (RA: n=1732). Median follow-up was 5.2 years. Using patients with neither RA nor CAD as reference (cumulative MI incidence 2.7%), the 10-year risk of MI was increased for patients with RA alone (3.8%; adjusted incidence rate ratio (IRRadj) 1.63, 95% CI 1.04 to 2.54), for patients with CAD alone (9.9%; IRRadj 3.35, 95% CI 3.10 to 3.62), and highest for patients with both RA and CAD (12.2%; IRRadj 4.53, 95% CI 3.66 to 5.59). Similar associations were observed for MACE an all-cause mortality.ConclusionsIn patients undergoing CAG, RA is significantly associated with the 10-year risk of MI, MACE and all-cause mortality regardless of the presence of CAD. However, patients with RA and CAD carry the largest risk, while the additive risk of RA in patients without CAD is minor. Among patients with RA, risk stratification by presence or absence of documented CAD may allow for screening and personalised treatment strategies

Body mass index, silent coronary artery disease and the impact of adopting healthy lifestyle and sexual performance on the risk of major adverse cardiovascular events in erectile dysfunction patients

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Ioakeimidis ◽  
D Terentes-Printzios ◽  
A Angelis ◽  
C Georgakopoulos ◽  
V Gardikioti ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cardiovascular Events ◽  
Stress Echocardiography ◽  
Healthy Lifestyle ◽  
Sexual Life ◽  
Major Adverse Cardiovascular Events ◽  
Artery Disease ◽  
The Impact

Abstract Background Erectile dysfunction (ED) is associated with a higher prevalence of risk factors such as hypertension and diabetes and it is an independent predictor of major adverse cardiovascular events (MACE). ED is a common problem in men with obesity. Purpose The aim of this study is to investigate the association of overweight and obesity with asymptomatic coronary artery disease and the impact of lifestyle interventions on MACE risk in men suffering from ED. Methods A total of 614 patients (55±9 y/o) with ED and without known cardiovascular disease (CVD) underwent dobutamine stress echocardiography (and coronary angiography in patients with positive stress echocardiography for myocardial ischemia) to reveal occult coronary artery disease (CAD). In all patients C-reactive protein (CRP) and total testosterone (TT) were measured at entry. After this evaluation and management of concomitant traditional risk factors they were advised to adopt the recommended strategies for healthy lifestyle and improvement of sexual activity. Results The whole population was divided into three groups according to body mass index (BMI) at entry (normal: 18–25.5 kg/m2, n=132; overweight:25.5–29.9 kg/m2, n=295; and obesity: &gt;29.9kg/m2, n=187). There were no statistically significant differences in age, blood pressure (BP) level and smoking prevalence between the three groups. Obese ED patients had significantly lower TT and higher CRP compared to overweight and normal BMI patients (overall P&lt;0.001 and P&lt;0.01, respectively). The prevalence of angiographically documented CAD was not different between obese and overweight patients and it was significantly higher compared to that of subjects with normal BMI (13.8% vs 14.5% vs 7.2%, respectively, overall P&lt;0.05). In the whole study population, a total of 43 (7%) MACE occurred during a mean follow-up of 6.7 years after adopting a healthy lifestyle and improvement in sexual life. Interestingly, overweight status at baseline was associated with a higher MACE prevalence and the overall difference between the three BMI groups at entry was statistically significant (Mantel log-rank test: 8.65; P=0.0014) (Figure 1). Furthermore, in a Cox proportional hazard model overweight at entry (3.14, CI: 1.49–7.87, P&lt;0.01), TT level (0.72; CI 0.56–0.97, P&lt;0.01) and the use of phosphodiesterase-5 (PDE-5) inhibitors (0.83; CI 0.67–0.97, P&lt;0.05) were independent predictors of MACE. Conclusion Overweight and obese ED patients have similar prevalence of asymptomatic CAD, however the overweight profile at baseline appears to have a significantly higher MACE risk compared to obesity at follow-up after adopting a healthy lifestyle and improving sexual life with PDE-5 inhibitors. The paradox finding warrants further investigation. Figure 1. BMI categories and MACE risk Funding Acknowledgement Type of funding source: None

Serum FGF-21 Is Associated with Future Cardiovascular Events in Patients with Coronary Artery Disease—Results from a Median Follow-Up of 4.8 Years Study

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 426-P
Author(s):  
YUQIAN BAO ◽  
YUN SHEN ◽  
XUELI ZHANG ◽  
YITING XU ◽  
QIN XIONG ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cardiovascular Events ◽  
Artery Disease
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