Publications (2)17.44 Total impact
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Article: Antiplatelet response to the 150-mg maintenance dose of clopidogrel in patients with insufficient platelet inhibition after clopidogrel loading for elective coronary stent placement.
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ABSTRACT: Our prospective study sought to investigate whether inadequate platelet responses to clopidogrel can be corrected by increasing the daily maintenance dose from 75 mg to 150 mg. In 117 patients with elective PCI after loading with 600 mg clopidogrel, we determined residual platelet aggregation in response to 5 micromol/l ADP (RPA) by optical aggregometry after the first 75 mg maintenance dose (baseline), and at days 14 and 28. In patients with RPA >14% at baseline, we increased the daily dose to 150 mg. Fifty-seven additional patients without dose adjustment served as historic control. In 39 patients with baseline RPA >14%, the increase in maintenance dose to 150 mg reduced median RPA significantly (P<0.001) from 24% [interquartile range: 18-32%] at baseline to 14% [8-20%1 at 14 days without any further significant change. In patients with RPA < or = 14%, who continued on 75 mg clopidogrel, RPA increased during the first 14 days by 4.5% (0-14%; P<0.001). At 14 days, the study group with selective dose adjustment had a significantly lower RPA than the control group without dose adjustment (10.0% [4-20%1 versus 17.0% [9-32%], P<0.001). In patients with a low initial response to clopidogrel, platelet inhibition can be improved by increasing the maintenance dose to 150 mg.EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 08/2008; 4(2):214-21. · 3.29 Impact Factor -
Article: Cytochrome P450 2C19 681G>A polymorphism and high on-clopidogrel platelet reactivity associated with adverse 1-year clinical outcome of elective percutaneous coronary intervention with drug-eluting or bare-metal stents.
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ABSTRACT: We investigated whether the loss of function CYP2C19 681G>A *2 polymorphism is associated with high (>14%) residual platelet aggregation (RPA) on clopidogrel and whether high on-clopidogrel RPA impacts clinical outcome after elective coronary stent placement. The cytochrome P450 (CYP)-dependent conversion of clopidogrel to its active metabolite may contribute to the variability in antiplatelet effect of clopidogrel. The study included 797 consecutive patients undergoing percutaneous coronary intervention, who were followed-up for 1 year. Adenosine-diphosphate-induced (5 mumol/l) RPA was assessed after a 600-mg loading dose and after the first 75-mg maintenance dose of clopidogrel before discharge. CYP2C19 genotype was analyzed by real-time polymerase chain reaction. Of the patients included, 552 (69.3%) were CYP2C19 wild-type homozygotes (*1/*1) and 245 (30.7%) carried at least one *2 allele. Residual platelet aggregation at baseline did not differ significantly between genotypes. On clopidogrel, RPA was significantly (p < 0.001) higher in *2 carriers than in wild-type homozygotes (23.0% [interquartile range (IQR) 8.0% to 38.0%] vs. 11.0% [IQR 3.0% to 28.0%] after loading; 11.0% [IQR 5.0% to 22.0%] vs. 7.0% [IQR 3.0% to 14.0%] at pre-discharge). Between *2 carriers and wild-type homozygotes, we found significant (p < 0.001) differences in the proportion of patients with RPA >14%, both after loading (62.4% vs. 43.4%) and at pre-discharge (41.3% vs. 22.5%). Residual platelet aggregation >14% at pre-discharge incurred a 3.0-fold increase (95% confidence interval 1.4 to 6.8; p = 0.004) in the 1-year incidence of death and myocardial infarction. Patients carrying at least one CYP2C19*2 allele are more prone to high-on clopidogrel platelet reactivity, which is associated with poor clinical outcome after coronary stent placement (Effect of Clopidogrel Loading and Risk of PCI [EXCELSIOR]; NCT00457236).Journal of the American College of Cardiology 05/2008; 51(20):1925-34. · 14.16 Impact Factor
