C0413: Comparison of Platelet Aggregation Before & After Loading Dose of Prasugrel and Clopidogrel in Percutaneous Coronary Intervention in Adult Pakistani CAD Patients

2014 ◽  
Vol 133 ◽  
pp. S43
Author(s):  
A. Nouman ◽  
A. Shahbaz ◽  
K. Mehdi ◽  
M. Azhar
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Platelet Aggregation ◽  
Coronary Intervention ◽  
Loading Dose ◽  
Percutaneous Coronary

Abstract 4017: Reduced Anti-Platelet Response to Clopidogrel in Diabetic Patients Undergoing Percutaneous Coronary Intervention

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Jorge Saucedo ◽  
Anand Singla ◽  
Karin Mauer ◽  
Kevin P Bliden ◽  
Mark J Antonino ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Platelet Aggregation ◽  
Light Transmission ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
Aspirin Resistance ◽  
Diabetic Patients ◽  
Loading Dose ◽  
Platelet Response ◽  
Percutaneous Coronary

Despite dual antiplatelet therapy with aspirin and clopidogrel, patients with diabetes mellitus (DM) suffer from frequent recurrent ischemic events. Previous studies have shown that DM patients have a higher prevalence of aspirin resistance than non-DM patients. The aim of this analysis was to determine if DM patients have a decreased antiplatelet response to either maintenance or high loading clopidogrel administration when compared to non-DM patients. One hundred and thirty eight patients that underwent percutaneous coronary intervention (PCI) in the Clear Platelets-2 Study were included in this analysis. Patients were grouped according to clopidogrel dose use and presence of DM. Subjects were either on maintenance therapy with 75mg of clopidogrel (C75 group; n=72) or received a loading dose of 600mg of clopidogrel immediately after PCI (C600 group; n=66). All patients received 325-mg aspirin. Platelet function was measured by Light Transmission Aggregometry using ADP (5 and 20μM), TRAP (15 μM), and collagen (2μg/ml). Overall, DM patients in the C75 group had higher platelet aggregation using 5 and 20μM ADP and 2μg/ml collagen. DM patients had lower relative platelet inhibition at 24hrs with 5 μM ADP and 2μg/ml collagen in the C600 group when compared to non-DM patients (Table ). DM patients undergoing PCI exhibit higher platelet aggregation when receiving standard clopidogrel maintenance dose and lower relative platelet inhibition with high clopidogrel loading dose. Higher doses of clopidogrel or more potent P2Y12 receptor antagonists may be needed in DM patients to obtain comparable platelet inhibition to non-DM patients.

Abstract 455: Peri-interventional Antiplatelet Effect of Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention is Attenuated by Cytochrome P450 2C19*2 Polymorphism

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Dietmar Trenk ◽  
Willibald Hochholzer ◽  
Herz-Zentrum Bad Krozingen ◽  
Martin F Fromm ◽  
Ligia Chialda ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Cytochrome P450 ◽  
Platelet Aggregation ◽  
Coronary Intervention ◽  
Loading Dose ◽  
Cyp2c19 Genotype ◽  
Platelet Response ◽  
Antiplatelet Effect ◽  
Percutaneous Coronary ◽  
The Impact

The thienopyridine derivative clopidogrel is an inactive pro-drug requiring biotransformation by cytochrome P450 isoenzymes (CYP) in order to generate an active metabolite. This metabolite inhibits irreversibly the platelet P2Y12 receptor, thereby exerting the antiplatelet effect of the drug. The EXCELSIOR study showed a 7-fold 30-day risk of major adverse cardiac events in patients with inadequate peri-interventional platelet response to loading with clopidogrel 600 mg. Studies in healthy volunteers on the impact of the CYP2C19 genotype to the interindividual variability in antiplatelet effect of clopidogrel showed conflicting results. The EXCELSIOR study enrolled 802 patients undergoing elective percutaneous coronary intervention (PCI) with stent implantation. The antiplatelet effect of a loading dose of clopidogrel 600 mg was determined by optical aggregometry (5μM ADP) before administration of clopidogrel, at the time of PCI and pre-discharge at day 1after PCI. CYP2C19 genotype (681G>A) was analyzed in 697 patients by real-time PCR. Antiplatelet efficacy of clopidogrel was determined for the different genotypes. Within the subset of the EXCELSIOR cohort, 485 patients (69.6%) were CYP2C19 wild-type homozygous (*1/*1), 199 (28.6%) were CYP2C19*1/*2 and 13 (1.9%) were CYP2C19*2/*2 carrying two allelic variants encoding a deficient CYP2C19 enzyme. Residual platelet aggregation (median; interquartile ranges) determined 5 minutes after addition of ADP 5μM is summarized in relation to the CYP2C19 genotypes in the Table below. These results indicate that the antiplatelet response to a loading dose of clopidogrel 600 mg is substantially attenuated in patients carrying at least one CYP2C19*2 allele. It seems that the CYP2C19 genotype is a major factor contributing to the observed variability in the antiplatelet effect of clopidogrel and might therefore affect clinical outcome of patients undergoing PCI. Relationship Between Genotype and ADP-induced Platelet Aggregation (%)

High-Dose Clopidogrel Loading in Percutaneous Coronary Intervention

2005 ◽  
Vol 39 (5) ◽  
pp. 918-922 ◽  
Author(s):  
Kristen L Longstreth ◽  
James R Wertz
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Coronary Intervention ◽  
Drug Manufacturer ◽  
Platelet Inhibition ◽  
High Dose ◽  
Loading Dose ◽  
Percutaneous Coronary ◽  
Safety Studies ◽  
Risk Patients ◽  
Time Required

OBJECTIVE: To review the use of a 600-mg clopidogrel loading dose in patients undergoing percutaneous coronary intervention (PCI). DATA SOURCES: Human clinical trials and platelet studies available through PubMed (1966–March 2005), bibliographies of pertinent articles, and citations supplied by the drug manufacturer were accessed. DATA SYNTHESIS: The administration of a 600-mg loading dose of clopidogrel can decrease the time required for maximum platelet inhibition to 2 hours compared with ⩾6 hours achieved with 300 mg. This higher loading dose has been investigated in multiple platelet studies and one observational report. Several randomized controlled trials have used a 600-mg loading dose; however, these studies were not designed to evaluate the efficacy and safety of this loading regimen. To date, only one randomized trial has compared the 600-mg loading dose with a 300-mg loading dose. CONCLUSIONS: When compared with a conventional loading regimen of 300 mg in lower-risk patients, pretreatment with clopidogrel 600 mg was shown to be more effective in reducing periprocedural events and demonstrated similar safety. Studies are needed to clarify the use of a 600-mg loading dose in higher-risk patients, with concomitant glycoprotein IIb/IIIa receptor antagonism, or when administration is delayed until immediately before or after PCI.

Sign in / Sign up

Export Citation Format

Share Document