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

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.

Download Full-text

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

Circulation ◽

10.1161/circ.116.suppl_16.ii_76-b ◽

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 (%)

Download Full-text

High-Dose Clopidogrel Loading in Percutaneous Coronary Intervention

Annals of Pharmacotherapy ◽

10.1345/aph.1e463 ◽

2005 ◽

Vol 39 (5) ◽

pp. 918-922 ◽

Cited By ~ 5

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.

Download Full-text

Use of Thromboelastography Platelet Mapping for Assessment of Individual Platelet Response Secondary to Oral Antiplatelet Therapy after Percutaneous Coronary Intervention: An Attempt to Start Personalized Antiplatelet Therapy in India

Journal of Cardiac Critical Care TSS ◽

10.1055/s-0041-1724225 ◽

2021 ◽

Author(s):

Suvro Sankha Datta ◽

Dibyendu De ◽

Nadeem Afroz Muslim

Keyword(s):

Percutaneous Coronary Intervention ◽

Antiplatelet Therapy ◽

Platelet Reactivity ◽

Coronary Intervention ◽

Platelet Inhibition ◽

P Value ◽

Platelet Response ◽

Percutaneous Coronary ◽

The Individual ◽

Platelet Functions

AbstractHigh on-treatment platelet reactivity (HPR) with P2Y12 receptor antagonists in patients treated with dual antiplatelet therapy (DAPT) is strongly associated with adverse ischemic events after percutaneous coronary intervention (PCI). This prospective study was conducted to assess individual platelet response and HPR to antiplatelet medications in post-PCI cases by thromboelastography platelet mapping (TEG-PM). Total 82 patients who were on aspirin and on either clopidogrel, prasugrel, or ticagrelor were evaluated. The percentage of platelet inhibition to arachidonic acid (AA) and adenosine disdiphosphate (ADP) was calculated by [100-{(MA ADP/AA–MA Fibrin) / (MA Thrombin–MA Fibrin) × 100}], taking 50% response as cut-off for HPR. HPR to clopidogrel and prasugrel was 14.29 and 12.5%, respectively. No HPR was detected to aspirin and ticagrelor. The mean percentage of platelet inhibition was significantly higher in patients with ticagrelor 82.99, 95% confidence interval (CI) of [77.3, 88.7] as compared with clopidogrel 72.21, 95% CI of [65.3, 79.1] and prasugrel 64.2, 95% CI of [52.5, 75.9] (p-value of 0.041 and 0.003, respectively). Aspirin along with ticagrelor is associated with a higher mean percentage of platelet inhibition, and lower HPR as compared with the usage of aspirin combined with clopidogrel or prasugrel. Additionally, it might also be concluded that TEG-PM could be used effectively to measure the individual platelet functions which would make oral antiplatelet therapy more personalized for cardiac patients.

Download Full-text

Clopidogrel pretreatment in primary percutaneous coronary intervention: Prevalence of high on-treatment platelet reactivity and impact on preprocedural patency of the infarct-related artery

Thrombosis and Haemostasis ◽

10.1160/th13-01-0057 ◽

2013 ◽

Vol 110 (07) ◽

pp. 110-117 ◽

Cited By ~ 15

Author(s):

Javier Berdejo ◽

Gerard Roura ◽

Josep Gómez-Lara ◽

Rafael Romaguera ◽

Luis Teruel ◽

...

Keyword(s):

Percutaneous Coronary Intervention ◽

Primary Percutaneous Coronary Intervention ◽

Light Transmission ◽

Platelet Reactivity ◽

Poor Response ◽

Antiplatelet Agents ◽

Coronary Intervention ◽

Platelet Inhibition ◽

Percutaneous Coronary ◽

Infarct Related Artery

SummaryTo date, there is limited data on levels of platelet inhibition achieved in patients with ST-elevation myocardial infarction (STEMI) who are loaded with clopidogrel and aspirin (ASA) prior to undergoing primary percutaneous coronary intervention (P-PCI). The aim of this investigation was to evaluate the percentage of STEMI patients with high on-treatment platelet reactivity (HPR) to clopidogrel at the time of initiating P-PCI and its association with the initial patency of the infarct-related artery (IRA). This prospective pharmacodynamic study included 50 STEMI patients, previously naïve to oral antiplatelet agents, who received 500-mg ASA and 600-mg clopidogrel loading doses prior to P-PCI. Platelet function assessment was performed at the beginning of the procedure using various assays, including VerifyNow™ system (primary endpoint), light transmission aggregometry and multiple electrode aggregometry. The percentage of patients with suboptimal response to clopidogrel and ASA assessed with the VerifyNow™ system was 88.0% and 28.6%, respectively. Similar results were obtained with the other assays used. A higher percentage of patients with initial patency of the IRA was observed among those patients without HPR compared with those with HPR to clopidogrel (66.7% vs 15.9%; p=0.013), while no differences were observed regarding postprocedural angiographic or electrocardiographic outcomes. In conclusion, this study shows that a high percentage of STEMI patients have inadequate levels of clopidogrel-induced and, to a lesser extent, aspirin-mediated platelet inhibition when starting a P-PCI procedure, and suggests that a poor response to clopidogrel might be associated with impaired initial TIMI flow in the IRA.

Download Full-text

Comparison of P2Y12 receptor inhibition by clopidogrel and prasugrel in patients undergoing percutaneous coronary intervention

Bangladesh Medical Research Council Bulletin ◽

10.3329/bmrcb.v39i3.20315 ◽

2014 ◽

Vol 39 (3) ◽

pp. 139-145 ◽

Cited By ~ 2

Author(s):

MM Haq ◽

CH Ahsan ◽

MN Amin ◽

MR Karim ◽

ML Ali ◽

...

Keyword(s):

Percutaneous Coronary Intervention ◽

Light Transmission ◽

Coronary Intervention ◽

Platelet Inhibition ◽

Antiplatelet Drug ◽

Platelet Surface ◽

Federal Drug Administration ◽

Coronary Syndrome ◽

Percutaneous Coronary ◽

Verify Now

Dual antiplatelet treatment (DAPT) with aspirin and clopidogrel is vital after percutaneous coronary intervention (PCI). Clopidogrel and prasugrel act on P2Y12 platelet surface receptors. Both these P2Y12 inhibitors are pro-drugs and depend on cytochrome system of the liver for their conversion to active metabolite. There is growing concern regarding suboptimal response in platelet inhibition by clopidogrel. Verify Now system got approval by Federal Drug Administration, USA, for assessing platelet function as its result is almost comparable to gold standard Light Transmission Aggregometry (LTA). There are no data on the prevalence of clopidogrel resistance in Bangladeshi population. Prasugrel, as an antiplatelet drug, is a newer introduction in this country. This study will show light on the efficacy of these drugs on our population especially in patients who undergo PCI where DAPT is mandatory. A total 120 (60 diabetics ) patients with Acute Coronary Syndrome (ACS), were alternatively given 600 mg clopidogrel loading dose (LD) followed by 75 mg maintenance dose (MD) daily or 60 mg LD of prasugrel followed by 10 mg MD daily. Five samples of blood were taken at different time intervals over a period of 2 weeks. Measurement of percent inhibition of P2Y12 was done by VerifyNow. Patients who showed less than 20% inhibition (clopidogrel resistant) at any stage were switched to prasugrel. The outcomes of clopidogrel, prasugrel and clopidogrel switched to prasugrel groups were then compared. Nearly half (46.7%) of the patients in the clopidogrel group was found resistant to the drug as opposed to none in the prasugrel group. No difference was found between diabetic and non-diabetic subjects with respect to drug resistance. Intracoronary blood samples showed high degree of platelet inhibition with prasugrel. There was a gradual decline of platelet inhibition over two weeks with prasugrel. Almost fifty percent of the population is clopidogrel resistant in our study. Prasugrel is a much more potent antiplatelet drug and should be preferred in patients undergoing PCI. Prasugrel may also show resistance over time. DOI: http://dx.doi.org/10.3329/bmrcb.v39i3.20315 Bangladesh Med Res Counc Bull 2013; 39: 139-145

Download Full-text