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

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

Abstract 4917: Clopidogrel Resistance and Coronary Artery Plaque Burden in Patients Undergoing Percutaneous Coronary Intervention

Circulation ◽

10.1161/circ.118.suppl_18.s_960-a ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Amala Chirumamilla ◽

Akiko Maehara ◽

Gary S Mintz ◽

Roxana Mehran ◽

Adriano Caixeta ◽

...

Keyword(s):

Percutaneous Coronary Intervention ◽

Coronary Intervention ◽

Platelet Inhibition ◽

Smoking History ◽

Plaque Burden ◽

Process Data ◽

Clopidogrel Resistance ◽

Reference Segment ◽

Percutaneous Coronary ◽

Verify Now

Background: Clopidogrel anti-inflammatory effect and plaque burden are important factors for atherothrombotic process. Data are lacking on relationship of plaque burden and clopidogrel resistance in patients undergoing percutaneous coronary intervention (PCI) Methods: We identified 138 patients who had intravascular ultrasound during PCI between Jan 2007 to June 2007. Using the Verify Now Point-of-care assay, P2Y12 platelet reaction units (PRU) and percent inhibition of platelet activation (IPA) were measured 16 –24 hours after the loading dose of clopidogrel (600mg for patients not on clopidogrel daily, and 300mg for patients on clopidogrel 75mg daily) but before the next day of clopidogrel dose. CR was defined as PRU >200 or as IPA<10% or <20%. Results: Mean age of patients was 66±11 years and 74% were males. PRU>200 was found in 53 patients (38.4%) and PRU ≤200 in 85 patients (61.6%). Presence of myocardial infarction, hyperlipidemia, renal disease, smoking history, stable or unstable angina at admission were similar between the PRU groups and between IPA groups. Hypertension, diabetes, older age and reference site plaque burden were higher in clopidogrel resistance (Table ). With use of alternative definitions, reference segment plaque burden was also higher in clopidogrel resistance patients: 0.50±0.12 vs 0.41±0.13 in <10% vs ≥10% platelet inhibition (p=0.05), and 0.49±0.12 vs 0.41±0.13 in <20% vs ≥20% platelet inhibition (p=0.03) Conclusion: Clopidogrel resistance patients have more high risk baseline characteristics and higher plaque burden at the reference vessel segment, implying diffuse intracoronary atherosclerosis compared to clopidogrel sensitive patients who underwent PCI

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

Testing a New Approach for Rapid and Reversible Platelet Inhibition during Percutaneous Coronary Intervention among Patients with Acute Coronary Syndrome

Hospital Practice ◽

10.3810/hp.2010.02.285 ◽

2010 ◽

Vol 38 (1) ◽

pp. 109-111

Author(s):

Kathy L. Lee

Keyword(s):

Percutaneous Coronary Intervention ◽

Acute Coronary Syndrome ◽

Coronary Intervention ◽

Platelet Inhibition ◽

New Approach ◽

Coronary Syndrome ◽

Percutaneous Coronary

Download Full-text

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

Circulation ◽

10.1161/circ.118.suppl_18.s_819-b ◽

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.

Download Full-text

Changes in serum serotonin levels in patients with acute coronary syndrome and stable angina undergoing percutaneous coronary intervention

Journal of International Medical Research ◽

10.1177/0300060520970104 ◽

2020 ◽

Vol 48 (12) ◽

pp. 030006052097010

Author(s):

Donghoon Han ◽

Jae Hyuk Choi ◽

Sehun Kim ◽

Sang Min Park ◽

Dong Geum Shin ◽

...

Keyword(s):

Percutaneous Coronary Intervention ◽

Acute Coronary Syndrome ◽

Stable Angina ◽

Chronic Stable Angina ◽

Antiplatelet Agents ◽

Coronary Intervention ◽

Platelet Inhibition ◽

Coronary Syndrome ◽

Percutaneous Coronary ◽

Serum Serotonin

Objective Activated platelets release serotonin, causing platelet aggregation and vasoconstriction. Serotonin levels were investigated in patients with acute coronary syndrome (ACS) and chronic stable angina (CSA) treated with percutaneous coronary intervention (PCI). Methods Consecutive patients undergoing PCI for either ACS or CSA were enrolled between July 2009 and April 2010. Patients were pre-treated with dual antiplatelet agents (aspirin and clopidogrel) before PCI. Serum serotonin levels, measured at baseline, pre- and post-PCI, and at 90 min, and 6, 12, 24 and 48 h following PCI, were compared between ACS and CSA groups. Results Sixty-three patients with ACS and 60 with CSA were included. Overall baseline characteristics were similar between the two groups. Serotonin levels at post-PCI (55.2 ± 120.0 versus 20.1 ± 24.0) and at peak (regardless of timepoint; 94.0 ± 170.9 versus 38.8 ± 72.3) were significantly higher in the ACS versus CSA group. At 90 min and 6, 24 and 48 h post-PCI, serum serotonin was numerically, but not significantly, higher in patients with ACS. Serotonin levels fluctuated in both groups, showing an initial rise and fall, rebound at 24 h and drop at 48 h post-PCI. Conclusions In patients undergoing PCI, serum serotonin was more elevated in patients with ACS than those with CSA, suggesting the need for more potent and sustained platelet inhibition, particularly in patients with ACS.

Download Full-text

Thrombocytopenia in a Patient Undergoing Primary Percutaneous Coronary Intervention

Folia Medica Indonesiana ◽

10.20473/fmi.v55i1.24434 ◽

2021 ◽

Vol 55 (1) ◽

pp. 68

Author(s):

Yudi Her Oktaviono ◽

Feranti Meuthia

Keyword(s):

Percutaneous Coronary Intervention ◽

Acute Coronary Syndrome ◽

Antiplatelet Therapy ◽

Primary Percutaneous Coronary Intervention ◽

Coronary Intervention ◽

Bare Metal Stent ◽

Antiplatelet Drug ◽

Coronary Syndrome ◽

First Choice ◽

Percutaneous Coronary

Thrombocytopenia is a common abnormality in patients presenting with acute coronary syndrome. Baseline thrombocytopenia in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention is associated with early adverse events, related to both ischemia and bleeding. Treatment for acute coronary syndrome usually involves antiplatelet, anticoagulant, antithrombotic therapy, and the performance of percutaneous coronary intervention. The safety of antiplatelet therapy and percutaneous coronary intervention patients who have acute coronary syndrome and thrombocytopenia is unknown, and there are no guidelines or randomized studies that specifically suggest a treatment approach in such patients. One of the institutions in Italy recommends medical and interventional strategy with radialis as first choice for access site, bare metal stent (BMS) implantation, followed by double antiplatelet therapy (DAPT) for one month. After DAPT discontinuation, at least one antiplatelet drug (aspirin) is recommended for life.

Download Full-text