Functional impact of high clopidogrel maintenance dosing in patients undergoing elective percutaneous coronary interventions

2008 ◽  
Vol 99 (01) ◽  
pp. 161-168 ◽  
Author(s):  
Esther Bernardo ◽  
Jorge Palazuelos ◽  
Bhaloo Desai ◽  
Ian Weisberg ◽  
Fernando Alfonso ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Maintenance Dose ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
Relative Increase ◽  
Light Transmittance ◽  
Functional Impact ◽  
Percutaneous Coronary

SummaryThe currently recommended maintenance dose of clopidogrel is often associated with inadequate platelet inhibition, suggesting the need for a higher dose. The aim of this pilot study was to assess the functional impact of a high (150 mg/day) maintenance dose of clopidogrel in patients undergoing elective percutaneous coronary intervention (PCI).This is a prospective, randomized, platelet function study which was performed in elective PCI patients assigned to treatment with either a 75 mg (n=20) or 150 mg (n=20) daily maintenance dose of clopidogrel for 30 days;afterwards, all patients resumed standard dosing. Platelet aggregation was performed using light transmittance aggregometry following 20 μM and 5 μM adenosine diphosphate (ADP) stimuli 30 days after randomization and 30 days after resuming standard dosing. Patients treated with 150 mg/day clopidogrel had lower 20 μMADP-induced platelet aggregation compared to patients on 75 mg/day (52.1±9% vs. 64.0±8%; p<0.001; primary endpoint).The dose-dependent effect was confirmed by the absolute and relative increase in platelet aggregation after resuming standard dosing (p<0.001). No changes were observed in patients randomized to standard dosing. Parallel findings were observed following 5 μM ADP stimuli for all assessments. A broad variability in clopidogrel-induced antiplatelet effects was observed irrespective of dosing. In conclusion, a 150 mg/day maintenance dose regimen of clopidogrel is associated with reduced platelet reactivity and enhanced platelet inhibition compared to that achieved with the currently recommended 75 mg/day in patients undergoing elective PCI.

scholarly journals 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

2021 ◽  
Vol 5 (02) ◽  
pp. 108-113
Author(s):  
Suvro Sankha Datta ◽  
Dibyendu De ◽  
Nadeem Afroz Muslim
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Antiplatelet Therapy ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
P Value ◽  
Platelet Response ◽  
Percutaneous Coronary ◽  
The Individual

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 diphosphate (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.

How Long Does It Take for Clopidogrel and Ticagrelor to Inhibit Platelets in Patients Undergoing Primary Percutaneous Coronary Intervention? A Detailed Pharmacodynamic Analysis: Time Course of Platelet Reactivity in STEMI (TOPS)

2017 ◽  
Vol 43 (04) ◽  
pp. 439-446 ◽  
Author(s):  
Thomas Bergmeijer ◽  
Thea Godschalk ◽  
Paul Janssen ◽  
Kim Berge ◽  
Nicoline Breet ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Antiplatelet Therapy ◽  
Stent Thrombosis ◽  
Primary Percutaneous Coronary Intervention ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
Light Transmittance ◽  
Loading Dose ◽  
Percutaneous Coronary

AbstractAntiplatelet therapy plays a pivotal role in patients with an ST-segment elevation myocardial infarction (STEMI) to prevent further atherothrombotic events, such as stent thrombosis. Although the risk of stent thrombosis is highest in the first hours after primary percutaneous coronary intervention (pPCI), little is known about when an adequate level of platelet inhibition is achieved following a clopidogrel or ticagrelor loading dose in STEMI patients. Patients presenting with STEMI in whom pPCI was performed and who were loaded with 600 mg clopidogrel or 180 mg ticagrelor were eligible for enrolment in this nonrandomized, open label, single-center study. Platelet reactivity was measured before PCI, 6 and 24 hours after loading dose and after 2, 7, and 14 days, using the VerifyNow P2Y12 assay as well as 20 µmol/L adenosine diphosphate stimulated light transmittance aggregometry (LTA). We analyzed the time until a VerifyNow result of < 236 P2Y12 reaction units or LTA maximum platelet aggregation of < 64.5% was reached. A total of 28 patients were participated in this study. Platelet reactivity dropped below the high platelet reactivity cutoff level after 11.4 (VerifyNow) and 5.7 (LTA) hours in patients who were loaded with clopidogrel, and after 2.4 (VerifyNow) and 3.9 (LTA) hours in patients who were loaded with ticagrelor. Despite the administration of a clopidogrel or ticagrelor loading dose, it still takes multiple hours (2–11) to reach adequate platelet inhibition in STEMI patients. This might indicate the need for additional antiplatelet therapy in the first hours after loading in patients undergoing pPCI with stenting.

Antiplatelet efficacy of prasugrel in patients with high on-clopidogrel treatment platelet reactivity and a history of coronary stenting

2013 ◽  
Vol 109 (03) ◽  
pp. 517-254 ◽  
Author(s):  
Isabell Bernlochner ◽  
Katharina Mayer ◽  
Tanja Morath ◽  
Martin Orban ◽  
Stefanie Schulz ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Platelet Aggregation ◽  
Maintenance Dose ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Response Variability ◽  
Clinical Impact ◽  
Percutaneous Coronary ◽  
History Of ◽  
Function Testing

SummaryLittle is known about the antiplatelet action of the 3rd generation thienopyridine prasugrel in patients showing high platelet reactivity (PR) levels on clopidogrel. Thus, we aimed to determine the antiplatelet efficacy of prasugrel loading (LD) and maintenance dose (MD) treatment in a registry of patients with high PR levels on clopidogrel and a consecutive switch over to prasugrel in a setting of routine platelet function testing. In our registry of patients treated by percutaneous coronary intervention (n=73) with high levels of PR on clopidogrel, the ADP-induced platelet aggregation (PA, in AU x min) was assessed on a Multiplate analyser 1) after clopidogrel LD, 2) after prasugrel LD and 3) on prasugrel MD (5 vs. 10 mg/day). In patients with high PR levels on clopidogrel, prasugrel LD resulted in significantly lower PA values (574 [462–698] vs. 156 [89–234] AU x min; p<0.0001). Only 2.7% of patients showed high PR (HPR, 468 AU x min) following prasugrel LD. On prasugrel MD, PA was significantly higher as compared to prasugrel LD (248 [145–406] vs. 156 [89–234] AU x min; p<0.0001) with more patients showing HPR on MD vs. LD (16.4% vs. 2.7%; p=0.009). For prasugrel MD, HPR rates were higher in 5 vs. 10 mg/day treated patients (46.2% vs. 10.0%; p=0.006). In conclusion, for patients with high PR levels on clopidogrel, prasugrel LD abolished this status in the majority of patients. However, prasugrel response variability was detected, being more pronounced on prasugrel MD vs. LD treatment. The clinical impact of these findings warrants further investigation.

scholarly journals 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

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.

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

2013 ◽  
Vol 110 (07) ◽  
pp. 110-117 ◽  
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.

Abstract 3472: The Prediction of Ischemic Events After Percutaneous Coronary Intervention by Platelet Reactivity to Adenosine Diphosphate: First Evidence for an Oral Antiplatelet Therapeutic Target Determined by an Ex Vivo Test of Platelet Function.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Paul Gurbel ◽  
Kevin P Bliden ◽  
Joseph Dichiara ◽  
Mark J Antonino ◽  
Thomas A Suarez ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Risk Factor ◽  
Antiplatelet Therapy ◽  
Therapeutic Target ◽  
Ex Vivo ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Percutaneous Coronary ◽  
Ischemic Events

Background: High on-treatment platelet reactivity to adenosine diphosphate (HPR-ADP) may be a risk factor for ischemic events after percutaneous coronary intervention (PCI). We determined whether a cutpoint of HPR-ADP, similar to the INR used to guide anticoagulant therapy, could predict ischemic event occurrence after PCI. Methods : Post-procedural platelet reactivity to ADP was measured by conventional aggregometry in 352 consecutive patients undergoing non-emergent PCI followed for up to 2 years for post-discharge ischemic events. All patients had received clopidogrel and aspirin therapy at the time of aggregation measurements. Results: Eighty-two patients (23%) suffered ischemic events and had higher 5 and 20 μM ADP-induced aggregation compared to patients without ischemic events (46 ± 14% and 60 ± 13% versus 30 ± 17% and 43 ± 19%, respectively, p<0.0001 for both measurements). Using a combined receiver operator curve analysis, HPR-ADP cutpoints of 46% aggregation following 5μM ADP stimulation and 59% aggregation following 20μM ADP stimulation were associated with 63% and 74% of ischemic events, respectively. Multivariate Cox regression demonstrated significance between events and post-procedural HPR-ADP cutpoints (20μM ADP, OR=8.6, p<0.0001; and 5μM ADP, OR=2.9, p=0.01). Conclusions: High on-treatment platelet reactivity to ADP is an independent risk factor for ischemic events within 2 years of non-emergent PCI. These data are the first to support a therapeutic target for antiplatelet therapy based on an ex vivo platelet function test, similar to the INR used for anticoagulant therapy. The study is a step towards a personalized medicine approach to guide the intensity of antiplatelet therapy.

Abstract 3473: The Effect of Cigarette Smoking on the Antiplatelet Effect of Clopidogrel: The Smokers Paradox

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Paul Gurbel ◽  
Joseph Dichiara ◽  
Kevin P Bliden ◽  
Mark J Antonino ◽  
Lawal Lookman
Keyword(s):  
Platelet Aggregation ◽  
Cigarette Smoking ◽  
Metabolic Activation ◽  
Adenosine Diphosphate ◽  
Platelet Inhibition ◽  
Response Variability ◽  
Light Transmittance ◽  
Prior History ◽  
Platelet Response ◽  
Clopidogrel Therapy

Background: Wide response variability to clopidogrel therapy has been reported. Clopidogrel is a prodrug that requires metabolic activation by hepatic cytochromes (CYP). Cigarette smoking is an inducer of CYP1A2 and may, therefore, enhance the metabolism of clopidogrel. We sought to examine the effect of cigarette smoking on the platelet response to clopidogrel. Methods: Three hundred thirteen consecutive patients undergoing elective coronary stenting were studied. Platelet aggregation (PA) was assessed by light transmittance aggregometry (LTA) stimulated by 5 and 20μ M adenosine diphosphate. One hundred fourteen patients were on chronic clopidogrel therapy, were not reloaded, and had pre-stenting PA measurements. Pre-and post-stenting PA was measured in 199 patients: 60 were loaded with 300mg and 139 were loaded with 600mg. There were 120 current smokers (smoking within 2 weeks of PCI) and 193 non-smokers (no prior history of smoking). Low PA was defined as the lowest two quartiles of 5μM ADP-induced platelet aggregation (≤ 40%). Results: PA was significantly lower (p ≤ 0.008) in smokers on long term chronic clopidogrel treatment (Table ). Relative platelet inhibition (RPI) was higher in smokers treated with either 300mg or 600mg clopidogrel measured by 5 and 20μM ADP-induced PA. In a multivariate analysis, cigarette smoking was an independent predictor of low PA in patients on chronic clopidogrel therapy and in patients loaded with clopidogrel (r=0.3, p=0.0001). Conclusion: Clopidogrel therapy in smokers is associated with increased platelet inhibition and lower aggregation as compared to non-smokers. The mechanism of the smoking effect deserves further study and may be another cause of response variability to clopidogrel. RPI = 100 x ((baseline aggregation-post-treatment aggregation)/(baseline aggregation))

Prasugrel compared with high-dose clopidogrel in acute coronary syndrome

2010 ◽  
Vol 103 (01) ◽  
pp. 213-223 ◽  
Author(s):  
Georgios Sideris ◽  
Remy Cohen ◽  
Catherine Meuleman ◽  
Claire Bal dit Sollier ◽  
Olivier Barthélémy ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Poor Response ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
High Dose ◽  
Coronary Syndrome ◽  
Percutaneous Coronary ◽  
St Elevation ◽  
To Receive

SummaryCompared with the approved dose regimen of clopidogrel (300-mg loading dose [LD], 75-mg maintenance dose [MD]), prasugrel has been demonstrated to reduce ischaemic events in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). In ACS, antiplatelet effects of a prasugrel MD regimen have not been previously compared with either a higher clopidogrel MD or after switching from a higher clopidogrel LD. The objective of this study was to evaluate the antiplatelet effect of a prasugrel 10-mg MD versus a clopidogrel 150-mg MD in patients with ACS who had received a clopidogrel 900-mg LD. Patients with non-ST elevation ACS, treated with aspirin and a clopidogrel 900-mg LD, were randomised within 24 hours post-LD to receive a prasugrel 10-mg or clopidogrel 150-mg MD. After 14 days of the initial MD, subjects switched to the alternative treatment for 14 days. The primary endpoint compared maximum platelet aggregation (MPA, 20 μM adenosine diphosphate [ADP]) between prasugrel and clopidogrel MDs for both periods. Responder analyses between treatments were performed using several platelet-function methods. Of 56 randomised subjects, 37 underwent PCI. MPA was 26.2% for prasugrel 10 mg and 39.1% for clopidogrel 150 mg (p<0.001). The prasugrel MD regimen reduced MPA from the post-900-mg LD level (41.2% to 29.1%, p=0.003). Poor response ranged from 0% to 6% for prasugrel 10 mg and 4% to 34% for clopidogrel 150 mg. Thus, in ACS patients a prasugrel 10-mg MD regimen resulted in significantly greater platelet inhibition than clopidogrel at twice its approved MD or a 900-mg LD.

Sign in / Sign up

Export Citation Format

Share Document