Temporal variability in the antiplatelet effects of clopidogrel and aspirin after elective drug-eluting stent implantation

2015 ◽  
Vol 114 (11) ◽  
pp. 1020-1027 ◽  
Author(s):  
Christian Stratz ◽  
Stefan Leggewie ◽  
Willibald Hochholzer ◽  
Christian M. Valina ◽  
Michael Gick ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Temporal Variability ◽  
Light Transmission ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
Drug Eluting Stent ◽  
Elective Percutaneous Coronary Intervention ◽  
Drug Eluting

SummaryGiven conflicting data on temporal variability in pharmacodynamic platelet responses to clopidogrel, we investigated platelet reactivity on clopidogrel and aspirin for up to six months after elective percutaneous coronary intervention (PCI) with drug-eluting stents. Platelet reactivity was determined in 102 patients before loading with clopidogrel and aspirin, and on maintenance therapy after PCI on day 1, at one month and six months by VerifyNow™ P2Y12 and Aspirin assays and by residual platelet aggregation (RPA) on light transmission aggregometry using adenosine diphosphate and arachidonic acid. By VerifyNow testing, median (interquartile range) P2Y12 reaction units (PRU) on clopidogrel were 166 (90–234), 195 (124–257), and 198 (141–252) on day 1, one month and six months after PCI, respectively (p=0.005 day 1 to 1 month, and p=0.86 1 month to 6 months). Using a cut-off of > 208 PRU, 35% of patients had high platelet reactivity (HPR) to clopidogrel on day 1, 43% at one month, and 46% at six months after PCI. Between day 1 and six months after PCI, 38.2% of patients changed clopidogrel responder status at least once. Other cut-offs and RPA yielded similar results. Platelet inhibition by aspirin was consistent over time with only five patients being characterised as having HPR. Considerable variation in individual on-clopidogrel platelet reactivity was present during both the subacute and the late phases of maintenance therapy after elective PCI. Hence, the utility of contemporary platelet function testing to guide antiplatelet therapy may be limited.

Aspirin I.V. Loading during Elective Percutaneous Coronary Intervention

Pharmacology ◽  
2021 ◽  
pp. 1-5
Author(s):  
David Naguib ◽  
Carolin Helten ◽  
Saif Zako ◽  
Philipp Mourikis ◽  
René M’Pembele ◽  
...  
Keyword(s):  
Pilot Study ◽  
Light Transmission ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Bleeding Complications ◽  
Loading Dose ◽  
Bleeding Events ◽  
Elective Percutaneous Coronary Intervention ◽  
Percutaneous Coronary ◽  
The Impact

Additional loading dose of acetylsalicylic acid (ASA) during percutaneous coronary interventions (PCIs) despite permanent oral ASA medication is frequently applicated. The impact on platelet reactivity and clinical events is not known. In this pilot study, we aimed to analyze high on-treatment platelet reactivity (HTPR) to aspirin in patients undergoing elective PCI. Platelet reactivity was measured using light-transmission aggregometry in 100 patients on permanent low-dose ASA medication undergoing elective PCI. Platelet reactivity measured by arachidonic acid-induced maximum of aggregation (MoA) in patients with versus without additional peri-procedural ASA loading (500 mg i.v.) was compared. HTPR was defined as MoA &#x3e;20% for ASA. Major adverse cerebro- and cardiovascular events (MACCEs) and bleeding events were evaluated during hospital course. HTPR rate was similar in both groups (HTPR to ASA: loading vs. control 6% vs. 16%, odds ratio [OR] = 0.33, 95% confidence interval [CI] 0.08–1.35, <i>p</i> = 0.12). In-hospital MACCEs were not different between groups (MACCE: loading vs. control: 0 vs. 0 patient, OR = 1.32, 95% CI 0.03–67.95, <i>p</i> = 0.89). Thrombolysis in myocardial infarction minimal bleedings were numerically higher in patients without ASA loading dose. In this pharmacodynamic pilot study, additional ASA loading did not reduce HTPR to ASA. Furthermore, ASA loading did not increase in-hospital MACCE and bleeding complications.

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.

scholarly journals Stent Thrombosis: Incidence, Predictors and New Technologies

Thrombosis ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Gill Louise Buchanan ◽  
Sandeep Basavarajaiah ◽  
Alaide Chieffo
Keyword(s):  
Stent Thrombosis ◽  
New Technologies ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Drug Eluting Stent ◽  
Very Late Stent Thrombosis ◽  
Percutaneous Coronary ◽  
Drug Eluting ◽  
The Individual

Some concerns have been raised regarding the risk of late and very late stent thrombosis (ST) following drug-eluting stent implantation. Despite remaining an uncommon complication of percutaneous coronary intervention, when ST occurs, it can be catastrophic to the individual, commonly presenting as acute ST elevation myocardial infarction or sudden cardiac death. The incidence and predictors of ST have been reported in the literature and the role of dual antiplatelet therapies in the avoidance of such a complication remains vital. Ongoing studies are assessing the role of these therapies including platelet reactivity testing, genetic testing and optimum duration of therapy. In addition, newer polymer-free and bioabsorbable stents are under investigation in the quest to potentially minimise the risk of ST.

Diurnal Variability of On-Treatment Platelet Reactivity in Clopidogrel versus Prasugrel Treated Acute Coronary Syndrome Patients: A Pre-Specified TROPICAL-ACS Sub-Study

2019 ◽  
Vol 119 (04) ◽  
pp. 660-667 ◽  
Author(s):  
Matthias Freynhofer ◽  
Ralph Hein-Rothweiler ◽  
Paul Haller ◽  
Daniel Aradi ◽  
Döme Dézsi ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Early Morning ◽  
Platelet Inhibition ◽  
Control Group ◽  
Diurnal Variability ◽  
Coronary Syndrome ◽  
Adp Receptor

AbstractLong-term evidence supports a clustering of cardiovascular events in the early morning and smaller mechanistic studies in aspirin-treated patients have shown increased platelet reactivity at the end of the dosing interval. Comparative pharmacodynamic analyses for different adenosine diphosphate (ADP) receptor inhibitors in percutaneous coronary intervention-treated acute coronary syndrome (ACS) patients are lacking and this pre-specified analysis from the randomized Testing Responsiveness To Platelet Inhibition On Chronic Antiplatelet Treatment For Acute Coronary Syndromes (TROPICAL-ACS) trial aimed for the first time at investigating diurnal variability of on-treatment platelet reactivity in clopidogrel versus prasugrel treated patients. TROPICAL-ACS randomized 2,610 ACS patients to either treatment with prasugrel (control group) or to a platelet function testing-guided de-escalation of anti-platelet treatment with a switch to clopidogrel (guided de-escalation group). This study design enabled a diurnal comparison of on-prasugrel versus on-clopidogrel treatment platelet reactivity under steady-state conditions. For 2,526 patients (97%), both the exact time of blood sampling and the ADP-induced platelet aggregation value (in units, Multiplate analyser) were available. Platelet reactivity in patients on clopidogrel (n = 1,265) was higher and subject to significant diurnal variability (p = 0.019) with a peaking of platelet reactivity in the early morning (5–10 a.m.). In prasugrel-treated patients (n = 1,261), there was no sign for diurnal variability (p = 0.174) or a peaking of platelet reactivity in the morning. The potent ADP receptor inhibitor prasugrel is not subject to diurnal variability while we observed a significant diurnal variability of on-clopidogrel platelet reactivity. The clinical impact of this observation may differ for patients with and without an adequate response to clopidogrel treatment and the issue of diurnal variability of platelet reactivity in ACS patients warrants further investigation.

scholarly journals Validation of a New ELISA-Based Vasodilator-Associated Stimulated Phosphoprotein Phosphorylation Assay to Assess Platelet Reactivity Index in a Chinese Population

2017 ◽  
Vol 24 (3) ◽  
pp. 452-461 ◽  
Author(s):  
Peng Ding ◽  
Yujie Wei ◽  
Nana Chen ◽  
Huiliang Liu
Keyword(s):  
Acute Coronary Syndrome ◽  
Healthy Volunteers ◽  
Chinese Population ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
Reactivity Index ◽  
Enzyme Linked Immunosorbent Assay ◽  
Coronary Syndrome

The level of platelet reactivity during P2Y12-adenosine diphosphate receptor antagonist is associated with ischemic and bleeding risks following percutaneous coronary intervention in acute coronary syndrome. Determining platelet reactivity inhibition may be valuable for confirming effective platelet inhibition for individual patients and identifying patients at risk of bleeding. The enzyme-linked immunosorbent assay (ELISA)-based vasodilator-stimulated phosphoprotein (VASP) assay offers unique advantages over other methods and has not been used in the Chinese population. We enrolled 10 healthy volunteers and 54 patients with acute coronary syndrome. The volunteers received no treatment, and patients were administered a loading dose of clopidogrel or ticagrelor. The platelet reactivity index (PRI) was measured using flow cytometry (FC)-VASP and ELISA-VASP at baseline and 8-hour postloading dose. Blood samples of healthy volunteers and clopidogrel- or ticagrelor-treated patients were frozen and stored for 1, 2, and 4 weeks after initial activation. All frozen samples were tested using ELISA-VASP. The PRI assessed by FC-VASP and ELISA-VASP correlated well showing a high degree of consistency in identifying high or low on-treatment platelet reactivity. No significant time-dependent changes in PRI results were observed in frozen samples stored up to 4 weeks compared to nonfrozen samples. The PRI of ticagrelor-treated patients was lower than that of clopidogrel-treated patients. The ELISA-VASP effectively assesses the PRI, and results obtained from frozen specimens are unaffected by storage and shipment prior to assay. Ticagrelor was superior to clopidogrel in decreasing the PRI.

Impact of Reticulated Platelets on the Antiplatelet Effect of the Intravenous P2Y12-Receptor Inhibitor Cangrelor

2018 ◽  
Vol 118 (02) ◽  
pp. 362-368 ◽  
Author(s):  
Christian Stratz ◽  
Thomas Nührenberg ◽  
Christian Valina ◽  
Nikolaus Löffelhardt ◽  
Kambis Mashayekhi ◽  
...  
Keyword(s):  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
P2y12 Receptor ◽  
Elective Percutaneous Coronary Intervention ◽  
Reticulated Platelets ◽  
Impedance Aggregometry ◽  
Percutaneous Coronary ◽  
The Impact ◽  
Receptor Inhibitor

Background Reticulated platelets are associated with impaired antiplatelet response to irreversibly acting P2Y12-receptor inhibitors. However, the impact of reticluated platelets (RP) on the reversibly acting injectable P2Y12-receptor inhibitor cangrelor is unknown. Thus, this study sought to investigate the influence of RP on cangrelor and transitioning strategies to oral P2Y12-receptor inhibitors. Methods This study randomized 110 patients undergoing elective percutaneous coronary intervention with use of cangrelor to different oral transitioning strategies loading with prasugrel 60 mg or ticagrelor 180 mg at the start of cangrelor (n = 45 each) or loading with clopidogrel 600 mg after discontinuation of cangrelor (n = 20). ADP-induced platelet reactivity was assessed by impedance aggregometry. Reticulated platelets were analysed by an automated whole blood flow cytometry and described as immature platelet count. Results There was no correlation of reticulated platelets and ADP-induced platelet reactivity in patients under treatment with cangrelor (r = 0.06, p = 0.47). This finding was consistent in all three transitioning strategies. On day 1 following treatment with cangrelor, the correlation of reticulated platelets and platelet reactivity was detectable again in patients receiving thienopyridines but not ticagrelor (all patients r = 0.37, p < 0.001; clopidogrel: r = 0.59, p = 0.01; prasugrel: r = 0.47, p < 0.001; ticagrelor r = 0.22, p = 0.13). Conclusion Platelet inhibition is not influenced by levels of reticulated platelets during infusion of cangrelor independent of oral P2Y12-receptor inhibitor transitioning strategy. These findings underline the potency of cangrelor as immediate and reversibly acting P2Y12-receptor inhibitor.

Abstract 13003: Efficacy of Cilostazol on Platelet Reactivity and Cardiovascular Outcomes in Patients Undergoing Percutaneous Coronary Intervention: Insights From a Meta-Analysis of Randomized Trials

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Bora Toklu ◽  
Amita Singh ◽  
Frederick Feit ◽  
Sripal Bangalore
Keyword(s):  
Antiplatelet Therapy ◽  
Stent Thrombosis ◽  
Randomized Trials ◽  
Dual Antiplatelet Therapy ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
Percutaneous Coronary ◽  
Drug Eluting ◽  
Secondary Outcomes

Introduction: Cilostazol overcomes high on-treatment platelet reactivity (HTPR) and reduce adverse cardiovascular (CV) outcomes after percutaneous coronary intervention (PCI). However, the role for triple antiplatelet therapy (TAPT) with cilostazol in addition to aspirin and clopidogrel after PCI is not well defined. Methods: We conducted a MEDLINE/EMBASE/CENTRAL search for randomized trials, until May 2014, evaluating TAPT compared with dual antiplatelet therapy (DAPT) of aspirin and clopidogrel alone in patients undergoing PCI and reporting platelet reactivity and/or CV outcomes. The primary platelet reactivity outcome was differences in platelet reactivity unit (PRU) with secondary outcomes of %platelet inhibition and rate of HTPR. The primary CV outcome was major adverse cardiovascular events (MACE), with secondary outcomes of death, cardiovascular death, myocardial infarction (MI), stent thrombosis (ST), target lesion revascularization (TLR), and target vessel revascularization (TVR) as well as safety outcomes of bleeding and drug discontinuations. Results: In 17 trials that evaluated platelet reactivity outcomes, the mean PRU value was 47.73units lower with TAPT vs. DAPT (95% CI -61.41 to -34.04, P <0.0001; mean PRU 182.90 vs. 232.65). TAPT also reduced platelet inhibition by 12.71% (95% CI 10.76-14.67, P <0.0001), and led to a 60% reduction in the risk of HTPR (RR=0.40; 95% CI 0.30-0.53) compared with DAPT. Moreover, among the 34 trials that evaluated CV outcomes, TAPT reduced the risk of MACE (IRR=0.68; 95% CI 0.60-0.78), TLR (IRR=0.57; 95% CI 0.44-0.73), TVR (IRR=0.69; 95% CI 0.59-0.81) and stent thrombosis (IRR=0.63; 95% CI 0.40-0.98) with no difference for other outcomes including bleeding, even in trials using drug eluting stents. Drug discontinuation due to adverse effects was however higher with TAPT vs. DAPT (IRR=1.59; 95% CI 1.32-1.91). Conclusions: In patients undergoing PCI, addition of cilostazol to dual antiplatelet therapy results in decreased platelet reactivity and a significant reduction in CV outcomes including stent thrombosis, even in the drug eluting stent era.

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