Smoking promotes clopidogrel-mediated platelet inhibition in patients receiving dual antiplatelet therapy

2009 ◽  
Vol 124 (5) ◽  
pp. 588-591 ◽  
Author(s):  
Thomas Gremmel ◽  
Sabine Steiner ◽  
Daniela Seidinger ◽  
Renate Koppensteiner ◽  
Simon Panzer ◽  
...  
Keyword(s):  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Platelet Inhibition

scholarly journals Infections Deaths in the PLATO Trial

TH Open ◽  
2021 ◽  
Vol 05 (04) ◽  
pp. e503-e506
Author(s):  
Victor Serebruany ◽  
Jean-Francois Tanguay
Keyword(s):  
Antiplatelet Therapy ◽  
Drug Administration ◽  
Dual Antiplatelet Therapy ◽  
Food And Drug Administration ◽  
Platelet Inhibition ◽  
Public Domain ◽  
The Public ◽  
Local Evidence ◽  
Local Site ◽  
Therapeutic Outcomes

Abstract Background Cardiovascular benefits of aggressive dual antiplatelet therapy may be associated with extra risks including bleeding, cancer, and infections discovered first for prasugrel in the TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet InhibitioN with prasugrel (TRITON) trial. Ticagrelor in PLATO also caused slightly more infections but surprisingly less sepsis-related deaths (SRD) than clopidogrel. However, verified infection fatalities in PLATO were lacking from the public domain. We obtained the complete Food and Drug Administration (FDA)-issued primary causes death list, matched it with the few local site records dataset and analyzed the patterns of infections and deaths reported in PLATO. Methods Among infections, the FDA spreadsheet contains only two primary death codes for pneumonia (12–2) and SRD (12–8). We obtained local evidence for two pneumonia and two SRD and matched those with the FDA records. We assessed how SRD patterns were reported among nonvascular death's dataset. Results The FDA PLATO records indicate that clopidogrel caused numerically less (n = 8) primary pneumonia deaths than ticagrelor (n = 10) but over three times more SRD (n = 23/7). Among matched verifiable outcomes, both pneumonia deaths were correct, but two clopidogrel SRD were incorrect. Of the remaining 21 clopidogrel SRD, 6 were reported as two separate closed paired entries in Brazil (lines 76 and 78 and 86 and 88) and India (lines 436 and 440), suggesting last minute addition of potentially incorrect SRD reports. Four ticagrelor SRD (lines 24,193,467 and 650) were “compensated” with close or next in line clopidogrel SRD entries (lines 22,195,468 and 651). Conclusion The FDA-issued evidence suggests no benefit of ticagrelor in preventing deaths from infections with slightly more pneumonia deaths, with possible misreporting of SRD in PLATO. These findings require an in-depth precise review of sepsis deaths in this trial.

scholarly journals Thromboelastography for monitoring platelet function in unruptured intracranial aneurysm patients undergoing stent placement

2015 ◽  
Vol 21 (1) ◽  
pp. 61-68 ◽  
Author(s):  
Hongchao Yang ◽  
Youxiang Li ◽  
Yuhua Jiang ◽  
Xianli Lv
Keyword(s):  
Intracranial Aneurysm ◽  
Antiplatelet Therapy ◽  
Platelet Function ◽  
Dual Antiplatelet Therapy ◽  
Platelet Inhibition ◽  
Acute Ischemia ◽  
Unruptured Intracranial Aneurysm ◽  
Anterior Circulation ◽  
Permanent Disability ◽  
Significant Difference

This study evaluated patients’ preoperative platelet function and the relation between acute embolic or hemorrhagic complications in unruptured intracranial aneurysm patients undergoing stent treatment. From September 2013 to December 2013 we prospectively collected clinical data in all unruptured intracranial aneurysm patients undergoing stent-assisted coiling. All patients received a dual antiplatelet therapy (aspirin and clopidogrel) protocol. Diffusion-weighted 3-T MRI was performed for cerebral aneurysm patients within 24 hours after treatment. Platelet function was tested by thromboelastography. Forty-six patients with 50 intracranial aneurysms treated by stent-assisted coiling were included. Fifty-three stents were deployed in 46 procedures, including 39 Enterprise stents and 14 Solitaire stents. Acute ischemia was detected in the territory of the stented vessel in 25 of 46 patients (54.3%), but did not cause permanent disability. There was a significant difference between groups with and without thromboembolism in terms of percentage platelet inhibition and ADP-induced clot strength (MAADP) for clopidogrel, but no significant difference with aspirin. MAADP had a predictive value yielding an area under the ROC curve of 0.67 (95% CI: 0.57–0.81, P < 0.05). Anterior circulation aneurysms were also associated with ischemic events (P = 0.034). Silent acute embolism may be frequent in unruptured intracranial aneurysm treated with stent-assisted coiling even when dual antiplatelet therapy is given. The antiplatelet inhibition parameter (MAADP) was a predictor for acute thromboembolism in unruptured intracranial aneurysm patients treated by stent-assisted coiling.

Abstract 1032: High Clopidogrel Maintenance Dosing in Patients with Inadequate Platelet Inhibition: Functional Insights on Thienopyridine Usage According to Updated ACC/AHA/SCAI 2005 Guidelines for Percutaneous Coronary Interventions

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Dominick J Angiolillo ◽  
Marco A Costa ◽  
Steven B Shoemaker ◽  
Bhaloo Desai ◽  
Yuan Hang ◽  
...  
Keyword(s):  
Steady State ◽  
High Risk ◽  
Antiplatelet Therapy ◽  
Platelet Function ◽  
Maintenance Dose ◽  
Dual Antiplatelet Therapy ◽  
Platelet Inhibition ◽  
Percutaneous Coronary Interventions ◽  
Percutaneous Coronary ◽  
Risk Patients

Background: Clopidogrel under-dosing is a cause of inadequate platelet inhibition. Inadequate clopidogrel-induced antiplatelet effects have been associated with an increased risk of stent thrombosis. Updated guidelines for percutaneous coronary interventions (PCI) recommend to increase the dose of clopidogrel to 150mg in high risk patients if <50% platelet inhibition is demonstrated. However, to date there are no studies which have evaluated the functional impact of this recommendation. The aim of this study was determine the functional impact of a 150mg maintenance dose of clopidogrel in patients with 50% platelet inhibition while in their steady state phase of dual antiplatelet therapy. Methods: Platelet inhibition was screened by means of the VerifyNow P2Y 12 assay in patients in a steady state phase of dual antiplatelet therapy. Patients with <50% platelet inhibition were treated with 150mg of clopidogrel for one-month. Adenosine diphosphate-induced aggregation using light transmittance aggregometry and P2Y 12 reactivity ratio determined by vasodilator-stimulated phosphoprotein-phosphorylation analysis were also performed. Results: A total of 32 patients were screened to identify 20 with <50% platelet inhibition. Platelet inhibition increased from 28.3±12% to 43.2±18% in patients treated with 150mg of clopidogrel (p=0.004; primary endpoint). All other functional measures also showed that a high maintenance dose of clopidogrel reduces platelet function (Table ) . The degree of platelet inhibition achieved following one-month treatment with high dose clopidogrel broadly varied and only eight (40%) patients yielded a degree of platelet inhibition ≥50%. Conclusions: The use of a 150mg maintenance dose of clopidogrel in high risk patients with <50% platelet inhibition increases platelet inhibition. However, the antiplatelet effects achieved are non-uniform and a considerable number of patients persist with elevated platelet function. Platelet function analysis pre and post high clopidogrel maintenance dose therapy

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.

Separate dosing of clopidogrel and omeprazole may improve platelet inhibition on dual antiplatelet therapy

2011 ◽  
Vol 149 (1) ◽  
pp. 124-125 ◽  
Author(s):  
Bernadetta Chyrchel ◽  
Andrzej Surdacki ◽  
Michał Chyrchel ◽  
Dariusz Dudek ◽  
Jacek S. Dubiel
Keyword(s):  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Platelet Inhibition
Sign in / Sign up

Export Citation Format

Share Document