Clopidogrel in ACS

OBJECTIVES: Patients with chronic kidney disease (CKD) are at high risk of death or myocardial infarction (MI) after percutaneous coronary interventions (PCI). We assessed whether prolonged dual antiplatelet therapy beyond the recommended 12 months may prevent adverse outcomes in patients with CKD receiving drug-eluting stents (DES) or bare-metal stents (BMS). METHODS: We studied all Veterans receiving PCI with BMS or first-generation DES in the Veterans Affairs (VA) Healthcare System between 2002 and 2006, classified by CKD (estimated glomerular filtration rate <60 mL/min) or normal renal function...

OBJECTIVES: This study sought to examine the possible drug-drug interactions between clopidogrel and morphine. BACKGROUND: Because morphine-the recommended treatment for pain of myocardial infarction-is associated with poor clinical outcome, we hypothesized that morphine lowers the plasma levels of clopidogrel active metabolite as well as its effects on platelets. METHODS: Twenty-four healthy subjects received a loading dose of 600 mg clopidogrel together with placebo or 5 mg morphine intravenously in a randomized, double-blind, placebo-controlled, cross-over trial...

Recent advances in our understanding of the role of the platelet in the atherosclerotic process beyond the acute formation of arterial blood clots, such as inflammation, have highlighted the role of antiplatelet agents as being much more than just 'blood thinners.' Some of the most important cardiovascular trials performed in the last 20 years have studied antiplatelet therapies. However, despite their long history, current global health implications and proven benefit, there remain substantial gaps in our understanding as to how to best utilize the limited number of antiplatelet agents available...

High on-treatment platelet reactivity (HTPR) on clopidogrel correlates with adverse outcomes in patients treated with percutaneous coronary intervention (PCI). Whether HTPR is a modifiable risk factor for future events is not clear. We evaluated the effect of serial clopidogrel dose adjustment based on platelet function testing (PFT) during 12 months of dual antiplatelet therapy (DAPT) using Multiplate) analyzer in patients with HTPR after PCI in acute coronary syndrome on clinical outcome. Eighty-seven patients were randomized to interventional (n = 43) and control group (n = 44)...

BACKGROUND: Current ST-elevation myocardial infarction (STEMI) guidelines recommend initiation of clopidogrel treatment as early as possible before angiography, based on pharmacokinetic and positive registry data. However, the mechanisms of the beneficial effect of clopidogrel pretreatment are unclear. Aim of this study was to investigate the impact of upstream clopidogrel on infarct size and microvascular obstruction (MO) assessed by cardiac magnetic resonance imaging (CMR) in STEMI patients...

Dual antiplatelet therapy with aspirin and clopidogrel is used to lower the risk of arterial thrombosis. However, this strategy is not always successful owing to high interindividual variability in response to antiplatelet therapy. To evaluate an impact of CYP2C19 G681A and CYP4F2 G1347A polymorphisms and clinical factors on dual antiplatelet effect of clopidogrel and aspirin. Totally 89 patients who continued dual aspirin and clopidogrel antiplatelet therapy for at least of 14 days were included into the further study...

OBJECTIVE: The effect of proton pump inhibitors (PPIs) on the pharmacokinetics and pharmacodynamics of clopidogrel was assessed in two healthy volunteer crossover studies. SUBJECTS AND METHODS: Study 1: subjects received clopidogrel alone (300-mg loading dose, then 75 mg/day for 28 days) and two of three PPIs (omeprazole 80 mg, esomeprazole 40 mg or lansoprazole 60 mg) plus clopidogrel for 29 days in three treatment periods (randomized treatment sequence assignment)...

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Several prospective studies have shown that high on-clopidogrel platelet reactivity (HPR) in patients undergoing percutaneous coronary intervention (PCI) is a risk factor for ischemic events. All studies were insufficiently powered to detect differences in stroke between patients with HPR and those without. Therefore, we performed a systematic review and meta-analysis of available publications aimed at determining whether patients undergoing PCI with HPR are also at increased risk of stroke. We searched for prospective studies enrolling patients undergoing PCI and treated with aspirin and clopidogrel that reported on clinical relevance of HPR to adenosine diphosphate...

OBJECTIVE: To review potential drug interactions between antiretroviral (ARV) medications and antiplatelets or novel oral anticoagulants (NOACs). DATA SOURCES: A literature search of MEDLINE, PubMed, EMBASE, International Pharmaceutical Abstracts, and Google Scholar was performed using the search terms (1) clopidogrel or ticagrelor or prasugrel, (2) dabigatran or rivaroxaban or apixaban, and (3) antiretrovirals. STUDY SELECTION AND DATA EXTRACTION: Any English language study or case report describing a drug interaction between an ARV and an antiplatelet or NOAC was included...

Decreased oral clopidogrel absorption caused by induction of intestinal permeability glycoprotein (P-gp) expression after aspirin administration was observed in rats. This study evaluated the effect of aspirin coadministration on the pharmacokinetics/pharmacodynamics of clopidogrel in humans. A single 75-mg dose of clopidogrel was orally administered before and after 2 and 4 weeks of once-daily 100-mg aspirin administration in 18 healthy volunteers who were recruited based on CYP2C19 and PON1 genotypes. Plasma concentrations of clopidogrel and its active metabolite, H4, and relative platelet inhibition (RPI) were determined...

BACKGROUND: High residual platelet reactivity in patients receiving clopidogrel is associated with an increased risk of a cardiovascular event after coronary stenting. The aim of our study was to evaluate the impact of the cytochrome P450 (CYP) 3A5 and CYP2C19 polymorphisms on platelet reactivity during dual antiplatelet therapy. METHODS: We determined the CYP2C19 and CYP3A5 genotypes of 101 angina patients (65 male patients, mean age 64 years) receiving dual antiplatelet therapy with aspirin and clopidogrel and evaluated the effect of these polymorphism on platelet reactivity at the early and late phases of treatment using a conventional light transmission aggregometry...

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There is little evidence on the optimal mode of clopidogrel discontinuation. Epidemiological studies observed clustering of thrombotic events after cessation of chronic clopidogrel therapy. The underlying mechanism has been ascribed to transient platelet hyper-reactivity. Gradual tapering of clopidogrel may have the potential to attenuate this phenomenon. The objective of the present study was to assess whether in patients with drug-eluting stents (DES) gradual discontinuation of clopidogrel maintenance therapy is superior to conventional, abrupt discontinuation...

In contrast to short thrombelastography (s-TEG) which utilises adenosine diphosphate (ADP) alone, the VerifyNow P2Y12 assay (VN-P2Y12) additionally uses prostaglandin E1 (PGE1) as agonist to assess response to P2Y12 inhibitors. Based upon previous observations, we hypothesised that VN-P2Y12 overestimates the therapeutic effects of clopidogrel. Simultaneous assay with s-TEG and VN-P2Y12 was performed in 43 healthy volunteers and 170 patients either on or off clopidogrel. Furthermore, in 27 patients on clopidogrel 75 mg we compared the effects of adding 22 nM PGE1 to ADP on platelet aggregation in s-TEG to ADP alone...

OBJECTIVES: This study sought to examine the effectiveness of clopidogrel in real-world, medically managed patients with unstable angina (UA) or non-ST-segment elevation myocardial infarction (NSTEMI). BACKGROUND: Although clinical trials have demonstrated the efficacy of clopidogrel to reduce cardiovascular (CV) morbidity and mortality in medically managed patients with UA or NSTEMI, the effectiveness of clopidogrel in actual clinical practice is less certain. METHODS: A retrospective cohort study was conducted of Kaiser Permanente Northern California members without known coronary artery disease or prior clopidogrel use who presented with UA or NSTEMI between 2003 and 2008 and were medically managed (i...

BACKGROUND: Sex-specific response to antiplatelet medications have been reported in several previous studies. OBJECTIVE: We investigated a possible connection between gender differences in hemorheological parameters and in vitro platelet aggregation in vascular patients treated with widely used antiplatelet agents. METHODS: In vitro platelet aggregation was assessed in 2687 patients treated with 100 mg acetylsalicylic acid (ASA), 1047 patients treated with 75 mg clopidogrel and 311 patients on dual antiplatelet therapy (100 mg aspirin and 75 mg clopidogrel) according to the method of Born...

INTRODUCTION: Current guidelines recommend antithrombotic therapy with either aspirin or clopidogrel for all patients with peripheral arterial disease (PAD). Nevertheless, cardiovascular comorbidities and perceived bleeding risk complicate antithrombotic management of PAD patients. We studied the proportion of patients receiving optimal (guideline-recommended) antithrombotic therapy, and second, assessed the impact of suboptimal antithrombotic therapy use to long-term outcomes of PAD patients...

No published information exists to support the safe use of ticagrelor in patients with a clopidogrel allergy. This study involved an institutional review board-approved retrospective review of patients with a documented clopidogrel allergy who subsequently received ticagrelor between July 2011 and February 2014. We report the cases of two patients with a history of hypersensitivity to clopidogrel in whom ticagrelor was used successfully without documented incident. In addition, principles suggesting a lack of cross-sensitivity between ticagrelor and clopidogrel are reviewed...

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