A Randomized Comparison of High Clopidogrel Loading Doses in Patients With Non–ST-Segment Elevation Acute Coronary Syndromes

Montalescot, Gilles; Sideris, Georges; Meuleman, Catherine; Bal-dit-Sollier, Claire; Lellouche, Nicolas; Steg, Philippe Gabriel; Slama, Michel; Milleron, Olivier; Collet, Jean‐Philippe; Henry, Patrick; Beygui, Farzin; Drouet, Ludovic

doi:10.1016/j.jacc.2006.04.090

Cited by 478 publications

(57 citation statements)

References 34 publications

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“…30 In addition, increasing LDs of clopidogrel does not confer more clinical benefit. 19,20 In recent years, several studies have been launched focusing on VASP-guided clopidogrel modification in patients on clopidogrel. Vasodilator-stimulated phosphoprotein is an intracellular actin-regulatory protein that is a substrate of both cAMP-dependent and cGMP-dependent protein kinases.…”

Section: Discussionmentioning

confidence: 99%

“…11 -13 Several methods have been developed to deal with clopidogrel resistance, 14 of which the most popular strategy is increasing the loading dose (LD) utilized in patients undergoing PCI to 600 mg 15 -18 and 900 mg. 19,20 Although clopidogrel response is dose-dependent, there is a threshold to its platelet-inhibitory effect when certain doses are administrated. 19,20 In order to find a better method to tackle clopidogrel resistance, Bonello et al 21 adjusted the clopidogrel LD according to platelet monitoring using the vasodilator-stimulated phosphoprotein (VASP) index in a multicenter randomized prospective study, and observed that it was safe and significantly improved the clinical outcomes after PCI in patients with clopidogrel resistance. In another study, Bonello et al 22 also demonstrated that tailoring the clopidogrel LD according to platelet reactivity monitoring decreased the rate of early stent thrombosis (ST) after PCI without increasing bleeding.…”

Section: Introductionmentioning

confidence: 99%

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Modifying Clopidogrel Maintenance Doses According to Vasodilator‐Stimulated Phosphoprotein Phosphorylation Index Improves Clinical Outcome in Patients With Clopidogrel Resistance

Wang

Dai-fu

Zhuang

et al. 2011

Clinical Cardiology

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Background: Despite dual antiplatelet therapy, the rate of major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) remains high. Ex vivo tests of clopidogrel resistance can predict MACE after PCI. The purpose of this study is to evaluate the clinical impact of adjusting phosphorylation analysis in patients with clopidogrel resistance undergoing PCI. Hypothesis: We hypothesized that VASP-guided clopidogrel maintenance doses, compared to fixed doses, improved clinical outcome. Methods: This monocentric, prospective, randomized study was performed on 306 patients undergoing PCI. Patients were randomized to a control group (n = 156) and to a vasodilator-stimulated phosphoprotein (VASP)-guided group (n = 150). In the VASP-guided group, patients received adjusted maintenance doses of clopidogrel to obtain platelet reactivity index (PRI) of <50% during 1 year after PCI. The primary endpoint was the rate of MACE. The secondary endpoints were major and minor bleeding. Results: All patients completed the PCI procedure and 298 patients completed follow-up. The control and VASP-guided groups had similar demographic, clinical, and angiographic characteristics. In the VASP-guided group, PRI was significantly decreased (from 72.1% ± 11.4% to 27.7% ± 8.4%; P = 0.001) in 128 patients (87.1% of all participants). During the 1-year follow-up, 14 MACEs were recorded in the VASP-guided group and 30 MACEs were recorded in the control group (9.3% vs 20.4%, respectively; P = 0.008). There was no difference in the rate of major and minor bleeding in the VASP-guided group compared with the control group (12.9% vs 16.6%; P = 0.06). Conclusions: Modifying clopidogrel maintenance doses according to platelet reactivity monitoring decreases the rate of MACE after PCI without increasing bleeding in patients with clopidogrel resistance during 1-year follow-up.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Modifying Clopidogrel Maintenance Doses According to Vasodilator‐Stimulated Phosphoprotein Phosphorylation Index Improves Clinical Outcome in Patients With Clopidogrel Resistance

Wang

Dai-fu

Zhuang

et al. 2011

Clinical Cardiology

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“…32 This finding was consistent with other previous studies. 33,34 Therefore, we suppose that the administration of first dosage of antiplatelet drug might rarely affect the predictive role of hsCRP in our study, given all patients received antiplatelet therapy. This speculation was affirmed by the similar distribution of hsCRP levels between our and other stroke studies.…”

Section: Strokementioning

confidence: 91%

High-Sensitive C-Reactive Protein Predicts Recurrent Stroke and Poor Functional Outcome

Li¹,

Wang²,

Meng³

et al. 2016

Stroke

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A cute minor ischemic stroke and transient ischemic attack (TIA) are common, and patients with recent stroke or TIA are at high risk for subsequent stroke. It is estimated that 10% to 20% of these patients have a stroke within 3 months after the index event, most of which even occur within the first 2 days. [1][2][3][4] Though several clinical risk factors have been reported to be associated with recurrent stroke, these characteristics do not fully explain the risk of recurrence of stroke. 5 Inflammation is increasingly recognized as playing a central role in atherosclerosis and cardiovascular disease. 6 High-sensitive C-reactive protein (hsCRP), one of the most investigated inflammatory makers in cardiovascular research, has been independently associated with increased risk of recurrent cardiovascular events. 7 However, the association between hsCRP and recurrent stroke is less established. [8][9][10] On the contrary, disability from stroke has brought huge personal and societal burden. Though the predictive value of hsCRP in mortality has been proved, 11,12 its association with functional disability in the patients with stroke is still undefined. 13,14 The CHANCE (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) trial showed that the combination of clopidogrel and aspirin was superior to aspirin alone in reducing recurrent stroke in patients with acute minor stroke or high-risk TIA during 90-day and 1-year Background and Purpose-Minor stroke and transient ischemic attack are common disorders with high rate of subsequent disabling stroke. We aim to investigate the role of high-sensitive C-reactive protein (hsCRP) in predicting recurrent stroke and poor functional outcome. Methods-In the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) trial, 3044 (59%) consecutive patients from 73 (64%) prespecified centers had hsCRP levels measured. The primary outcome was any stroke within 90 days. The secondary outcome included combined vascular events and dependence or death defined as modified Rankin Scale score of 2 to 6 at 90 days and a new vascular event during 1-year follow-up. The associations of hsCRP with recurrent stroke and functional outcome were analyzed by using Cox proportional hazards and logistic regression models. Results-Elevated hsCRP (>3.0 mg/L) was observed in 32% of the study population. Patients with hsCRP >3 mg/L had an increased risk of recurrent stroke (adjusted hazard ratio, 1.46; 95% confidence interval, 1.08-1.98; P=0.039), ischemic stroke and combined vascular events, and poor functional outcome (adjusted odds ratio, 1.68; 95% confidence interval, 1.22-2.32; P=0.002) compared with those with hsCRP <1 mg/L within 90-day follow-up period. High hsCRP levels also independently predicted recurrent stroke during 1-year follow-up. There was no interaction of hsCRP levels with randomized antiplatelet therapy. Conclusions-High

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“…It may also be related to the fact that a substantial fraction of the patients in the clopidogrel arm from the PLATO trial had received clopidogrel pretreatment and a large fraction also received a high clopidogrel loading dose. Given the need for clopidogrel to be transformed into its active metabolite to affect platelet function and given the improved metabolism and improved, more consistent, and faster inhibition of platelet function with increased loading doses, [21][22][23] both starting clopidogrel treatment early before PCI (rather than at the time of or after PCI) and using a 600-mg loading dose are associated with superior platelet inhibition and therefore will minimize the early contrast between randomized treatment arms. In addition, the use of intravenous glycoprotein IIb/IIIa blockers in both treatment arms is expected to minimize contrast in platelet inhibition between treatment arms during the acute phase.…”

Section: Downloaded Frommentioning

confidence: 99%

Stent Thrombosis With Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes

et al. 2013

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A Randomized Comparison of High Clopidogrel Loading Doses in Patients With Non–ST-Segment Elevation Acute Coronary Syndromes

Cited by 478 publications

References 34 publications

Modifying Clopidogrel Maintenance Doses According to Vasodilator‐Stimulated Phosphoprotein Phosphorylation Index Improves Clinical Outcome in Patients With Clopidogrel Resistance

Modifying Clopidogrel Maintenance Doses According to Vasodilator‐Stimulated Phosphoprotein Phosphorylation Index Improves Clinical Outcome in Patients With Clopidogrel Resistance

High-Sensitive C-Reactive Protein Predicts Recurrent Stroke and Poor Functional Outcome

Stent Thrombosis With Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes

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