Clopidogrel nonresponsiveness in patients undergoing percutaneous coronary intervention with stenting: A systematic review and meta-analysis

Snoep, Jaapjan D.; Hovens, Marcel M.C.; Eikenboom, Jeroen; Bom, Johanna G. van der; Jukema, J. Wouter; Huisman, Menno V.

doi:10.1016/j.ahj.2007.04.014

Cited by 392 publications

(254 citation statements)

References 49 publications

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“…Nevertheless the terms "clopidogrel resistance" and "clopidogrel non-responsiveness" continue to be widely used (1,(15)(16)(17)(18)(19)(20). These terms implicitly assume that all on-treatment platelet reactivity is dependent on the effects of clopidogrel.…”

Section: Discussionmentioning

confidence: 99%

“…Patient-to-patient variability in residual platelet function during clopidogrel therapy has been well described (1). Multiple studies indicate high residual platelet reactivity, also referred to as clopidogrel "resistance" or "non-responsiveness", is associated with poor clinical outcomes (1)(2)(3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

“…Multiple studies indicate high residual platelet reactivity, also referred to as clopidogrel "resistance" or "non-responsiveness", is associated with poor clinical outcomes (1)(2)(3)(4)(5). However, we (6) and others (2) have suggested that a portion of platelet function following treatment with standard dose clopidogrel (300 mg loading dose [LD], 75 mg daily maintenance dose [MD]) is accounted for by pretreatment platelet reactivity -and that clopidogrel "resistance" or "non-responsiveness" may therefore not be appropriate terms.…”

Section: Introductionmentioning

confidence: 99%

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Intrinsic platelet reactivity before P2Y12 blockade contributes to residual platelet reactivity despite high-level P2Y12 blockade by prasugrel or high-dose clopidogrel

Frelinger¹,

Michelson²,

Wiviott³

et al. 2011

Thromb Haemost

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SummaryIt was the objective of this study to determine whether the intrinsic platelet response to adenosine diphosphate (ADP) before thienopyridine exposure contributes to residual platelet reactivity to ADP despite high level P2Y 12 blockade by prasugrel (60 mg loading dose [LD]), 10 mg daily maintenance dose [MD]) or high-dose clopidogrel (600 mg LD, 150 mg daily MD). High residual platelet function during clopidogrel therapy is associated with poor clinical outcomes. It remains unknown whether the relationship between platelet reactivity prior to treatment with clopidogrel (300 mg LD, 75 mg daily MD) and residual on-treatment platelet reactivity is maintained after more potent P2Y 12 inhibition. PRINCIPLE-TIMI 44 was a randomised, double-blind, twophase crossover study of prasugrel compared with high-dose clopidogrel in 201 patients undergoing cardiac catheterisation for planned percutaneous coronary intervention. ADP-stimulated platelet-monocyte aggregates, platelet surface P-selectin and platelet aggregation were measured pre-treatment, during LD (6 h and 18-24 h) and MD (15 d). Correlations of pre-treatment to on-treatment values were determined by Spearman rank order. Prasugrel resulted in greater platelet inhibition than high-dose clopidogrel for each measure. However, for both drugs, pre-treatment reactivity to ADP predicted 6 h, 18-24 h and 15 day reactivity to ADP (correlations 0.24-0.62 for platelet-monocyte aggregates and P-selectin). In conclusion, a patient's intrinsic platelet response to ADP before exposure to thienopyridines contributes to residual platelet reactivity to ADP despite high level P2Y 12 blockade with high-dose clopidogrel or even higher level P2Y 12 blockade with prasugrel. Patients who are hyper-responsive to ADP pre-treatment are more likely to be hyper-responsive to ADP on-treatment, which may be relevant to therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Intrinsic platelet reactivity before P2Y12 blockade contributes to residual platelet reactivity despite high-level P2Y12 blockade by prasugrel or high-dose clopidogrel

Frelinger¹,

Michelson²,

Wiviott³

et al. 2011

Thromb Haemost

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“…high ontreatment platelet reactivity (HTPR), has been called to account repeatedly (5,6). HTPR after short-term therapy apparently is associated with an increased cardiovascular risk ranging from a modest increase up to odds ratios (OR) of 8, depending on the patient population and test systems studied (7)(8)(9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Multiple electrode aggregometry and vasodilator stimulated phosphoprotein-phosphorylation assay in clinical routine for prediction of postprocedural major adverse cardiovascular events

Freynhofer¹,

Brozovic²,

Bruno³

et al. 2011

Thromb Haemost

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SummaryReduced antiplatelet effect of clopidogrel assessed with multiple electrode aggregometry (MEA) and vasodilator stimulated phosphoprotein-phosphorylation (VASP-P) assay has been proven to predict major adverse cardiovascular events (MACE) after coronary stenting. So far no consecutive registry has evaluated the usefulness of different adenosine diphosphate-based platelet function tests to predict outcome in unselected patients. Hence, our objective was to determine the feasibility of MEA and VASP-P for clinical routine and whether low-response to clopidogrel as determined by MEA and/or the VASP-P assays predicts MACE in a "real-life" population undergoing coronary stenting. Threehundred consecutive patients were included in this prospective registry. Blood was sampled 6-24 hours after stenting to measure MEA and VASP-P. The use of glycoprotein-IIb/IIIa-blockers limited MEA to 196 measurements. Concerning the VASP-P assay, 300 measurements were achieved. Receiver Operating Characteristics (ROC)-curves of sensitiv- ity and specificity estimates for MACE were plotted for VASP-P assay. The area under the ROC-curve was 0.683 (p=0.014) for the platelet reactivity index (PRI) calculated from median fluorescence intensities (FI) with an optimal cut-off at 60.2% PRI. Patients above 60.2% had a significantly increased risk for MACE at six months follow-up (p=0.007). Estimating the cut-offs for the PRI from mean FI (52%) or from geometric mean FI (56.6%) led to clinically relevant differences. VASP-P assay is feasible for clinical routine to measure clopidogrel effects and to predict post-procedural MACE in unselected patients. With regard to differing cut-offs, exact standardisation of the VASP-P assay is mandatory. The use of GP-IIb/IIIa-blockers prevents MEA testing and limits its usability in unselected patients.

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“…This dose-independent resistance, which is seen in approximately one-fifth of all patients [63], eventually may lead to worse clinical outcomes including stent thrombosis and recurrent myocardial infarction [64][65][66]. To overcome these problems, other potential adenosine diphosphate P2Y 12 receptor antagonists (e.g.…”

Section: Antiplatelet Therapymentioning

confidence: 99%

Management of acute coronary syndrome: achievements and goals still to pursue. Novel developments in diagnosis and treatment

Boden

Hoeven

Karalis

et al. 2012

Journal of Internal Medicine

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. Boden H, van der Hoeven BL, Karalis I, Schalij MJ, Jukema JW (Leiden University Medical Center, Leiden, The Netherlands). Management of acute coronary syndrome: achievements and goals still to pursue. Novel developments in diagnosis and treatment (Review). J Intern Med 2012; 271: 521–536. Acute coronary syndromes contribute a substantial part of the global disease burden. To realize a reduction in mortality and morbidity, the management of patients with these conditions involves the integration of several different approaches. Timely delivery of appropriate care is a key factor, as the beneficial effect of reperfusion is greatest when performed as soon as possible. Innovations in antithrombotic therapy have also contributed significantly to improvements in the prevention of ischaemic complications. However, with the use of such treatment, an increase in the risk of bleeding is inevitable. Therefore, the greatest challenge is now to obtain an optimal balance between the prevention of ischaemic complications and the risk of bleeding. In this regard, identification of patients at highest risk of either one is essential.

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Clopidogrel nonresponsiveness in patients undergoing percutaneous coronary intervention with stenting: A systematic review and meta-analysis

Cited by 392 publications

References 49 publications

Intrinsic platelet reactivity before P2Y12 blockade contributes to residual platelet reactivity despite high-level P2Y12 blockade by prasugrel or high-dose clopidogrel

Intrinsic platelet reactivity before P2Y12 blockade contributes to residual platelet reactivity despite high-level P2Y12 blockade by prasugrel or high-dose clopidogrel

Multiple electrode aggregometry and vasodilator stimulated phosphoprotein-phosphorylation assay in clinical routine for prediction of postprocedural major adverse cardiovascular events

Management of acute coronary syndrome: achievements and goals still to pursue. Novel developments in diagnosis and treatment

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