Efficacy and safety of intensified antiplatelet therapy on the basis of platelet reactivity testing in patients after percutaneous coronary intervention: Systematic review and meta-analysis.

University of Pécs, Heart Institute, Pécs, Hungary.
International journal of cardiology (Impact Factor: 6.18). 06/2012; DOI: 10.1016/j.ijcard.2012.05.100
Source: PubMed

ABSTRACT BACKGROUND: ADP-specific platelet function assays were shown to predict thrombotic events, and might be helpful to select candidates for more potent antiplatelet therapy. We aimed to determine the efficacy and safety of giving intensified antiplatelet therapy on the basis of platelet reactivity testing for patients undergoing percutaneous coronary intervention (PCI). METHODS: Electronic databases were searched to find prospective, randomized trials that reported the clinical impact of using an intensified antiplatelet protocol (repeated loading or elevated maintenance doses of clopidogrel, prasugrel or glycoprotein IIb/IIIa inhibitor) on the basis of ADP-specific platelet reactivity testing (VerifyNow, Multiplate, VASP or light transmission aggregometry) compared to standard-dose clopidogrel. Evaluated efficacy measures included cardiovascular death, non-fatal myocardial infarction and definite/probable stent thrombosis (ST), while major bleeding events were recorded as safety endpoint. RESULTS: Between 2008 and 2011, 10 clinical trials comprising 4213 randomized patients were identified. Compared to standard antiplatelet therapy, the intensified protocol was associated with a significant reduction in cardiovascular mortality, ST and myocardial infarction (p<0.01 for all). There was no difference in the rate of major bleeding events between intensified and standard groups (p=0.44). Although the observed effects regarding mortality, ST and bleeding were not heterogeneous, meta-regression analysis revealed that the net clinical benefit of the intensified treatment significantly depended on the risk of ST with standard-dose clopidogrel (p=0.023). CONCLUSION: Intensifying antiplatelet therapy on the basis of platelet reactivity testing reduces cardiovascular mortality and ST after PCI; however, the net benefit of this approach depends on the risk of ST with standard-dose clopidogrel.

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    ABSTRACT: Dual antiplatelet therapy with a combination of aspirin and an inhibitor of the ADP P2Y12 receptor is the recommended treatment for patients with acute coronary syndrome or who are undergoing percutaneous coronary intervention (PCI). However, patients may continue to have ischemic recurrences, including stent thrombosis, which have been linked with the well-known variability in individual response to antiplatelet therapy, and clopidogrel in particular. There are currently several assays available to measure platelet reactivity, and platelet function testing has been shown to be a valuable tool to assess the pharmacodynamic efficacy of antiplatelet drugs. Moreover, platelet reactivity has important prognostic implications, as several studies have shown an association with thrombotic and bleeding events in patients with high and low platelet reactivity, respectively. Consequently, over the past years there has been a plethora of studies investigating the optimal range of platelet reactivity associated with the highest protection against ischemic complications and the lowest risk of bleeding. Given the correlation between on-treatment platelet reactivity and outcomes, the use of platelet function testing has also been advocated to create personalized antiplatelet therapy. Several studies have been conducted in this field, but major clinical trials have failed to demonstrate a benefit of such a strategy in improving clinical outcomes. Indeed, inherent limitations of these trials may have contributed to their failure. The present manuscript provides an overview on the role of platelet function testing in contemporary clinical and interventional practice.
    Current Treatment Options in Cardiovascular Medicine 05/2014; 16(5):300.
  • International journal of cardiology 01/2014; · 6.18 Impact Factor
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    ABSTRACT: In clopidogrel treated patients undergoing percutaneous coronary intervention (PCI), high platelet reactivity (HPR) is associated with a higher risk for thrombotic events including stent thrombosis (ST). A personalised therapy with selective intensification of treatment may improve HPR patients´ outcome in this setting although recent randomised trials are against this hypothesis. The aim of the ISAR-HPR registry was to assess whether clopidogrel-treated HPR patients benefit from selective intensification of P2Y12 receptor inhibition. For the registry, outcomes were compared between two cohorts. We identified 428 clopidogrel treated HPR patients (AU x min ≥468 on the Multiplate analyser) between 2007-2008 (historical control cohort) without a change of treatment based on platelet function (PF) testing results. Between 2009-2011, we identified 571 HPR patients (guided therapy cohort) and used this information for guidance and selective intensification of P2Y12 receptor directed treatment (reloading with clopidogrel, switch to prasugrel, re-testing) in a setting of routine PF testing. The primary outcome was the composite of death from any cause or ST after 30 days. Major bleeding according to TIMI criteria was also monitored. The incidence of the primary outcome was significantly lower in the guided vs the control cohort (7 [1.2%] vs 16 [3.7%] events; HR 0.32, 95% CI 0.13-0.79; p=0.009). The incidence of major bleeding was numerically but not statistically higher in the guided vs the control cohort (1.9 vs 0.7%; p=0.10). In conclusion, present findings are in support for a PF testing guided antiplatelet therapy with selective intensification of P2Y12 receptor inhibition. The issue of personalised antiplatelet treatment warrants further investigation in randomized and well-controlled clinical trials.
    Thrombosis and Haemostasis 04/2014; 112(2). · 5.76 Impact Factor


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