Optimizing P2Y12 Receptor Inhibition in Patients With Acute Coronary Syndrome on the Basis of Platelet Function Testing

Aradi, Dániel; Tornyos, Adrienn; Pintér, Tünde; Vorobcsuk, András; Kónyi, Attila; Faluközy, József; Veress, Gábor; Magyari, Balázs; Horváth, Iván; Komócsi, András

doi:10.1016/j.jacc.2013.12.023

Cited by 82 publications

(25 citation statements)

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“…In ACS patients exhibiting HPR on clopidogrel after PCI, both ticagrelor and prasugrel provide effective and sufficient platelet inhibition [40]. Studies have demonstrated that in patients with HPR, switching to prasugrel achieved adequate platelet inhibition and reduced thrombotic events [41, 42]. With increasing usage of newer P2Y 12 inhibitors for coronary intervention, it may seem less necessary to concern about platelet resistance.…”

Section: Discussionmentioning

confidence: 99%

Individualized dual antiplatelet therapy based on platelet function testing in patients undergoing percutaneous coronary intervention: a meta-analysis of randomized controlled trials

Zhou

Wang

et al. 2017

BMC Cardiovasc Disord

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Background: High on-treatment platelet reactivity (HPR) represents a strong risk factor for thrombotic events after PCI. We aim to evaluate the efficacy and safety of individualizing intensified dual antiplatelet therapy (DAPT) in PCI-treated patients with HPR based on platelet function testing (PFT). Methods: Electronic databases were searched for randomized control trials that reported the clinical outcomes of using an intensified antiplatelet protocol with P2Y 12 receptor inhibitor comparing with standard maintenance dose of clopidogrel on the basis of platelet function testing. Clinical endpoints were assessed. Results: From 2005 to 2016, thirteen clinical studies comprising 7290 patients were included for analysis. Compared with standard antiplatelet therapy with clopidogrel, the intensified protocol based on platelet function testing was associated with a significant reduction in major adverse cardiovascular events (RR:0.55, 95% CI: 0.36-0.84, p = 0.005), cardiovascular death (RR:0.60, 95% CI: 0.38-0.96, p = 0.03), stent thrombosis (RR:0.58, 95% CI: 0.36-0.93, p = 0.02) and target vessel revascularization (RR:0.33, 95% CI: 0.14-0.76, p = 0.009). No significant difference was found in the rate of bleeding events between intensified and standard protocol. Conclusions: Compared with standard clopidogrel therapy, individualized intensified antiplatelet therapy on the basis of platelet reactivity testing reduces the incidence of cardiovascular events in patient undergoing PCI, without increasing the risk of bleeding.

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Section: Discussionmentioning

confidence: 99%

Individualized dual antiplatelet therapy based on platelet function testing in patients undergoing percutaneous coronary intervention: a meta-analysis of randomized controlled trials

Zhou

Wang

et al. 2017

BMC Cardiovasc Disord

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“…49 Many other studies exploring the pharmacodynamic profiles of switching from clopidogrel to prasugrel or ticagrelor have been conducted (Tables II and III in the online-only Data Supplement). 18,[48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66] All studies have consistently shown enhanced platelet inhibition when escalating from clopidogrel to prasugrel or ticagrelor, regardless of clinical setting, as well as a reduction in rates of high on-treatment platelet reactivity (HPR), 18,48-70 a well-defined marker of risk of ischemic recurrences, including stent thrombosis. 10,11 These effects are achieved more promptly after administration of an LD compared with an MD regimen.…”

Section: Escalation (Switching From Clopidogrel To Prasugrel or Ticagmentioning

confidence: 99%

International Expert Consensus on Switching Platelet P2Y ₁₂ Receptor–Inhibiting Therapies

et al. 2017

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Dual antiplatelet therapy with aspirin and a P2Y 12 inhibitor is the treatment of choice for the prevention of atherothrombotic events in patients with acute coronary syndromes and for those undergoing percutaneous coronary interventions. The availability of different oral P2Y 12 inhibitors (clopidogrel, prasugrel, ticagrelor) has enabled physicians to contemplate switching among therapies because of specific clinical scenarios. The recent introduction of an intravenous P2Y 12 inhibitor (cangrelor) further adds to the multitude of modalities and settings in which switching therapies may occur. In clinical practice, it is not uncommon to switch P2Y 12 inhibitor, and switching may be attributed to a variety of factors. However, concerns about the safety of switching between these agents have emerged. Practice guidelines have not fully elaborated on how to switch therapies, leaving clinicians with limited guidance on when and how to switch therapies when needed. This prompted the development of this expert consensus document by key leaders from North America and Europe with expertise in basic, translational, and clinical sciences in the field of antiplatelet therapy. This expert consensus provides an overview of the pharmacology of P2Y 12 inhibitors, different modalities and definitions of switching, and available literature and recommendations for switching between P2Y 12 inhibitors. Dual antiplatelet therapy with aspirin and a platelet P2Y 12 receptor antagonist (P2Y 12 inhibitor) is the treatment of choice for the prevention of atherothrombotic events in patients with acute coronary syndromes (ACS) and for those undergoing percutaneous coronary intervention (PCI).1,2 Clopidogrel, prasugrel, and ticagrelor are the most commonly used oral platelet P2Y 12 inhibitors; the use of ticlopidine, the first available P2Y 12 inhibitor, has been largely abandoned. 3Clopidogrel is the only oral P2Y 12 inhibitor indicated for the treatment of patients with stable coronary artery disease.1,2 Although all 3 agents have an indication for use in ACS, current guidelines support the preferential use of prasugrel and ticagrelor over clopidogrel because of their superior net clinical benefits.1,2,4-6 Nevertheless, clopidogrel remains widely prescribed. 7,8 The availability of different oral P2Y 12 inhibitors has enabled physicians to contemplate switching among therapies because of specific clinical scenarios. 9 The recent introduction of an intravenous P2Y 12 inhibitor (ie, cangrelor) further adds to the multitude of modalities and settings in which switching therapies may occur. 6 A variety of factors may contribute to the decision to switch, including the clinical setting, patient characteristics, concomitant therapies, costs, social issues, development of side effects, medication adherence, and patient/physician preference. Therefore, it is not uncommon to change P2Y 12 inhibitor. However, concerns about the safety of switching between these agents have emerged. At present, data from large-scale clinical studie...

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“…Ticagrelor is an orally active drug not requiring biotransformation and binds rapidly and reversibly to the P2Y12 receptor, making it an attractive direct P2Y12 inhibitor. 46 Strategies for overcoming antiplatelet drug resistance include increasing initial loading doses (eg, aspirin: 100-300 mg; clopidogrel: 75-600 mg; prasugrel: 10-60 mg; ticagrelor: 90-180 mg) 43,45,47 and personalized dose adjustment (eg, increase the maintenance dose of clopidogrel to 150 mg daily 53,54 or drug switching from clopidogrel to prasugrel 53,55,56 or ticagrelor) that may include adjustment based on regular testing platelet function monitoring. 50 The lack of effect of individualized antiplatelet therapy by platelet function testing in recent large randomized studies in PCI and medically managed patients with coronary artery disease is disappointing.…”

Section: Aspirin and Clopidogrel Resistancementioning

confidence: 99%

Current State and Novel Approaches of Antiplatelet Therapy

Metharom

Berndt

Baker

et al. 2015

ATVB

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Abstract-An unresolved problem with clinical use of antiplatelet therapy is that a significant number of individuals either still get thrombosis or run the risk of life-threatening bleeding. Antiplatelet drugs are widely used clinically, either chronically for people at risk of athero/thrombotic disease or to prevent thrombus formation during surgery. However, a subpopulation may be resistant to standard doses, while the platelet targets of these drugs are also critical for the normal hemostatic function of platelets. In this review, we will briefly examine current antiplatelet therapy and existing targets while focusing on new potential approaches for antiplatelet therapy and improved monitoring of effects on platelet reactivity in individuals, ultimately to improve antithrombosis with minimal bleeding. Primary platelet adhesion-signaling receptors, glycoprotein (

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Optimizing P2Y12 Receptor Inhibition in Patients With Acute Coronary Syndrome on the Basis of Platelet Function Testing

Abstract: Switching patients with ACS who have HPR to treatment with prasugrel reduces thrombotic and bleeding events to a level similar to that of those without HPR; however, there is a higher risk of both thrombotic and bleeding complications with high-dose clopidogrel.

Cited by 82 publications

References 16 publications

Individualized dual antiplatelet therapy based on platelet function testing in patients undergoing percutaneous coronary intervention: a meta-analysis of randomized controlled trials

Individualized dual antiplatelet therapy based on platelet function testing in patients undergoing percutaneous coronary intervention: a meta-analysis of randomized controlled trials

International Expert Consensus on Switching Platelet P2Y ₁₂ Receptor–Inhibiting Therapies

Current State and Novel Approaches of Antiplatelet Therapy

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Optimizing P2Y12 Receptor Inhibition in Patients With Acute Coronary Syndrome on the Basis of Platelet Function Testing

Abstract: Switching patients with ACS who have HPR to treatment with prasugrel reduces thrombotic and bleeding events to a level similar to that of those without HPR; however, there is a higher risk of both thrombotic and bleeding complications with high-dose clopidogrel.

Cited by 82 publications

References 16 publications

Individualized dual antiplatelet therapy based on platelet function testing in patients undergoing percutaneous coronary intervention: a meta-analysis of randomized controlled trials

Individualized dual antiplatelet therapy based on platelet function testing in patients undergoing percutaneous coronary intervention: a meta-analysis of randomized controlled trials

International Expert Consensus on Switching Platelet P2Y 12 Receptor–Inhibiting Therapies

Current State and Novel Approaches of Antiplatelet Therapy

Contact Info

Product

Resources

About

International Expert Consensus on Switching Platelet P2Y ₁₂ Receptor–Inhibiting Therapies