Platelet Inhibition in Acute Coronary Syndrome and Percutaneous Coronary Intervention: Insights from the Past and Present

Abstract

Platelet activation and aggregation have a pivotal role in arterial thrombosis and in the pathogenesis of both acute coronary syndromes (ACS) and in the thrombotic complications that occur in patients undergoing percutaneous coronary intervention (PCI). The past 30 years has seen the progress from early trials of clopidogrel and glycoprotein IIb/IIIa inhibitors to the application of more potent P2Y12 inhibitors prasugrel and ticagrelor. Early enthusiasm for newer and more potent antiplatelet agents, which could reduce ischemic events, has led to the understanding of the importance of bleeding and a desire to individualize and optimize treatment. It has increasingly become apparent that the potency and duration of dual antiplatelet therapy (DAPT) has to reflect the balance between ischemic and bleeding risk. Recently, multiple strategies have been proposed to individualize DAPT intensity and duration to reduce the bleeding and ischemic risks. Strategies of de-escalation of DAPT intensity, as well as shorter (less than a year) or more prolonged (beyond a year) treatment have been proposed, as well as platelet function test and genotype guidance of P2Y12 inhibitor therapy. Herein, we provide an overview of the progress in the field of antiplatelet therapy for ACS and PCI over the years, showing the current directions of travel. Ongoing studies focusing on personalized antiplatelet treatment will hopefully yield further insight into ways of optimizing outcomes for the individual.

Effect of remote ischaemic conditioning on platelet reactivity and endogenous fibrinolysis in ST-elevation myocardial infarction: a substudy of the CONDI-2/ERIC-PPCI randomized controlled trial

“…32 Up to a third of ACS patients demonstrate inadequate platelet inhibition in response to clopidogrel. 33 This is explained in part by polymorphisms in the gene encoding the hepatic enzyme CYP2C19, which transforms clopidogrel to its active metabolite, that can result in 5-12% variation in platelet inhibition. 34 There is ethnic variation in the prevalence of the loss-of-function CYP2C19 618G>A*2 allele, affecting some 30% of Caucasians and 50% of East Asians.…”

“…34 There is ethnic variation in the prevalence of the loss-of-function CYP2C19 618G>A*2 allele, affecting some 30% of Caucasians and 50% of East Asians. 33 Homozygotes for the CYP2C19*2 and less common CYP2C19*3 LoF alleles are poor metabolizers, and heterozygotes are intermediate metabolizers of clopidogrel, with high-on clopidogrel platelet reactivity and increased risk of adverse cardiovascular events, including AMI and stent thrombosis. [35][36][37] The association of CYP2C19 genotype with increased cardiovascular risk appears greatest in those undergoing PCI, and the risk is greater in Asians than in whites.…”

“…(Elecsys high-sensitivity assay, Roche Diagnostics); fibrinogen 2-4 g/L; PT 11-13.5 seconds; aPTT[25][26][27][28][29][30][31][32][33][34][35] …”

Use of Clopidogrel, Prasugrel, or Ticagrelor and Patient Outcome after Acute Coronary Syndrome in Austria from 2015 to 2017

“…Acute coronary syndrome (ACS) is the leading cause of morbidity and mortality in developed countries [ 1 ]. The combination of treatment with a platelet P2Y12 receptor inhibitor, such as clopidogrel, prasugrel, or ticagrelor with acetylsalicylic acid (dual antiplatelet therapy, DAPT), has been shown to prevent coronary peri-procedural thrombotic complications and recurrent ischemic events [ 2 , 3 ]. Randomized controlled trials have shown a reduced reoccurrence of ACS in patients treated with a DAPT comprising prasugrel or ticagrelor compared to clopidogrel [ 4 , 5 ].…”

Antithrombotic Therapy in Patients with Atrial Fibrillation and Acute Coronary Syndrome

“…From the other perspective, up to 36% of patients with AF have concomitant coronary artery disease (CAD) amongst whom 45% have prior MI [ 3 , 4 ]. Treatment of ACS, with or without percutaneous coronary intervention (PCI), requires the administration of dual antiplatelet therapy (DAPT) to prevent recurrent MI and stent thrombosis (ST) [ 5 , 6 ]. In most patients with AF, oral anticoagulation (OAC) is indicated for the prevention of stroke and systemic embolism [ 7 ].…”