Title:Current Status of Antiplatelet Therapy in Acute Coronary Syndrome
VOLUME: 13 ISSUE: 1
Author(s):Debabrata Dash
Affiliation:S.L Raheja (A Fortis Associate) Hospital, Raheja rugnalaya Marg, Mahim (West), Mumbai 400016, India.
Keywords:Acute coronary syndrome, antiplatelet therapy, cardiovascular diseases, percutaneous coronary intervention,
pharmacokynetics, platelets.
Abstract:Antiplatelet therapy is a first-line medical treatment for patients with acute coronary
syndrome (ACS). As percutaneous coronary interventions (PCI) increase in number and complexity,
more patients must be treated with antiplatelet therapy for cardiovascular diseases in which arterial
thrombosis plays a major role. Current anti-platelet therapy is highly effective in preventing
atherothrombotic complications. Nevertheless, a significant number of patients continue to
experience recurrent complications despite being properly treated, due to pharmacokinetics and
interactions of drugs, genetic background and increased thrombus formation. This has lead to big
research efforts to provide new antiplatelet drugs with better preventive properties without increased bleeding risk. Up to
8% of patients receiving 81 mg-dose of aspirin have significantly less platelet inhibition than those receiving higher dose.
Patients with poor responsiveness to clopidogrel are at high risk of thromboembolic complications, especially in the
setting of ACS and stent implantation. Several options have been proposed. Firstly, to increase loading and maintenance
doses up to 600 mg and 75-mg twice daily associated with high-dose aspirin (300-325 mg). A second option would be to
change from clopidogrel to new antiplatelet agents like prasugrel and ticagrelor which were investigated in large clinical
trials in patients with different entities of ACS. Because of conflicting results & without large scale clinical studies,
routine platelet function measurement cannot be recommended at this point of time. Prasugrel is an ADP-P2Y12 receptor
inhibitor that has a faster and more consistent inhibitory effect of platelet aggregation and was shown to reduce
cardiovascular mortality in the setting of ACS undergoing PCI. Subgroups with increased risk of bleeding were patients
with prior stroke, age over 75 and body weight under 60 kg. In this population, prasugrel is discouraged despite its
increased in efficacy. Ticagrelor binds reversibly to P2Y12 receptor. The reversibility action makes it attractive for
situations when dual antiplatelet therapy needs to be interrupted. Both the drugs demonstrated superiority with respect to
the primary composite endpoint. As compared to clopidogrel, both prasugrel and ticagrelor do not depend on loss-offunction
genetic variants. The efficacy safety ratio of both compared to clopidogrel is better, even if both these
compounds increased the risk of spontaneous major bleedings significantly. Due to lack of head-to-head comparison,
potential differences between prasugrel and ticagrelor are hypothetical and both these drugs should be used according to
guidelines. The novel intravenous antiplatelet cangrelor cut thrombotic complications of PCI with some increase in
bleeding, a pooled analysis of the three CHAMPION(Cangrelor versus Standard Therapy to Achieve Optimal
management of Platelet Inhibition) trials showed. Protease-activated-receptor 1(PAR 1) antagonist vorapaxar did not
reduce the primary composite ischemic end point in TRACER (Thrombin Receptor Antagonist Clinical Event reduction
in acute coronary syndrome) trial, but major bleeding and intracranial hemorrhage rates were substantially increased.
Further large randomized trials would be required to decide the superiority of one agent over another and the duration of
the therapy.
