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-of-function 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.