title: New anti-platelet agents: the end of resistance?
abstract: Despite improved clinical outcomes from dual anti-platelet therapy with aspirin plus the CYP12 ADP receptor antagonist clopidogrel in patients undergoing coronary revascularisation, ex-vivo platelet function testing consistently reveals a proportion of patients with apparent resistance or non-response to clopidogrel loading and maintenance therapy who are at increased risk of coronary thrombosis. Treatment regimens using the newer CYP12 antagonists prasugrel and ticagrelor demonstrate improved ex-vivo platelet inhibition and superior clinical efficacy in large-scale clinical trials-even in patients demonstrating clopidogrel resistance. However, improved efficacy comes at the cost of an increased overall risk of bleeding for both drugs. Further analysis of the outcomes from large scale clinical studies suggests that individual patient sub-groups differ both in their liklehood of bleeding with newer anti-platelet agents and with regard to efficacy outcomes. Therefore when deciding anti-platelet regimens in suspected acute coronary syndrome, particular consideration must be given to patient's risk of thrombosis (STEMI, previous stent thrombosis), the procedure (complex PCI, thrombus in-situ, strategy of pre-treatment), and factors affecting safety (patient age, patient weight, previous stroke, liklehood of surgical revascularisation). Placing the focus on individualised patient risk-benefit assessment with appropriate use of platelet function testing when indicated, in combination with the ongoing assessment of prasugrel and ticagrelor in larger numbers of patients should be the key strategies governing use of dual anti-platelet therapy.
authors.affiliation: German Heart Center Munich, Cardiology Department, Munich, Germany. kastrati@dhm.mhn.de
authors.forename: Adnan
authors.initials: A
authors.lastname: Kastrati
mesh_terms: D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000188:drug therapy*; D000077144:Clopidogrel; D015195:Drug Design; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D019317:Evidence-Based Medicine; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010979:Platelet Function Tests; D000068799:Prasugrel Hydrochloride; D011237:Predictive Value of Tests; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D058925:Receptors, Purinergic P2Y12 / Q000097:blood / Q000187:drug effects; D018570:Risk Assessment; D012307:Risk Factors; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: C548576:P2RY12 protein, human; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine