title: Clopidogrel withdrawal: is there a "rebound" phenomenon?
abstract: Dual antiplatelet therapy with aspirin and clopidogrel is routinely indicated in patients with acute coronary syndromes and following percutaneous coronary intervention to reduce the risk of cardiovascular mortality and ischaemic events. Although clinical guidelines recommend aspirin lifelong and clopidogrel for between one and 12 months, depending upon the indication, the optimal duration of clopidogrel therapy actually remains contentious. Premature cessation of clopidogrel in patients receiving drug-eluting stents is a clear risk factor for stent thrombosis, but recent clinical studies have also demonstrated a link between "appropriate" cessation of clopidogrel and clustering of adverse clinical events. It has been suggested that this may be due to a "rebound" prothrombotic and/ or proinflammatory response associated with clopidogrel withdrawal. This review will examine the definition and concept of a "rebound" phenomenon associated with clopidogrel cessation as well as the likely mechanisms behind this effect. Within the context of clinical event clustering after clopidogrel cessation, we will also discuss (i) the clinical importance of clopidogrel and the increasing uncertainty surrounding optimal duration of therapy, (ii) the antiplatelet and anti-inflammatory properties of clopidogrel and, in particular, its influence on arachidonic acid pathways traditionally thought to be mediated predominantly by aspirin and (iii) the role of newer, more potent antiplatelet agents and potential changes to antiplatelet therapy prescribing guidelines in the future.
authors.affiliation: Wessex Cardiothoracic Unit, Southampton University Hospital, UK.
authors.forename: Nalyaka
authors.initials: N
authors.lastname: Sambu
authors.forename: Timothy
authors.initials: T
authors.lastname: Warner
authors.forename: Nick
authors.initials: N
authors.lastname: Curzen
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy*; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D001241:Aspirin / Q000008:administration & dosage; D000077144:Clopidogrel; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006801:Humans; D018579:Patient Selection; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D017410:Practice Guidelines as Topic; D018570:Risk Assessment; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin