Possibility of a rebound phenomenon following antiplatelet therapy withdrawal: a look at the clinical and pharmacological evidence.
The importance of regular administration of antiplatelet drugs in patients suffering from coronary artery disease stands on firm grounds, as large meta-analyses have shown these therapies to drastically reduce the risk of death. Although the current guidelines published jointly by the American Heart Association, the American College of Cardiology, the Society for Cardiovascular Angiography and Interventions, the American College of Surgeons and the American Dental Association stress the hazards of premature discontinuation of antiplatelet drugs, abrupt withdrawal remains widespread, with potentially catastrophic consequences. In the limited state of knowledge on antiplatelet drug withdrawal, an early sound of alarm has risen from early thromboembolic complications reported after the interruption of treatment in patients who require antiplatelet therapy for prevention of ischemic vascular disease. Acute thrombotic complications are not immediate and usually follow interruption of aspirin or clopidogrel therapy after a mean delay of 8-25 days, a time lapse consistent with normal platelet turnover required to replace the platelet pool in circulation and suggestive of a rebound phenomenon. This review article describes the thrombotic risks associated with discontinuing antiplatelet therapy and the bleeding risks associated with continuing these drugs. By integrating the current understanding of the pharmacology of antiplatelet agents and the kinetics of platelet function recovery, this article unveils the possibility of a pharmacological rebound phenomenon which could lead to adverse ischemic events, and supports the warning against premature discontinuation of antiplatelet drugs issued in current guidelines.
Faculty of Pharmacy, Université de Montréal, C.P. 6128, Succursale Centre Ville, Montréal, Québec H3C3J7, Canada.
Marie
M
Lordkipanidzé
Jean G
JG
Diodati
Chantal
C
Pharand
D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy; D004359:Drug Therapy, Combination; D006470:Hemorrhage / Q000209:etiology*; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D017410:Practice Guidelines as Topic; D012307:Risk Factors; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D028761:Withholding Treatment
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin