This article reviews the mechanisms and incidence of bleeding in patients treated with clopidogrel, the emerging evidence of a relation between bleeding and recurrent ischaemic events and death, and implications of bleeding for clinical practice and future research. 10– 12 These two observations highlight the need to re-examine the importance of bleeding in cardiovascular patients treated with antithrombotic drugs. 9 Further, with the increasing use of aggressive antithrombotic therapies and invasive revascularization procedures, the incidence of bleeding is increasing. The notion that haemorrhagic complications do not result in irreversible damage is now being challenged by emerging evidence that bleeding is associated with an increased risk of recurrent ischaemic events and death, even when the bleeding is not severe enough to be considered life-threatening. The reason being that ischaemic events cause irreversible complication, whereas even severe bleeding is rarely associated with permanent morbidity. In the past, clinicians have discounted bleeding complications in patients with acute coronary syndromes, provided that the antithrombotic regimens are effective in preventing irreversible ischaemia. 1– 8 Like all effective antithrombotic agents, clopidogrel use increases the risk of bleeding, which can be spontaneous or occur at sites of compromised vascular integrity. Future research efforts should be directed towards establishing whether or not the association between bleeding and recurrent ischaemic events and death is causal and to determine the mechanism(s) responsible for the association.Ĭlopidogrel, Bleeding, Myocardial infarction, Stroke, Death IntroductionĬlopidogrel is an effective antiplatelet drug for preventing myocardial infarction, stroke, and death in high-risk patients with symptomatic cardiovascular disease. The only way to overcome the antiplatelet effect of clopidogrel is with platelet transfusions because clopidogrel irreversibly inhibits platelet function for the life of the platelet, and there is no known antidote. Management of bleeding in patients treated with clopidogrel may include temporary discontinuation of antithrombotic drugs, resuscitation with intravenous fluid, packed red cell transfusion, and surgical or other procedures to control the bleeding. Possible strategies to reduce the risk of bleeding during clopidogrel treatment include appropriate dosing of concomitant antithrombotic drugs and their avoidance unless they are of proven benefit, careful selection of patient for invasive procedures, and discontinuation of clopidogrel at least 5 days prior to coronary artery bypass graft surgery, except in unstable or very high risk patients. Reducing the risk of bleeding has the potential to improve clinical outcomes, but it is important to ensure that strategies aimed at reducing the risk of bleeding do not compromise the net clinical benefit of clopidogrel that has been demonstrated in clinical trials. There is emerging evidence that bleeding is associated with an increased risk of recurrent ischaemic events and death, even when the bleeding is not severe enough to be considered life-threatening. Clopidogrel is an effective antiplatelet drug for preventing cardiovascular events and death but also increases the risk of bleeding.
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