Future Perspectives for Optimizing Oral Antiplatelet Therapy

Abstract

Secondary prevention of stroke and other manifestations of atherothrombosis is essential if the burden of disease associated with these events is to be reduced. Therefore, it is important to identify patients most likely to benefit from antiplatelet therapy. There is a good rationale for combining antiplatelet agents with different modes of action, since different signalling pathways contribute to platelet activation. Based on the promising results obtained with an adenosine diphosphate receptor antagonist-aspirin combination in coronary stenting, several additional trials with clopidogrel plus aspirin are ongoing. They include CURE (Clopidogrel in Unstable angina to prevent Recurrent Events, in unstable angina and non-Q-wave myocardial infarction) and COMMIT (in acute myocardial infarction), which compare clopidogrel with placebo in patients receiving aspirin, and CREDO (Clopidogrel for Reduction of Events During extended Observation), a 1-year treatment follow-up to the clopidogrel arms of the CLASSICS trial (Clopidogrel Aspirin Stent International Cooperative Study). Planned trials with clopidogrel in neurology include SPS3 (Secondary Prevention of Small Subcortical Strokes, in patients with symptomatic lacunar stroke), and MATCH (Management of Atherothrombosis with Clopidogrel in High-risk patients, in patients with stroke or transient ischaemic attack plus one additional risk factor), which will compare the efficacy of clopidogrel plus aspirin versus clopidogrel in reducing important ischaemic events. Combination therapy with an oral glycoprotein (GP) IIb/IIIa receptor antagonist plus aspirin has so far been less promising. Trials of three compounds – orbofiban, xemilofiban and sibrafiban – in combination with aspirin for secondary prevention in cardiac patients have reported increased mortality compared with aspirin alone. A similar effect was seen when sibrafiban monotherapy was compared directly with aspirin alone. Trials of newer oral GP IIb/IIIa inhibitors are under way or are planned. The combination of dipyridamole plus aspirin appears to be superior to aspirin alone for the prevention of stroke in patients with stroke or transient ischaemic attack; the effectiveness of this combination is being further investigated in ESPRIT (European/Australian Stroke Prevention in Reversible Ischaemia Trial).

The Effect of Combined Clopidogrel and Aspirin Therapy after Off-Pump Coronary Surgery

“…15 The Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events 13 and the Clopidogrel for Reduction of Events During Observation Trials randomized more than 10,000 patients to determine whether combined therapy with clopidogrel and aspirin is more effective than aspirin alone. 16 Clopidogrel was shown in the Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events study to be a safe and efficacious medication for the secondary prevention of vascular events and to result in few bleeding complications. 11 Clopidogrel with or without aspirin has been suggested to be superior to aspirin alone for the post-CABG prevention of ischemic events.…”

Impact of Postgraduate Medical Education on Recognition of Stroke

“…1 Also, there has been under-utilization of primary prevention strategies for stroke, including prophylactic administration of antiplatelet aggregation drugs, anticoagulation for atrial fibrillation, as well as carotid endarterectomy. [1][2][3][4][5][6][7][8][9][10] …”

The selection of antithrombotic agents in the prevention of recurrent ischemic stroke

“…Combined therapy with dipyridamole and warfarin, extended-release dipyridamole plus low-dose aspirin, and aspirin plus clopidogrel are safe and effective therapies for inhibition of thrombosis and prevention of stroke [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36]. It is not clear what the difference between the latter two might be in terms of reason for choosing one over the other when antiplatelet therapy is indicated.…”