Clinical trials antiplatelet therapy

Warfarin has not been adequately studied in non-cardioembolic stroke, but it is often recommended in patients after antiplatelet agents fail. One small retrospective study suggests that warfarin is better than aspirin.30 More recent clinical trials have not found oral anticoagulation in those patients without atrial fibrillation or carotid stenosis to be better than antiplatelet therapy. In the majority of patients without atrial fibrillation, antiplatelet therapy is recommended over warfarin. In patients with atrial fibrillation, long-term anticoagulation with warfarin is recommended and is effective in both primary and secondary prevention of stroke.12 The goal International Normalized Ratio (INR) for this indication is 2 to 3. 

The reported incidence of resistance to these drugs varies greatly, from less than 5% to 75%. In part this tremendous variation in incidence reflects the definition of resistance (recurrent thrombosis while on antiplatelet therapy vs in vitro testing), methods by which drug response is measured, and patient compliance. Several methods for testing aspirin and clopidogrel resistance in vitro are now FDA-approved however, their utility outside of clinical trials remains controversial. 

Rezkalla SH, Benz M. Antiplatelet therapy from clinical trials to clinical practice. Clin Med Res. 2003 1 101-104. 

Patients with acute coronary syndromes such as acute myocardial infarction and unstable angina remain at risk for recurrent myocardial ischemia despite therapy with antiplatelet agents and heparin. Although first clinical trials indicate a possible use of oral direct TIs for the prevention of cardiovascular events in patients after acute myocardial infarction, the presently available data are still limited and it has not... 

In summary, aspirin is beneficial in a large number of patients at high risk of occlusive cardiovascular disease. The recently reported large meta-analysis of antiplatelet therapy clinical trials suggests risk reduction associated with long term aspirin administration is independent of age, sex, and cardiovascular risk fiictors (44). 

Antiplatelet therapy protects at risk patients against stroke, myocardial infarction or death. A meta-analysis of 145 clinical trials of prolonged... 

More recently, Tran and Anand conducted a systematic review of the literature in an effort to summarize the best evidence for oral antiplatelet therapy in patients with cerebrovascular disease, CAD, and PAD. This review included 111 trials (42 of which included patients with PAD, n = 9214) and concluded that patients with PAD should use ASA (160 to 325 mg/day) or clopidogrel (75 mg/day) when ASA is not tolerated or contraindicated. This is in concordance with the recommendations of the Seventh American College of Chest Physicians (ACCP) Conference on Antithrombotic and Thrombolytic Therapy which recommends lifelong ASA (75 to 325 mg/day) over clopidogrel, ticlopidine, and no antithrombotic therapy in patients with PAD. Unfortunately, no data are currently avaUable from large, clinical, randomized trials that ASA, or any other antiplatelet therapies, can actually prevent or delay the progression of PAD. ... 

Antiplatelets are the mainstay of treatment for acute coronary syndrome (ACS), a spectrum of ischemic events that include myocardial infarction and unstable angina, with well-established benefit in preventing atherothrombosis. Results of a meta-analysis of 145 clinical studies reported a 25% reduction of atherothrombotic events in high-risk patients treated with antiplatelet therapy [12]. Another meta-analysis of 109 clinical trials has concluded that antiplatelet medications were able to reduce transient ischemic attacks and strokes by 22%, reduce coronary artery disease by 29%, and reduce peripheral artery disease by 23% [13]. Table 19.1 summarizes the major commercially available antiplatelet agents. 

Anonymous (1994) Collaborative overview of randomised trials of antiplatelet therapy—1 prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists Collaboration. British Medical Journal (Clinical Research Edition) 308 (6921), 81-106. 

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