Myocardial infarction antiplatelet agents

Gent M. A systematic overview of randomised trials of antiplatelet agents for the prevention of stroke, myocardial infarction and vascular death. In Hass WK, Easton ID, editors. Ticlo-pidine, platelets and vascular disease. New York Springer-Verlag 1993 p99-116. 

The AHA/ASA guidelines recommend that antiplatelet therapy as the cornerstone of antithrombotic therapy for the secondary prevention of ischemic stroke and should be used in noncardioembolic strokes. Aspirin, dopidogrel, and extended-release dipyridamole plus aspirin are all considered first-line antiplatelet agents (see Table 13-1). The combination of aspirin and clopido-grel can only be recommended in patients with ischemic stroke and a recent history of myocardial infarction or coronary stent placement and then only with ultra-low-dose aspirin to minimize bleeding risk. 

The FDA has approved the use of 325 mg/d for primary prophylaxis of myocardial infarction but urges caution in this use of aspirin by the general population except when prescribed as an adjunct to risk factor management by smoking cessation and lowering of blood cholesterol and blood pressure. Meta-analysis of many published trials of aspirin and other antiplatelet agents confirms the value of this intervention in the secondary prevention of vascular events among patients with a history of vascular events. 

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... 

The efficacy of clopidogrel as an antiplatelet agent in atherothrombotic disorders was demonstrated in the CAPRIE trial. In this study of more than 19,000 patients with a history of either myocardial infarction (MI), stroke, or peripheral arterial disease (PAD), clopidogrel 75 mg/day was compared with aspirin 325 mg/day for its ability to decrease MI, stroke, or cardiovascular death. In the final analysis, clopidogrel was slightly (8% relative risk reduction [RRR]) more effective than aspirin (p =. 043) and had a similar incidence of adverse effects. It is not associated with the blood dyscrasias (neutropenia) common with its congener, ticlopidine, and is used widely in patients with atherosclerosis. 

The selectivity of coxibs for COX-2 over COX-1 gives them antiinflammatory and antiproliferative actions with rednced G1 side effects, bnt it also makes them ineffective as antiplatelet agents and thns increases risks from myocardial infarction and stroke. 

Tirofiban Tiroflban (Aggrastat), a nonpeptide, small-molecule inhibitor of anePs, appears to have a similar mechanism of action as eptifibatide. Tiroflban has a short duration of action and has efficacy in non-Q-wave myocardial infarction and unstable angina. Reductions in death and myocardial infarction have been about 20% compared to placebo, results similar to those with eptifibatide. Side effects also are similar to those of eptifibatide. The agent is specific to anePs and does not react with the vitronectin receptor. Metaanalysis of trials using anePs inhibitors suggests that their value in antiplatelet therapy after acute myocardial infarction is limited. Tiroflban is administered intravenously at an initial rate of 0.4 pg/kg per minute for 30 minutes, and then continued at 0.1 mg/kg per minute for 12 to 24 hours after angioplasty or atherectomy. It is used in conjunction with heparin. 

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. 

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