Aspirin is taken daily following a heart attack to reduce the risk of another heart attack. (Preventing further heart attacks is called secondary prevention, while preventing the first heart attack is called primary prevention). The ideal daily dose of aspirin for secondary prevention has not been established. Some doctors recommend 160 mg; others recommend 81 mg.

The reason for this difference has to do with aspirin’s occasional long-term side effect of bleeding (for example from stomach ulcers). Even though the risk of major bleeding with long-term, moderate dose aspirin (325 mg/day) is low (less than 1%), this risk can be lowered slightly by using an even lower dose (160 or 81 mg/day).

Aspirin also benefits patients with forms of coronary heart disease other than an acute heart attack. Aspirin has been shown to reduce heart attacks and improve survival in the following patients:

 
• Aspirin improves survival among patients with unstable angina. Patients with unstable angina experience chest pains at rest or with minimal exertion. These patients have critically narrowed coronary arteries and are at imminent risk of having a heart attacks  
• Aspirin improves survival among patients with stable exertional angina. (These are patients who experience chest pain only with exertion.)  
• Aspirin prevents formation of blood clots at the site of the PTCA (see below).  
• Aspirin prevents the formation of blood clots that can occlude surgical bypass grafts. (Occlusion of bypass grafts can lead to heart attacks.)  
• Aspirin in low doses (81 mg/day) has been shown to prevent first heart attacks (primary prevention)

The thienopyridines

The thienopyridines such as ticlopidine (Ticlid) and clopidogrel (Plavix) inhibit the ADP receptor on the surface of platelets. Inhibiting the ADP receptors on the platelets prevent the platelets from aggregating and causing blood clots to form. The theinopyridines are more potent anti-platelet agents than aspirin. Clopidogrel (Plavix) is used far more commonly than ticlopidine (Ticlid) because ticlopidine can, in rare instances, cause low platelet and/or white blood cell counts. Clopidogrel plays an important role in the treatment of heart attacks and is used in the following situations:

 
• Clopidogrel is used instead of aspirin in patients who have an allergy to aspirin.  
• Clopidogrel often is given together with aspirin in treating heart attacks. Studies have shown that the combination of aspirin and clopidogrel is more effective than aspirin alone in improving survival and limiting damage to heart muscle among patients with heart attacks.  
• Clopidogrel is given together with aspirin to patients undergoing PTCA with or without coronary stenting (see later discussion). Studies have shown that the combination of aspirin and clopidogrel is more effective than aspirin alone in preventing formation of blood clots that can re-occlude the coronary artery unblocked by PTCA and in preventing blood clots within recently placed stents.  
• After a heart attack or after PTCA, aspirin is given indefinitely. The optimal duration of clopidogrel has not been established, and duration of use by physicians varies from weeks to months.

Patients who receive the combination of clopidogrel and aspirin are more likely than patients who receive aspirin alone to develop complications of major bleeding following coronary artery bypass surgery. Therefore, ideally clopidogrel should be stopped 3-7 days before surgery.

Glycoprotein IIb/IIIa inhibitors

The glycoprotein IIb/IIIa inhibitors such as abciximab (Reopro) and eptifibatide (Integrilin) prevent aggregation of platelets by inhibiting the glycoprotein receptors on the platelets. They are the most potent anti-platelet agents, approximately 9 times more potent than aspirin, and three times more potent than the thienopyridines. The glycoprotein IIb/IIIa inhibitors are also the most expensive anti-platelet agents. The currently FDA-approved glycoprotein IIb/IIIa inhibitors have to be given intravenously. They usually are given along with aspirin and heparin. They are quick acting; their maximal anti-platelet effects are achieved within minutes of infusion. These inhibitors have become important in the treatment of patients with heart attacks, patients with unstable angina, and patients undergoing PTCA with or without stenting. Numerous studies have shown that glycoprotein IIb/IIIa inhibitors:

 
• Decrease the size of the blood clot blocking the coronary arteries, thus improving blood flow, limiting damage to heart muscle, and improving survival among patients with heart attacks  
• Decrease the incidence of heart attacks and improve survival among patients with unstable angina  
• Prevent the formation of blood clots inside coronary stents and in coronary arteries unblocked by PTCA, thus decreasing the incidence of heart attacks and improving survival, specifically, when given intravenously at the time of PTCA and stenting and followed by oral aspirin and clopidogrel

The major risk of glycoprotein IIb/IIIa inhibitors is bleeding. Therefore, patients on heparin, aspirin, and glycoprotein IIb/IIIa inhibitors have to be monitored closely for bleeding. Recent studies have demonstrated equal efficacy of abciximab and eptifibatide. Eptifibatide is shorter acting than abciximab. In the event of major bleeding, the anti-platelet effect of eptifibatide can be reversed within hours of stopping the intravenous infusion, while the anti-platelet effect of abciximab will last much longer. Sometimes, transfusions of platelets are necessary to treat major bleeding due to abciximab.

An uncommon side effect of glycoprotein IIb/IIIa inhibitors is the development of low platelet counts (thrombocytopenia). Thrombocytopenia can increase the risk for bleeding and, in rare instances, may actually cause blood to clot. Thus, patients receiving glycoprotein IIb/IIIa inhibitors should have their platelet counts monitored closely.

Anti-coagulants

Coagulants (clotting factors) are proteins produced by the liver. Clotting factors are responsible for “cementing” clumps of platelets together to form a stronger and larger clot. Anti-coagulants such as intravenous or subcutaneous heparin, subcutaneous low molecular weight heparin, and oral warfarin (Coumadin), prevent the formation of blood clots either by inhibiting the production of clotting factors or by interfering with the action of the clotting factors.