Heparin. Heparin prevents the formation and growth of blood clots by inhibiting the action of clotting factors that cement the clumps of platelets together. Heparin is given either intravenously or as a subcutaneous (under the skin) injection.

Heparin commonly is given intravenously, usually with aspirin, anti-platelet agents, or fibrinolytic (clot-dissolving) medications for treating heart attacks. Intravenous heparin is given (usually with aspirin or an anti-platelet agent) to patients with heart attacks who are undergoing PTCA with or without stenting.

Heparin also is given to patients who are at risk of developing blood clots within the chambers (atria and ventricles) of the heart. (For example, patients with atrial fibrillation can develop blood clots in the atria. Patients with large heart attacks and major damage to the heart muscle also can develop blood clots in the ventricles.) Heparin’s anti-coagulant effect is fast acting (beginning shortly after the start of the infusion) and dose-related (greater with higher doses). The duration of heparin treatment for heart attacks is approximately 48 hours.

Heparin’s major side effect is bleeding, and the most serious bleeding complication is intracranial hemorrhage (bleeding into the brain). The risk of bleeding is higher with higher doses. Thus, patients receiving heparin will undergo frequent blood testing to measure APPT levels. The APPT level is a measure of the degree of anti-coagulation. The goal is to keep the patient’s APPT level in a safe range and to avoid abnormally high APPT levels that signify excessive anti-coagulation and a greater risk of bleeding. If there is bleeding, heparin has the advantage of having a short duration of action, and its anti-coagulant effects disappears rapidly after stopping the intravenous infusion.

Low molecular weight heparin. Low molecular weight heparins such as enoxaparin (Lovenox) and dalteparin (Fragmin), are sub-fractions of heparin with longer-lasting effects than heparin. They can be given every 12-24 hours as subcutaneous injections (like insulin). Studies have shown enoxaparin and dalteparin to be equivalent to intravenous heparin in patients with many conditions such as heart attacks, unstable angina, and blood clots in the veins or arteries of the lungs. The effects of low molecular weight heparins generally wear off after 6-12 hours. They are not used in place of intravenous heparin in patients undergoing PTCA or stenting.

Warfarin. Warfarin (Coumadin) prevents the formation of blood clots by inhibiting the production of clotting factors by the liver. Warfarin must be taken orally and is slow acting; it can take days to achieve an adequate anti-coagulant effect. Warfarin’s anti-coagulant effect is dose-related, that is, it’s effect is greater with larger doses.

Because of its slow onset of action, Coumadin is not commonly used immediately for the treatment of heart attacks. Instead, it is used orally on a long-term basis in selected patients after heart attacks to prevent blood clots. For example, patients with atrial fibrillation or patients with major damage to ventricular muscle will take warfarin daily on a long-term basis to prevent blood clots in the atria and ventricles, respectively. Warfarin also is commonly used to prevent blood clots in veins of the legs in patients who are likely to develop them.

The risk with warfarin is abnormal bleeding, and the risk of bleeding is higher with higher doses. Thus, patients on warfarin should have their blood tested frequently (often weekly) to measure their prothrombin time and INR. Like APPT, the prothrombin time and INR measure the degree of anti-coagulation. The goal of treatment is to keep the prothrombin time and INR in a safe range, avoiding excessively high prothrombin time and INR levels that indicate too much anti-coagulation and a greater risk of bleeding. The effects of warfarin may be increased or decreased greatly by many other medications or foods, and it is crucial to review these medications and foods with the doctor.

Warfarin has a long duration of action, and it’s anti-coagulation effect can last several days after it is stopped. Therefore, transfusions of clotting factors and/or vitamin K (to stimulate the liver to produce the clotting factors depleted by treatment with warfarin) must be given to reverse the anti-coagulation in the event of serious bleeding.

Clot-dissolving drugs

While anti-platelet agents and anti-coagulants prevent the formation of blood clots, they cannot dissolve existing blood clots and hence cannot be relied upon to open blocked arteries rapidly. Clot-dissolving drugs (also called fibrinolytic or thrombolytic medications) actually dissolve blood clots and can rapidly open blocked arteries. Intravenous administration of clot-dissolving drugs such as tissue plasminogen activator (TPA) or TNK can open up to 80% of acutely blocked coronary arteries. The earlier these drugs are administered, the greater the success at opening the artery and the more effective the preservation of heart muscle. If clot-dissolving drugs are given too late (more than 6 hours after the onset of the heart attack), most of the muscle damage already may have occurred.

If a hospital does not have a catheterization laboratory with the ability to perform PTCA, or if there are logistic reasons why PTCA will be delayed, clot-dissolving drugs can be promptly administered to achieve reperfusion. PTCA then may be performed in patients who fail to respond to the clot-dissolving drugs. (If prompt PTCA and stenting are available, it has been demonstrated that they are preferable to clot-dissolving drugs to open arteries.)

Clot-dissolving drugs increase the risk of bleeding enough so that some patients cannot be treated with them, for example, patients with recent surgery or major trauma, recent stroke, bleeding ulcer, or other conditions that increases the risk of bleeding.

Coronary angiography and percutaneous transluminal coronary angioplasty

Coronary angiography and percutaneous transluminal coronary angioplasty (PTCA) is the most direct method of opening a blocked coronary artery. The procedures are performed in the catheterization laboratory in a hospital. Under x-ray guidance, a tiny plastic catheter with a balloon on its end is advanced over a guide wire from a vein in the groin or the arm and into the blocked coronary artery. Once the balloon reaches the blockage, it is inflated, pushing the clot and plaque out of the way to open the artery. PTCA can be effective in opening up to 95% of arteries. In addition, the angiogram (x-ray pictures taken of the coronary arteries) allows evaluation of the status of the other coronary arteries so that long-term treatment plans may be formulated.