Coronary Artery Disease and Angina

Description

Alternative Names

Anti-Clotting Medications

Anti-clotting agents that inhibit or break up blood clots are used at every stage of heart disease. They are generally either anti-platelet agents or anticoagulants. Investigators are also studying combinations of anti-clotting agents, which may be useful in patients with severe heart disease. All anti-clotting therapies carry the risk of bleeding, which can lead to dangerous situations, including stroke.

A thrombus is a blood clot that forms in a vessel and remains there. An embolism is a clot that travels from the site where it formed to another location in the body. Thrombi or emboli can lodge in a blood vessel and block the flow of blood in that location depriving tissues of normal blood flow and oxygen. This can result in damage, destruction (infarction), or even death of the tissues (necrosis) in that area.

Anti-platelet Drugs. These agents prevent formation of blood platelets. Platelets are very small disc-shaped blood cells that are important for blood-clotting .

• Aspirin. Aspirin is an antiplatelet agent. It is the most common anti-clotting drug. Nearly anyone with existing heart disease or at risk for it is advised to take a low-dose aspirin every day.
• Glycoprotein IIb/IIIa Inhibitors. These potent blood-thinning agents include abciximab (ReoPro, Centocor), eptifibatide (Integrilin), tirofiban (Aggrastat), and lamifiban. They are administered intravenously in the hospital and are being used after surgery angioplasty and stent placement. Other benefits are not yet clear.
• Thienopyrindines. Clopidogrel (Plavix) and ticlopidine (Ticlid) are potent oral platelet inhibitors.

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Anticoagulants. Anticoagulants help thin blood and include the following:

• Heparin. Standard, or unfractionated, heparin; Low-molecular weight heparin (LMWH), which include Enoxaparin (Lovenox), dalteparin (Fragmin), tinzaparin (Innohep).
• Warfarin (Coumadin).
• Direct thrombin inhibitors. They include argatroban (Novastan), danaproid (Orgaran), and lepirudin (Refludan).

Anti-Platelet Drugs

Aspirin. Aspirin is known as a nonsteroidal anti-inflammatory agent (NSAID). It inhibits blood platelets, which are major clotting factors, from sticking together to form a blood clot. A daily low-dose aspirin (75 to 160 mg) is usually the first choice for preventing heart disease in high-risk individuals. It is proving to prevent heart attacks and death in people with existing heart disease and a history of heart attack. Aspirin alone has been reported to reduce risk of death from heart attack by 25% to 50%, at least in men. (Whether it has significant heart benefits for women is less clear.) It also reduces the risk for stroke.

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Side effects for anyone from prolonged use of aspirin may include gastrointestinal ulcers and bleeding. (There may be a slight increased risk for bleeding-related strokes, which are very uncommon, however. Furthermore, this risk may be outweighed by protection against the more common stroke, which is caused by artery blockage.)

Of great concern is research suggesting certain interactions that might reduce the benefits of aspirin or other heart protective drugs. One 2000 report suggested that taking ibuprofen (Advil) right before taking an aspirin may inhibit aspirin's benefits on the heart. Both are drugs known as NSAIDs. Some studies suggest that both these NSAIDs along with others, such as naproxen (Aleve), interfere with diuretics and ACE inhibitors. Recent use of NSAIDs, in fact, has been associated with a higher risk of hospitalization in heart failure patients, especially those taking diuretics or ACE inhibitors. An encouraging 2003 analysis, however, reported that ACE inhibitors still significantly reduced risks for adverse heart events, including hospitalizations for heart failure, regardless of whether or not the patients were also taking aspirin.

Clopidogrel and Other Thienopyrindines. Clopidogrel (Plavix, Iscover) is an oral platelet inhibitor called a thienopyrindine. When taken with aspirin, this agent is proving to significantly reduce the risk for heart attack and stroke in patients with acute coronary artery syndrome (unstable angina or early signs of heart attack). Clopidogrel is also recommended for patients who are undergoing angioplasty. If possible, however, it should be delayed for at least five days in patients undergoing bypass surgery because of a significant bleeding risk.

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Ticlopidine (Ticlid) is another effective thienopyrindine, but has largely been replaced by clopidogrel because of dangerous blood disorders, particularly thrombocytopenia.

Glycoprotein IIb/IIIa Inhibitors. Glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors are potent drugs that thin blood by blocking platelets (clotting factors in the blood). They are administered intravenously and include abciximab (ReoPro, Centocor), eptifibatide (Integrilin), tirofiban (Aggrastat), and lamifiban. GPIIb/IIIa inhibitors are used for acute coronary syndrome (ACS), not for management of day-to-day angina. Studies on their benefits have been mixed, depending on how they are used. Evidence suggest their use in the following situations:

• These agents are very beneficial when used with angioplasty and coronary stent placement in patients with acute coronary artery syndromes (ACS). They may be most effective in such cases if administered during angioplasty, rather than beforehand.

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• Early use of these drugs in the emergency room appears to benefit selected patients with high-risk ACS (such as those who have high levels of troponins--markers of heart damage).

As in heparin there is a risk for thrombocytopenia, a drastic reduction in platelets that can cause severe bleeding. Certain patients at highest risk for this complication are thin, elderly, nonwhite, and have more than one heart risk factor.

Note: Oral GPIIb/IIIa inhibitors (called super-aspirins) have been under investigation but many were withdrawn after reports of significantly high mortality rates.

Anticoagulants

Anticoagulants are drugs that prevent or delay blood coagulation and the formation of blood clots. Heparin has been the standard anticoagulant, but a number of agents are now available that are proving to be better choices in many cases.

Standard (Unfractionated) Heparin. The heparin referred to as unfractionated heparin has been the standard for year, used alone or in combination with aspirin for managing unstable angina. It is no longer the recommended first choice, however, for this patient group. It must be intravenously administered and monitored with frequent blood tests. The major complication is thrombocytopenia (a severe drop in platelets). This condition is extremely serious and can become life-threatening, particularly with bleeding in various body tissues. Alternatives include low-molecular weight heparin and direct thrombin inhibitors.

Low-Molecular Weight Heparin. Enoxaparin (Lovenox), dalteparin (Fragmin), tinzaparin (Innohep) are drugs known as low-molecular weight heparins (LMWHs). Many physicians now recommend these agents over standard heparin for patients with unstable angina (unless bypass surgery is being planned). They have similar rates of survival, recurring angina, and bleeding as standard heparin. However, they appear to pose lower risks for heart attack, repeat angioplasties, and thrombocytopenia. They require injections but do not require the ongoing monitoring that standard heparin does. Patients may even be able to self-administer LMWHs as people with diabetes do insulin.

Warfarin. Warfarin (Coumadin) is an oral anticoagulant. It prevents clots by inhibiting vitamin K. Warfarin is used with aspirin after a heart attack to prevent another one and to prevent blood clots in patients with atrial fibrillation. Warfarin is also proving to be more effective than aspirin for preventing heart attacks in patients with acute coronary syndromes. There is even some evidence that it might prevent disease progression itself in the arteries of the heart. Warfarin therapy must be monitored with frequent blood tests. In one study, bleeding occurred in 1% of patients taking aspirin or warfarin alone and in 2% taking a combination.

Direct Thrombin Inhibitors (DTIs). Direct thrombin inhibitors are a more recent group of anti-coagulants. The first DTI hirudin, a natural substance derived from the saliva of leeches. New forms include argatroban (Novastan), bivalirudin (Angiomax), danaproid (Orgaran), lepirudin (Refludan), desirudin (Revasc), inogatran, and efegatran. Ximelagatran (Exanta) is a new oral DTI that may prove to be specifically effective. Many of these agents used along with warfarin are proving to be good options for patients who develop thrombocytopenia with heparin use. DTIs may prove to be superior to standard heparin for patients with acute coronary syndrome.