Treatment for a Heart Attack
Treatment options include:
- Anti-platelet medications to prevent formation of blood clots in the arteries
- Anti-coagulant medications to prevent growth of blood clots in the arteries
- Clot-dissolving medications to open blocked arteries
- Supplemental oxygen to increase the supply of oxygen to the heart's muscle
- Medications to decrease the need for oxygen by the heart's muscle
- Medications to prevent abnormal heart rhythms
- Coronary Angioplasty with or without stent placement
The primary goal of treatment is to quickly open the blocked artery and restore blood flow to the heart muscle, a process called reperfusion. Once the artery is open, damage to heart muscle ceases, and the patient becomes pain free. By minimizing the extent of heart muscle damage, early reperfusion preserves the pumping function of the heart. Patients have the best outcomes if the artery can be reopened within four to six hours of a heart attack. Any delay can result in more widespread damage to heart muscle and a greater reduction in the ability of the heart to pump blood. Patients with hearts that are unable to pump sufficient blood develop heart failure, decreased ability to exercise, and abnormal heart rhythms. The amount of healthy heart muscle remaining after a heart attack is the most important determinant of the future quality of life and longevity.
Anti-platelet agents are medications that prevent blood clots from forming by inhibiting the aggregation of platelets. Platelets are fragments of cells that circulate in the blood. Platelets begin the formation of blood clots by clumping together (a process called aggregation). Platelet clumps are then strengthened and expanded by the action of clotting factors (coagulants) that result in the deposition of protein (fibrin) among the platelets. Aggregation of platelets occurs at the site of any injury or laceration, but it also occurs at the site of rupture of cholesterol plaques in the walls of coronary arteries. Formation of clots at the site of an injury or cut is a good thing because it prevents excessive loss of blood, but clots inside coronary arteries block the arteries and cause heart attacks.
There are three types of anti-platelet agents -- aspirin, thienopyridines and the glycoprotein IIb/IIIa inhibitors. These agents differ in their mode of action, anti-platelet potency, speed of onset of action and cost.
Aspirin inhibits the activity of the enzyme cyclo-oxygenase inside platelets. Cyclo-oxygenase is an enzyme whose activity is necessary for the formation of a chemical, thromboxane A2, that causes platelets to aggregate. Aspirin, by inhibiting the formation of thromboxane A2, which prevents platelets from aggregating and thereby prevents the formation of blood clots.
Aspirin alone has its greatest impact on improving survival among patients with heart attacks. Numerous studies have shown that aspirin reduces mortality (by 25%) when given to patients with heart attacks. Aspirin is easy to use, safe at the low doses used for anti-platelet action, fast acting (with an onset of action within 30 minutes), and cheap. Aspirin is given at a dose of 160 mg to 325 mg immediately to almost all patients as soon as a heart attack is recognized. It also is continued on a daily basis indefinitely after the heart attack. The only reason for not using aspirin is a history of intolerance or allergy to aspirin.
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).
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.
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 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.
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 (under the skin) 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.
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 injection.
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).
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, its 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.
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 six 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.)
Nitroglycerin is the most common nitrate used in the treatment of heart attacks. It can be given sublingually (under the tongue), as a spray, as a paste applied over skin, and intravenously. Intravenous nitroglycerine has a rapid onset of action and is commonly used in the initial (first 48 hours) treatment of heart attacks. Nitroglycerine is a vasodilator (blood vessel dilator), which opens arteries by relaxing the muscular wall of the artery. Nitroglycerine dilates coronary arteries as well as other blood vessels throughout the body. By dilating blood vessels, nitroglycerine lowers blood pressure, decreases the work that the heart must do, lowers the demand by the heart for oxygen, prevents coronary artery spasm, improves blood flow to the heart muscle, and potentially minimizes the size of the heart attack. Nitroglycerine is especially helpful in patients with heart attacks who also have heart failure or high blood pressure.
Angiotensin converting enzyme inhibitors
Angiotensin converting enzyme (ACE) inhibitors, another class of blood vessel dilators, often are given orally after a large heart attack to improve the healing of heart muscle. Examples of ACE inhibitors include captopril (Capoten), enalapril (Vasotec), lisinopril (Zestril and Prinivil), and ramipril (Altace). These medications lower the blood pressure and reduce the workload of the heart, thereby helping the damaged heart muscle to recover. They are especially helpful in patients who have recovered from heart attacks but have high blood pressure, heart failure, major damage to the left ventricle, and diabetes mellitus.
Beta-blockers such as propranolol (Inderal), metoprolol (Lopressor, Toprol XL), andatenolol (Tenormin) usually are given early during a heart attack and are continued long-term. Beta blockers antagonize the action of adrenaline and relieve stress on the muscles of the heart. Beta-blockers decrease the workload of the heart by slowing the heart rate and decreasing the force of contraction of heart muscle. Decreasing the workload decreases the demand for oxygen by the heart and limits the amount of damage to the heart muscle. Long-term administration of beta-blockers following a heart attack has been shown to improve survival and reduce the risk of future heart attacks. Beta-blockers also improve survival among patients with heart attacks by decreasing the incidence of life-threatening abnormal heart rhythms, for example, ventricular fibrillation. Beta-blockers can be given intravenously in the hospital and then can be taken orally for long-term treatment.
The side effects of beta-blockers are wheezing (worsening of breathing in patients with asthma), abnormally slow heart rate, and exacerbation of heart failure (especially in patients with significant damage to their heart muscle); however, in patients with chronic heart failure, beta blockers have recently been demonstrated to be helpful in decreasing symptoms and prolonging life.
Oxygen also is commonly administered during the acute phase of a heart attack as are narcotics such as morphine; these agents aid in the reduction of discomfort and actually help minimize the amount of heart damage.