Coronary artery disease - Medications

Medications:

Anti-Platelet and Anticoagulant Drugs

Anti-clotting drugs that inhibit or break up blood clots are used at every stage of heart disease. They are generally classified as either anti-platelets or anticoagulants. 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.

Aspirin. Aspirin is known as a nonsteroidal anti-inflammatory drug (NSAID). It stops blood platelets, which are major clotting factors, from sticking together to form a blood clot. Aspirin therapy is extremely beneficial for patients with coronary artery disease, peripheral artery disease, or history of stroke.

A daily low-dose aspirin (75 - 81 mg) is usually the first choice for preventing heart disease in high-risk individuals. Aspirin can reduce the risk of heart attack and ischemic stroke. However, prolonged use of aspirin can increase the risks for stomach bleeding. A doctor needs to consider a patient� ' s overall medical condition and risk factors for heart attack before recommending aspirin therapy.

In general, daily aspirin is recommended for prevention of heart disease for the following people who have never had a heart attack or stroke:

• Women age 55 to 79. (Women who are younger than age 55 should not take aspirin for primary prevention.)
• Men age 45 to 79 years should take aspirin if the chances for preventing stroke or heart attack outweigh the risks of gastrointestinal bleeding. Men younger than age 45 should not take aspirin for primary prevention.
• For women and men age 80 years or older, it is not clear if the benefits of aspirin for heart protection outweigh the risks for bleeding.

Clopidogrel. Clopidogrel (Plavix) is an anti-platelet drug known as a thienopyridine. For most patients, the addition of Clopidogrel to aspirin for the prevention of heart disease is not recommended, as it adds no significant benefit, adds significantly to the cost, and increases the risk of bleeding. It may be used in place of aspirin for patients who are aspirin allergic or who cannot tolerate aspirin.

When taken with aspirin, clopidogrel is recommended for patients with acute coronary syndrome (unstable angina or early signs of heart attack) or those who have had a drug-eluting stent inserted. According to the American Heart Association, patients who have a drug-eluting stent must take both aspirin and a thienopyridine for at least 1 year after the stent is inserted.

Clopidogrel is also recommended for patients who are undergoing angioplasty. Patients having coronary bypass surgery should not take clopidogrel forat least 5 - 7 days prior to surgery because of a significant bleeding risk. Researchers are investigating whether clopidogrel and aspirin together are better than aspirin alone in reducing the risks following coronary bypass surgery.

Warfarin and Anticoagulants. Anticoagulants are drugs that prevent or delay blood coagulation and the formation of blood clots. Warfarin (Coumadin) is an oral anticoagulant. It prevents clots by inhibiting vitamin K. Warfarin is used for patients with certain types of prosthetic heart valves and to prevent blood clots in patients with atrial fibrillation. Warfarin therapy poses a dangerous risk for bleeding, and blood coagulation must be monitored with frequent blood tests. A third of all people are genetically predisposed to a higher bleeding risk with warfarin. A genetic test can help doctors determine which patients may be especially sensitive to this drug.

Beta Blockers

Beta blockers are useful for preventing angina attacks and reducing high blood pressure. They reduce the heart's oxygen demand by slowing the heart rate and lowering blood pressure. They can help reduce risk of death from heart disease and from heart surgeries, including angiography and coronary bypass.

Beta blockers are used or recommended in a number of situations:

• They are started in nearly all patients who have just had a heart attack or acute coronary syndrome.
• They are the drugs of choice for older patients with stable angina and may also be beneficial for people with silent ischemia. They are less useful for the treatment of Prinzmetal� ' s angina.
• They may be used alone or with other medications for management of rhythm disturbances or high blood pressure.

Beta blockers include propranolol (Inderal), carvedilol (Coreg), bisoprolol (Zebeta), acebutolol (Sectral), atenolol (Tenormin), labetalol (Normodyne, Trandate), metoprolol (Lopressor, Toprol-XL), and esmolol (Brevibloc). A nasal spray form of propranolol appears to be very helpful in reducing exercise-induced angina attacks.

Side Effects. Beta blocker side effects include fatigue, lethargy, vivid dreams and nightmares, depression, memory loss, and dizziness. They can lower HDL (“good”) cholesterol. Beta blockers are categorized as non-selective or selective. Non-selective beta blockers, such as carvedilol and propranolol, can narrow bronchial airways. These beta blockers should not be used by patients with asthma, emphysema, or chronic bronchitis.

PATIENTS SHOULD NEVER ABRUPTLY STOP TAKING THESE DRUGS. The sudden withdrawal of beta blockers can rapidly increase heart rate and blood pressure. The doctor may advise a patient to slowly decrease the dose before stopping completely.

Angiotensin Converting Enzyme (ACE) Inhibitors

Angiotensin converting enzyme (ACE) inhibitors are important heart-protective drugs, particularly for people with diabetes and high blood pressure. They reduce the production of angiotensin, a chemical that causes arteries to narrow, and so are commonly used to lower blood pressure. They may also reduce risk for heart attack, stroke, complications of diabetes, and death in patients at high risk for heart disease.

ACE inhibitors are indicated for most patients with coronary artery disease or any other vascular diseases, such as peripheral vascular disease. They are particularly helpful for patients with coronary artery disease who also have diabetes or who have left ventricular dysfunction (when the heart's main chamber does not pump as well as it should).

ACE inhibitors include captopril (Capoten), ramipril (Altace), enalapril (Vasotec), quinapril (Accupril), benazepril (Lotensin), perindopril (Aceon), and lisinopril (Prinivil, Zestril).

Side Effects. Side effects of ACE inhibitors may include an irritating cough. More serious side effects are uncommon but may include excessive drops in blood pressure, allergic reactions, and high blood potassium levels. [For more information, see In-Depth Report #14: High blood pressure.]

Nitrates

Nitrates have been used in the treatment of angina for over 100 years. These drugs release nitric oxide, thereby relaxing the smooth muscles in blood vessels. Nitrates are used primarily for control of angina symptoms. Many nitrate preparations are available. The most commonly used are nitroglycerin, isosorbide dinitrate, and isosorbide mononitrate. Nitrates can be absorbed from the gastrointestinal tract (oral tablet), skin (ointment or patch), or from under the tongue (sublingual tablet or spray).

Rapid Acting Nitrates. Rapid-acting nitrates are used to treat acute attacks. Nitroglycerin is the most widely used drug for this purpose. It can be administered under the tongue (sublingually or as a spray) or pocketed between the upper lip and gum (buccally) and can relieve angina within minutes. The procedure for taking nitroglycerin during an attack is as follows:

• At the onset of an angina attack, the patient administers one sublingual or buccal tablet or one metered dose of the spray.
• If the pain is not relieved within 5 minutes the patient takes a second dose; a third can be taken after another 5 minutes if symptoms persist.
• If pain continues after a total of three doses in 15 minutes, the patient should go immediately to the nearest emergency room.

Nitroglycerin is very unstable so its potency can be easily lost. Patients should take the following precautions:

• Keep no more than 100 tablets on hand, stored in their original container.
• When first opened, the cotton filler should be discarded, and the cap screwed on tightly immediately after each use.
• A supply should always be kept close at hand in case of an attack, with the rest kept in a cool dry place.

Intermediate to Long-Term Nitrates. Sublingual tablets of isosorbide dinitrate have a slower onset of action than nitroglycerin and are useful for preventing exercise angina. Ointments, patches, and oral tablets are used for longer-term prevention of angina attacks:

• Transdermal patches are applied in the morning to any hair- or injury-free area on the chest, back, stomach, thigh, or upper arm. Hands should be washed after each patch or ointment application, and sites of application should be rotated to avoid skin irritation.
• Nitroglycerin ointment is applied by measuring out an even amount on an applicator paper and then placing, not rubbing or massaging, it on the chest, stomach, or thigh. Any ointment that remains from the previous application should be removed.

Long-acting forms may lose their effectiveness over time, so doctors generally schedule nitrate-free breaks to prevent tolerance.

Side Effects. Nitrates can have many side effects, some of which can be serious.

Common side effects of nitrates include headaches, dizziness, nausea and vomiting, blurred vision, fast heartbeat, sweating, and flushing on the face and neck. Low blood pressure and dizziness can be relieved by lying down with the legs elevated. These effects are significantly worsened by alcohol, beta blockers, calcium channel blockers, and certain antidepressants. Patients who take nitrates in any form cannot take medications for erectile dysfunction, such as sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). The doctor may prescribe medicines to lessen these side effects. Patients should contact their doctor if these side effects are persistent or severe.

Serious side effects requiring immediate medical help include fever, joint or chest pain, sore throat, skin rash (especially on the face), unusual bleeding or bruising, weight gain, and swelling of the ankles.

Withdrawal. Withdrawal from nitrates should be gradual. Abrupt termination may cause angina attacks.

Calcium Channel Blockers (CCBs)

Calcium channel blockers reduce heart rate and slightly dilate the blood vessels of the heart, thereby decreasing oxygen demand and increasing oxygen supply. They also reduce blood pressure. CCBs vary chemically, however, and although some are helpful, others may even be dangerous for certain patients with angina.

• Long-acting nifedipine (Adalat, Procardia) and nisoldipine (Sular) and newer CCBs, such as amlodipine (Norvasc) and nicardipine (Cardene), may be beneficial for some patients with angina. They can be considered alone for patients who cannot tolerate beta blockers, but may provide the best results when used in combination with a beta blocker. Studies suggest that they reduce the need for repeat angioplasties. Their effects on other outcomes, including mortality rates and heart attack, are less clear.
• Short-acting CCBs, including short-acting forms of verapamil, diltiazem, nifedipine, and nicardipine, are helpful for many patients with Prinzmetal's angina. However, short-acting forms of certain CCBs, such as nifedipine and nisoldipine, have been associated with severe and even dangerous side effects, including an increase in heart attacks and sudden death in some patients with unstable angina. They also increase the risk for adverse effects in patients with stable angina. Short-acting CCBs are, therefore, not used for stable or unstable angina.

There is no strong evidence that any calcium channel blockers improve survival rates. Overdose can cause dangerously low blood pressure and slow heart beats. Patients with heart failure have a higher risk for death with these drugs and should not take them. No one taking any calcium channel blocker should withdraw abruptly because such action could dangerously increase the risk of high blood pressure. Note: Grapefruit and Seville oranges boost the effects of CCBs, sometimes to toxic levels. (Regular oranges do not appear to pose any hazard.)

Other Drugs

Ranolazine (Ranexa) is used to treat chronic angina in patients who have not responded to other angina drugs. Ranolazine is taken in combination with amlodipine, beta blockers, or nitrates.