Drug therapy is effective for the treatment of stable angina and for slowing progression of coronary artery disease. Unstable angina may require surgical intervention in addition to the therapies given for stable angina.

Nitrates

Nitrates have been used in the treatment of angina for over a hundred years. These drugs release nitric oxide, therapy relaxing the smooth muscles in blood vessels. Many nitrate preparations are available; the most commonly used are nitroglycerin, isosorbide dinitrate, and isosorbide mononitrate. Erythrityl is popular overseas but is prescribed less in the US. Nitrates can be absorbed rapidly from the gastrointestinal tract (oral tablet), skin (ointment or patch), and from under the tongue (sublingual tablet or spray). Rapid-acting nitrates are used to treat acute attacks, whereas intermediate- and slow-acting nitrates are used to prevent angina. Nitroglycerin is the most widely used rapid-acting nitrate and can relieve angina within minutes. Sublingual nitroglycerin tablets are popular preparations for angina attacks and to prevent exercise-induced angina. Sublingual tablets of isosorbide dinitrate and erythrityl have a somewhat slower onset of action. If the pain is not relieved within five minutes after the first tablet, a second pill is placed under the tongue, and a third pill can be taken after another five minutes if symptoms persist. If pain continues, the patient should go to the nearest emergency room at once. A sublingual nitroglycerine spray is also available and may be more stable than the tablet. Nitroglycerin is also available as a buccal tablet, which is placed between the upper lip and gum. Ointments, patches, and oral tablets are used for longer-term prevention of angina attacks.

Nitroglycerin is very volatile so its potency can be easily lost. A patient should 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. 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. 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.

Long-acting forms may lose their effectiveness over time, so physicians generally schedule nitrate-free breaks to prevent tolerance. The use of drugs known as ACE inhibitors, normally used for high blood pressure, may help prevent tolerance to nitrates. (Some studies suggest that vitamin C or E might also help prevent tolerance.) Some concern exists that nitrate-free periods might increase the risk for angina and adverse heart events, although one large study found no danger in those using intermittent transdermal nitroglycerine. Side effects of nitrates include headaches, dizziness, nausea, blurred vision, fast heartbeat, and sweating. Low blood pressure and dizziness can be relieved by lying down with the legs elevated; these effects can be significantly worsened by alcohol, beta-blockers, calcium channel blockers, and certain antidepressants. Withdrawal from nitrates should be gradual; abrupt termination may cause angina attacks.

Beta-Blockers

Beta-blockers reduce the oxygen demand of the heart by slowing the heart rate and lowering arterial pressure. Such drugs include propranolol (Inderal), labetalol (Normodyne, Trandate), acebutolol (Sectral), atenolol (Tenormin), metoprolol (Toprol), and bisoprolol (Zebeta). They are now well known for reducing deaths from heart disease. They are equally effective to calcium channel blockers and have fewer adverse events (see below). Carvedilol (Coreg), a newer drug known as a nonselective beta-blocker, appears to be as safe as the older beta-blockers and may prove to have additional advantages. Beta-blockers do not stop angina attacks, but, used preventively, they reduce their frequency and the dependency on nitrates. A nasal spray form of propranolol appears to be very beneficial in helping to reduce exercise-induced angina attacks. Beta-blockers may also be beneficial for people with silent ischemia. They are less useful for the treatment of Prinzmetal's angina. As with all drugs, patients should discuss adverse effects and drug interactions with their physicians. Beta-blockers should never be discontinued abruptly as this can result in adverse cardiovascular consequences.

Calcium Channel Blockers

Calcium channel blockers reduce heart rate and slightly dilate the blood vessels of the heart, thereby decreasing oxygen demand and increasing oxygen supply. They include verapamil (Calan, Isoptin), nicardipine (Cardene), amlodipine (Norvasc), diltiazem (Cardizem, Tiazac), nifedipine (Adalat, Procardia), and felodipine. They are helpful in reducing angina attacks and some may reduce the need for nitrates. Calcium channel blockers may be particularly beneficial in combination with nitrates for patients with Prinzmetal's variant angina. There is no evidence, however, that calcium channel blockers increase survival rates, and major studies indicate that the less expensive beta-blockers are at least as if not more effective than calcium channel blockers and have fewer adverse effects. (The combination of these two drugs is very effective in treating exercise-induced stable angina but some studies have reported that used together, they cause a high incidence of dizziness.) There have been insufficient studies to determine how they compare with nitrates. Severe and even dangerous side effects, including an increase in heart attacks and sudden death, have occurred with some of these drugs, particularly certain forms, such as short-acting nifedipine. Contrary to previous reports, the drugs do not appear to carry a risk for bleeding ulcers. No one currently taking any calcium channel blocker should stop taking it abruptly, because such action could dangerously increase the risk of high blood pressure.

Anti-Clotting Agents

Anti-clotting agents, either anticoagulants or anti-platelet drugs, are being used to treat unstable angina, to protect against heart attacks, and prevent blood clots during heart surgeries. They may be used alone or in combinations, depending on the severity of the condition. The standard anti-clotting agents are aspirin and heparin. Newer drugs are showing promise, particularly in combination with aspirin and heparin, in relieving angina, in preventing heart attacks, repeat heart surgeries, and death more effectively than aspirin or heparin alone. Many are proving to be more effective even than heparin although more comparative studies are needed to determine the most beneficial approaches. All anti-clotting therapies carry the risk of bleeding, which can lead to dangerous situations, including stroke.

Aspirin. Aspirin inhibits blood platelets (major clotting factors); it is usually the first choice for people with stable angina or those with risk factors for a first heart attack. Aspirin is more effective in reducing pain from unstable than stable angina, but, in both groups, it prevents heart attacks. Prolonged use may produce gastrointestinal ulcers and bleeding.

Heparin. The anticoagulant heparin, used alone or in combination with aspirin, is another standard blood-thinning drug, but it must be intravenously administered and monitored. A 1999 study indicated that adjusting the heparin dose according to the patient's weight when it is administered during acute conditions can reduce the risk for hemorrhage. Enoxaparin (Lovenox) or reviparin are drugs known as low-molecular weight heparin. They require injections but do not need continuous monitoring, as heparin does. Studies are finding that they are very effective for unstable angina; in two studies they outperformed standard heparin. Patients may even be able to self-administer it as people with diabetes do insulin. Studies are finding that it is very effective for unstable angina and for preventing heart attacks. Studies are indicating that it outperforms standard heparin plus aspirin.

Experimental Drugs

Research is showing that the use of antibiotics tetracyclines and quinolones, which are prescribed for Chlamydia pneumoniae and H. pylori, is associated with a lower risk for heart attacks. Fibroblastic growth factor spurs angiogenesis, a process that promotes the growth of tiny blood vessels. In one study, the agent triggered blood vessel growth after bypass surgery in blood-deficient areas of the heart. Ranolazine is a unique drug under investigation that reduces the work of the cells in the heart without damaging them. Early studies are showing success in improving short-term exercise tolerance. In animal studies, retinoic acid, a form of vitamin A, was shown to improve blood vessel function. Nicorandil, know as a potassium channel activator, has anti-ischemic and antiarrhythmic properties and may be a useful add-on for patients who need aggressive treatment. Severe mouth sores have been reported in some patients with long-term use.