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Coronary artery disease
Description
An in-depth report on the causes, diagnosis, treatment, and prevention of CAD.
Alternative Names
Angina; Atherosclerosis; Heart disease
Other Medications
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. 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 volatile 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 somewhat 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. Some concern exists that nitrate-free periods might increase the risk for angina and adverse heart events. One large study, however, found no increased danger when patients used a nitroglycerine patch with scheduled breaks. The use of high blood pressure drugs known as ACE inhibitors may help prevent tolerance to nitrates.
Side Effects. Nitrates 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, sildenafil (Viagra), and certain antidepressants. 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.
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 are recognized for reducing deaths from heart disease and from heart surgeries, including angiography and coronary bypass. Beta-blockers are the drugs of choice for older patients with stable angina and may also be beneficial for people with silent ischemia. They are, however, less useful for the treatment of Prinzmetal’s angina. Beta-blockers are often prescribed along with other drugs such as nitrates, calcium channel blockers, or statins. A 2006 study suggested that beta-blockers and statins may help stabilize coronary artery disease and prevent the development of heart attacks.
Specific Beta-blockers. 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.
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.)
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 include captopril (Capoten), ramipril (Altace), enalapril (Vasotec), quinapril (Accupril), benazepril (Lotensin), perindopril (Aceon), and lisinopril (Prinivil, Zestril).
Side Effects. Side effects of ACE inhibitors are uncommon but may include an irritating cough, excessive drops in blood pressure, and allergic reactions. In the past, doctors sometimes avoided giving aspirin to patients who were taking ACE inhibitors because the combination was believed to cause kidney problems. But, a 2005 study of patients with both coronary artery disease and heart failure found that taking aspirin and ACE inhibitor together is safe. The researchers also noted that taking aspirin with an ACE inhibitor can significantly reduce the risk of death for older patients with CAD and heart failure.
[For more information on ACE inhibitors, see In-Depth Report #14: High blood pressure.]
Statins and Other Cholesterol and Lipid-Lowering Drugs
In 2004, the National Cholesterol Education Program issued updated recommendations on how to control cholesterol levels. These guidelines emphasize that patients should lower their LDL (“bad”) cholesterol and recommend that more people take LDL-lowering medication. Lowering LDL cholesterol and raising HDL (“good”) cholesterol can significantly reduce the risks of heart disease. Several different types of drugs (statins, bile-acid binding resins, niacin, and fibrates) are used to treat cholesterol. [For more information, see In-Depth Report #23: Cholesterol.]
Statins are among the most important of these drugs. Brands include lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), fluvastatin (Lescol), atorvastatin (Lipitor), and rosuvastatin (Crestor). A major analysis of over 200 studies found that statins reduced the risk for heart problems by 60% and stroke by 17%. A 2005 review found that the more that statins lower LDL, the more they reduce CAD and other heart disease risks.
An important 2006 study found that aggressive treatment with statins may have the potential to reverse coronary artery disease. In the study, rosuvastatin reduced fatty plaque in the arteries in addition to improving LDL and HDL cholesterol levels. Future studies will explore whether other statins have a similar positive effect on coronary artery disease. Rosuvastatin lowers LDL more than most other statins, but may carry a greater risk for more serious side effects.
Side effects of statins may include stomach upset, headaches, skin rashes, muscle aches, sexual dysfunction, drowsiness, dizziness, nausea, constipation, and peripheral neuropathy (numbness or tingling in the hands and feet).
The main safety concern with statins is an uncommon condition called myopathy, which can cause muscle and joint pain and possible muscle damage. Doctors will immediately stop statin therapy if myopathy occurs. Patients should talk to their doctor about any unusual muscle discomfort or weakness, or if their urine becomes brown-colored. Statins can also affect the liver, particularly at higher doses, so patients taking these drugs should receive regular liver function tests.
Infection-Fighting Medications
Influenza Vaccinations (Flu Shots). Evidence now suggests influenza vaccinations help protect against adverse heart events (including after heart surgeries), stroke, and death from all causes in the elderly. Still, studies suggest that only two-thirds of at risk people are vaccinated, mostly because of unwarranted fears of ineffectiveness or adverse effects.
Antibiotics. Researchers have investigated antibiotics for treating patients with heart disease and past infection of the bacteria Chlamydia pneumoniae . Results from several recent large-scale clinical trials suggest that antibiotic treatment provides no benefit in preventing heart attack or other cardiac events in patients with coronary artery disease. In addition, a 2006 study indicated that short-term treatment with the antibiotic clarithromycin may increase the risk for death in patients with coronary artery disease. While it is still possible that C. pneumoniae may play a role in triggering inflammatory responses associated with ACS, antibiotic therapy is no longer considered appropriate for treatment or prevention of heart disease.
Other Drugs
Ranolazine (Ranexa) was approved in 2006 for treatment of chronic angina. It is recommended for patients who have not responded to other angina drugs. Ranolazine is taken in combination with amlodipine, beta blockers, or nitrates. The drug appears to work better in men than in women
Experimental Drugs
Gene Therapy and Angiogenesis. Proteins known as growth factors are being investigated for their ability to grow new blood vessels for supplying oxygen to the heart. After promising small trials, two large studies of genetically engineered forms of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF [GenerX]) failed to detect any benefits. Studies on therapies that actually genetically encode these proteins are underway.
Testosterone Supplements. Some trials using testosterone supplements or patches have reported improved exercise-induced blood flow in the coronary arteries and improvement in angina in some cases. Supplements of this male hormone, however, may increase the risk for prostate cancer. Experts suggest that testosterone be used only in older men with significant deficiencies in testosterone.
Selective Estrogen-Receptor Modulators (SERMs) . Selective estrogen-receptor modulators (SERMs), including raloxifene (Evista), have been designed to produce the benefits of estrogen without its risks. They are thought to act like estrogen in some tissues but behave like estrogen blockers (antiestrogens) in others. Raloxifene may have some heart benefits, although it poses a risk for deep vein blood clots, which may have long-term implications for patients with heart problems. A major study is underway to determine its effects on the heart.
- Review Date: 4/12/2006
- Reviewed By: Harvey Simon, M.D., Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital
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