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Drug Safety 1998-Jul

Choosing the most appropriate treatment for stable angina. Safety considerations.

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The goals of stable angina pectoris treatment are: (i) symptom relief and increase in angina-free walking time; and (ii) reduction of mortality and adverse outcome. Strategies used for plaque stabilisation resulting in a reduction in cardiovascular mortality and morbidity are: smoking cessation; aspirin (acetylsalicylic acid); blood pressure control; lipid lowering agents when low density lipoprotein cholesterol is elevated despite dietary therapy; coronary bypass surgery in patients with left main stem disease or triple vessel coronary disease and diminished left ventricular function; and use of estrogen in postmenopausal women. For symptom relief and to increase angina-free walking time, long acting nitrates, beta-blockers, calcium antagonists and potassium channel openers can be used. Drugs from these 3 classes are all effective when used optimally and choice of initial therapy should consider the presence of concomitant disease and underlying left ventricular function. However, none of the long acting nitrates provide continuous prophylaxis because nitrate tolerance develops during long term therapy. In patients with uncomplicated stable angina, nitrates, beta-blockers and calcium antagonists are all effective. Intermittent nitrate therapy is not associated with tolerance, but headache is a common adverse effect and the patient is unprotected at night and in the early hours of the morning. Concomitant treatment with a beta-blocker may be beneficial if the patient experiences withdrawal or early morning angina. For patients with stable angina and hypertension, therapy with a beta-blocker or a calcium antagonist rather than nitrate is indicated. beta-Blockers are preferred in patients who have had a myocardial infarction, or in those with a history of supraventricular tachyarrhythmias. beta-Blockers may produce excessive slowing of the heart rate, fatigue and bronchospasm in susceptible patients. Calcium antagonists are indicated as initial therapy when beta-blockers are either not tolerated or contraindicated. beta-Blockers and nondihydropyridine calcium antagonists should not be used in patients with sinus bradycardia and those with greater than first degree atrioventricular (AV) block because of the possibility of further slowing of heart rate and/or the development of high grade AV block. When monotherapy with one class is ineffective or associated with adverse effects, the patient should be switched to another class rather than given an additional drug. Optimal monotherapy is often as effective as combination therapy. If maximum monotherapy is only partially effective, a combination therapy which is not additive in terms of adverse effects should be chosen. Triple therapy may be deleterious and no more effective than dual therapy.

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