Intermittent claudication results from obstruction of blood flow by atheromas in large and medium arteries. Insertion of stents in the obstructed vessels is becoming more common. Supervised exercise therapy is of benefit in reducing claudication and increasing pain-free walking distance. Medical treatment directed at reversal or control of atherosclerosis requires measurement and control of hyperlipidemia (see Chapter 35), hypertension (see Chapter 11), and obesity; cessation of smoking; and control of diabetes, if present. Physical therapy and exercise training are of proven benefit. Conventional vasodilators are of no benefit because vessels distal to the obstructive lesions are usually already dilated at rest. Antiplatelet drugs such as aspirin or clopidogrel (see Chapter 34) are often used to prevent clotting in the region of plaques and have documented benefit in reducing the risk of myocardial infarction, stroke, and vascular death even though they have little or no effect on claudication. Two drugs are used almost exclusively for PAD. Cilostazol, a phosphodiesterase type 3 (PDE3) inhibitor, may have selective antiplatelet and vasodilating effects. This drug has been shown to increase exercise tolerance in patients with severe claudication. Pentoxifylline, a xanthine derivative, is widely promoted for use in this condition but is not recommended. It is thought to act by reducing the viscosity of blood and perhaps increasing the deformability of red blood cells, allowing blood to flow more easily through partially obstructed areas. Naftidrofuryl, a 5-HT2 antagonist, is available outside the USA and appears to have benefits similar to those of cilostazol. Percutaneous angioplasty with stenting may be effective in patients with medically intractable signs and symptoms of lower limb ischemia.
Isosorbide dinitrate: Very similar to nitroglycerin, slightly longer duration of action; no transdermal form
Isosorbide mononitrate: Active metabolite of the dinitrate; used orally for prophylaxis
Oral and parenteral, 4–6 h duration of action • Toxicity: Asthma, atrioventricular block, acute heart failure, sedation • Interactions: Additive with all cardiac depressants
Subclass, Drug Mechanism of Action Effects Clinical Applications Pharmacokinetics, Toxicities, Interactions •PropranololNonselective competitive antagonist at βadrenoceptors Decreased heart rate, cardiac output, and blood pressure•decreasesmyocardial oxygen demand Prophylaxisofangina•forother applications, see Chapters 10, 11, and 13
Atenolol, metoprolol, others: β 1-selective blockers, less risk of bronchospasm, but still significant • Amlodipine, felodipine, other dihydropyridines: Like nifedipine but slower onset and longer duration (up to 12 h or more)
Prophylaxis of angina
Oral, duration 6–8 h • Toxicity: QT interval prolongation (but no increase of torsades de pointes), nausea, constipation, dizziness • Interactions: Inhibitors of CYP3A increase ranolazine concentration and duration of action
Ivabradine: Inhibitor of sinoatrial pacemaker; reduction of heart rate reduces oxygen demand
Trimetazidine, allopurinol, perhexiline, fasudil: See text
Amsterdam EA et al: 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: Executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;130:2354.
Borer JS: Clinical effect of ‘pure’ heart rate slowing with a prototype If inhibitor: Placebo-controlled experience with ivabradine. Adv Cardiol 2006;43:54.