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Nitrates for unstable angina

Summary

The termunstable angina encompasses heterogeneous clinical syndromes. Fissuring of an atherosclerotic coronary artery plaque with superimposed platelet deposition, with or without additional thrombus formation, is invariably responsible for a prolonged episode of angina at rest, increasing frequency of angina at rest, or with minimal exertion of less than 4 weeks in duration and early postinfarction angina. Plaque progression, rather than plaque fissuring, is the most likely mechanism for progressive reduction in walking distance due to angina in patients who previously have stable angina. Coronary artery spasm is responsible for Prinzmetal's variant angina, but its exact role in other forms of unstable angina is unknown. The mainstay of treatment of unstable angina (prolonged episode of angina at rest and recent onset angina at rest, or with minimal exertion with a crescendo pattern) is aspirin, heparin, or both. Both aspirin and intravenous (IV) heparin or their combination reduce early mortality and the incidence of acute myocardial infarction in patients hospitalized with unstable angina. However, these agents do not promptly relieve chest pain. There are no placebo-controlled studies evaluating the usefulness of nitrates in unstable angina. In open-label studies, continuous therapy with IV nitroglycerin (NTG) for 24 hours or longer has been shown to relieve chest pain in patients with rest angina refractory to therapy with other antianginal agents, including long-acting nitrates. Recurrence of chest pain in patients receiving IV NTG is a common problem and probably represents development of pharmacologic tolerance, but this can be overriden by dose escalation; protracted tolerance during short-term use of IV NTG is usually not a problem. In the acute phase of unstable angina, IV NTG is the preparation of choice as the dose can be rapidly titrated up or down. There is no role of intermittent nitrate therapy in the acute phase of unstable angina. Once the patient is stable for 12–24 hours, IV NTG should be tapered gradually and intermittent therapy with a long-acting nitrate, as outlined for the treatment of stable angina, instituted. Aspirin reduces mortality and morbidity during long-term therapy and should be continued indefinitely. Routine use of morphine and other potent analgesics is not recommended. Patients who do not respond to IV NTG or in whom IV NTG is contraindicated should be treated with a beta-blocker devoid of intrinsic sympathomimetic activity, provided there are no contraindications to beta-blocker therapy. The role of calcium channel blockers in patients nonresponsive to IV NTG is less well defined. In patients already receiving beta-blockers and nitrates, the addition of nifedipine may be beneficial. However, monotherapy with nifedipine or other first-generation dihydropyridines is not recommended. Although there are no large trials of diltiazem or verapamil in unstable angina, these agents are often used in patients who are not candidates for beta-blocker therapy. Patients who are refractory to intensive medical therapy are candidates for coronary angiography and revascularization procedures, provided the coronary anatomy is suitable for such procedures.

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Thadani, U., Opie, L.H. Nitrates for unstable angina. Cardiovasc Drug Ther 8, 719–726 (1994). https://doi.org/10.1007/BF00877118

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Key Words

  • unstable angina
  • nitrates
  • nitrate tolerance
  • nitrate dose escalation to override tolerance