Unstable Angina
Management of acute myocardial infarction with electrocardiographic ST segment elevation dominated clinical research in cardiology in the late 1980’s and early 1990’s following the dramatic results of the GISSI 1 and ISIS-2 2 trials. More recently attention has turned to the Cinderella syndromes of unstable angina and non-Q wave myocardial infarction based on observations that their associated mortality was substantial (mortality from non-Q-wave infarction approaches that of Q-wave infarction), new concepts in the understanding of acute coronary syndromes and on advances in therapy 3.
Unstable angina is a clinical syndrome diagnosed by a history of new-onset angina, more frequent angina, more persistent angina or rest angina. Braunwald has recently proposed subdividing unstable angina into 5 separate syndromes, each with a different basis and approach to management 4. These are (i) nonocclusive thrombus on a pre-existing atheromatous plaque, which has usually undergone disruption; (ii) dynamic obstruction, i.e. various forms of coronary spasm; (iii) progressive mechanical obstruction, due to progression of atherosclerotic lesions or the development of restenotic lesions after angioplasty; [(iv) inflammation and/or infection of an atheromatous plaque, as yet unproved] and (v) secondary to systemic diseases that impair oxygen delivery (e.g. anemia) or increase heart work (e.g. thyrotoxicosis).
The management of unstable angina (other than new-onset angina and gradually progressive angina) has conventionally been based on hospital admission, rest, analgesia, observation for complications, antithrombotic therapy with heparin, antiplatelet therapy with aspirin and oral antianginal therapy, particularly with nitrates and b-blockers.
A series of recent clinical trials have suggested additional clinical benefit from administration of platelet glycoprotein IIb/IIIa receptor antagonists. The PRISM trial showed a significant risk reduction in the rate of death, MI, or refractory ischemia (3.8 % vs. 5.6 %) during a 48-hour infusion of tirofiban alone compared with heparin alone 5. Eptifibatide with heparin, evaluated in the PURSUIT Trial 6, reduced the risk of death and MI at 30 days from 15.7% to 14.2% when compared with heparin alone. Low molecular weight heparins are safe, at least as effective as unfractionated heparin (UFH) 7, more convenient to administer and require no laboratory monitoring and in the ESSENCE study the rate of death, MI or recurrent angina at 30 days was significantly lower following treatment with enoxaparin compared with UFH (19.8% vs. 23.3%) 8. Trials that have compared bypass surgery with medical therapy or angioplasty with medical therapy have not shown benefit with a routine early aggressive strategy (for review see ref. 3). However such procedures are indicated in patients with persistent ischemia (spontaneous or inducible) despite medical therapy. When angioplasty is undertaken in the setting of unstable angina, adjuvant glycoprotein IIb/IIIa antagonist therapy should be used 9-11.
Within the framework proposed by Braunwald 4, tailored therapy will benefit different patient subtypes. Those with predominantly vasospasm will merit nitrates and calcium channel blockers; those with progressive luminal stenosis merit early revascularization and those with mostly thrombus should improve with aggressive antiplatelet and antithrombotic regimes. Future advances may include anti-inflammatory therapy and oral glycoprotein IIb/IIIa antagonists.
The latest clinical guidelines in the treatment of ACS are here in Acrobat format.
References
1. Long-term effects of intravenous thrombolysis in acute myocardial infarction: final report of the GISSI study. Gruppo Italiano per lo Studio della Streptochianasi nell'Infarto Miocardico (GISSI). Lancet 1987;2: 871-42. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988; 2: 349-603. Theroux P, Fuster V. Unstable Angina and Non–Q-Wave Myocardial Infarction. Circulation. 1998; 97: 1195-2064. Braunwald E. Unstable angina. An etiologic approach to management. Circulation 1998; 98: 2219-225. Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) Study Investigators. A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina. N Engl J Med 1998; 338: 1498-5056. The PURSUIT Trial Investigators. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. N Engl J Med 1998; 339: 436-43 7. Klein W, Buchwald A, Hillis SE et al. Comparison of low-molecular-weight heparin with unfractionated heparin acutely and with placebo for 6 weeks in the management of unstable coronary artery disease. Circulation 1997; 96: 61–88. Cohen M, Demers C, Gurfinkel E et al. Low molecular weight heparin versus unfractionated heparin for unstable angina and non-Q wave myocardial infarction. N Engl J Med 1997; 337: 447–529. The EPIC Investigators. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. N Engl J Med 1994; 330: 956-6110. The CAPTURE Investigators. Randomised placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE Study. Lancet 1997; 349: 1429-3511. The EPISTENT Investigators. Randomised placebo-controlled and balloon-angioplasty-controlled trial to assess safety of coronary stenting with use of platelet glycoprotein-IIb/IIIa blockade. Lancet 1998; 352: 87-92
Niall Herity, M.D.