Unstable Angina Treatments ========================== þ ASA 160 mg daily -- Class A - 50% decrease in mortality, compared to 23% in MI as per ISIS-2 [Cairns J, Theroux P, Armstrong P, et al. Unstable angina: Report from a Canadian roundtable. Can J Cardiol 1996;100:139-154.] [Lewis HD, Davis JW, Archibald DG, et al. Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. Results of a Veterans Administration cooperative study. N Engl J Med 1983;309:396-403.] [RISC Group. Risk of myocardial infarction and death during treatment with low dose aspirin and IV heparin in men with unstable coronary artery disease. Lancet 1990;336:827-30.] þ other antiplatelet drugs: - ticlodipine, clopidogrel, abciximab, integrelin, lamifibam; currently in trials, look very promising. þ Low Molecular Weight Heparin (LMWH) - FRISC study, reported March 1997, Circulation: ASA vs. LMWH, LMWH better [FRISC Group. Low molecular weight heparin during instability in coronary artery disease. Lancet 1996;347:561-68.] - FRIC study, reported July 1997, Circulation: Heparin vs. LMWH: no difference, trend favored regular heparin being better. (All got ASA, too) - ESSENCE, NEJM Aug 1997: Heparin vs. Enoxaparin: Number Needed to Treat (NNT) about 30 for Enoxaparin over Heparin, no increase in major bleeds. (All got ASA too.) - TIMI 11B: LMWH superior Antman EM, McCabe CH, Gurfinkel EP, et al. Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction. Results of the thrombolysis in myocardial infarction (TIMI) 11B trial [see comments]. Circulation 1999; 100 1593-601.] Abstract: - A meta-analysis of ESSENCE and TIMI 11B concludes it's superior to unfractionated heparin [Antman EM, Cohen M, Radley D, et al. Assessment of the treatment effect of enoxaparin for unstable angina/non-Q-wave myocardial infarction. TIMI 11B-ESSENCE meta-analysis [see comments] Circulation 1999; 100 1602-8.] Abstract: - Enoxaparin seems to be the LMWH of choice: Cohen M. Low molecular weight heparins in the management of unstable angina/non- Q-wave myocardial infarction. Semin Thromb Hemost 1999; 25 113-21.] Abstract: þ "Regular" Heparin -- Class B - Heparin added to aspirin may have some effect; most studies are small: [De Bono DP et al. Effect of early IV heparin on coronary patency, infarct size, and bleeding complications after alteplase thrombolysis: results of a ransomised doiuble blind European Cooperative Study Group trial. British Heart J 1992;67:122.] [Theroux P, et al. Aspirin, heparin or both to treat unstable angina. N Engl J Med 1988;319:1105-11.] [RISC Group. Risk of myocardial infaction and death during treatment with low dose aspirin and intravenous heparin with unstable coronary artery disease. Lancet 1990;336:827-830.] - one meta-analysis concludes it's worthwhile: [Oler A, Whooley MA, Oler J, et al. Adding heparin to aspirin reduces the incidence of myocardial infarction and death in patients with unstable angina. A meta-analysis. JAMA 1996;276:811=815.] þ hirudin (new generic name: desirudin): experimental, in Gusto IIb - easier to regulate than heparin - for death/MI at 30 days, no significant difference with heparin - slight trend toward significance early - will be evaluated more in OASIS trial. þ Beta Blockers - Atenolol or metoprolol 5 mg IV Q5' x 3 as needed to get HR of 50-60, or - (for borderline-suitable patients) esmolol 5 mg/100cc at 50-200 micrograms/kg/min. (70 kg = 40cc/hr = 100 micrograms/kg/min) - contraindicated if: + decompensated CHF + respiratory failure + second-degree or worse heart block + SBP less than 90 þ Calcium Channel Blockers - Nifedipine is bad, at least if not in conjunction with beta blockers. [HINT Group. Early treatment of unstable angina in the coronary care unit: A randomized, double-blind, placebo controlled comparsion of recurrent ischemia in patients treated with nifedipine or metoprolol or both. Br Heart J 1986;56:400-13.] [MullerJE, Turi ZG, Pearle DL, et al. Nifedipine and conventional therapy for unstable angina pectoris: a randomized, double-blind comparison. Circulation 1984;69:728-739.] þ Nitroglycerine Bolus: - "It's great to see so many people using iv nitroglycerin boluses! We described our experience with bolus IV nitroglycerin (IV NTG) for chest pain a couple of years ago. (Nashed AH, Allegra JR, Larsen S, Horowitz M. Bolus IV Nitroglycerin Treatment of Ischemic Chest Pain in the ED. Am J Emerg Med 1994;12:288). We use boluses of IV NTG 50mg in 250cc D5W, and give it over 1 to 2 minutes. Doses depend on the systolic blood pressure. We give 0.4mg (1/150 dose) at 60cc/hr iv over 2 minutes for someone with a SBP of 180 or greater, 0.3 (60 cc/hr for 1/5 min.) if the SBP is between 140 and 180. Our dose is 0.15mg for SBP of 110 to 140. The dose is repeated every 5 minutes and depends on the immediate pre-bolus SBP. We have seen very little significant hypotension as a result. One caveat: our patients have usually already received sublingual nitrates as well without significant hypotensive episodes." --Ash Nashed, MD, FACEP Assistant Director Residency in Emergency Medicine Morristown Memorial Hospital - "I've been teaching (preaching?) bolus nitroglycerin for quite a while, and you're right, the bolus is 3-500ucg, but should be given over about five minutes. THis approximates what we're doing with sublingual. Thus, for regular dose nitro (100mg /250 cc). THis is 15 cc/min (100ucg/min) for 3 to 5 minutes. I have used even higher doses for Acute Pulmonary edema (like 300 ucg/min) for brief periods (minutes or until BP starts to drop). The major precaution is with patients who have aortic stenosis and who are sensitive to drops in preload." -- Richard Hamilton MD Clinical Director, Emergency Center Allegheny Hospitals - MCP Program Director, Medical Toxicology Fellowship Department of Emergency Medicine