Literature Review
Table of Contents
Etiology and Pathogenesis of STEMI/UA/NSTEMI
Braunwald E. Unstable angina: an etiologic approach to management. Circulation 1998;98:2219-22 PMID: 9826306
Braunwald E, Mark DB, Jones RH, et al. Unstable Angina: Diagnosis and Management. 1994;AHCPR Publication No. 94-0602;1-154
DeWood MA, Stifter WF, Simpson CS, et al. Coronary angiographic findings soon after non-Q-wave myocardial infarction. N Engl J Med 1986;315:417-23 PMID: 3736619
Theroux P, Fuster V. Acute coronary syndromes: unstable angina and non-Q-wave myocardial infarction. Circulation 1998;97:1195-206 PMID: 9537346
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Risk Stratification
Diagnostic mishaps in the ER
Roger VL, Killian JM, Weston SA, et al. Redefinition of myocardial infarction: prospective evaluation in the community. Circulation 2006;114:790-7. PMID: 16908764
Galvani M, Ottani F, Ferrini D, et al. Prognositic influence of elevated values of cardiac troponin I in acute chest pain by means of rapid testing for cardiac troponin T or troponin I. N Engl J Med 1997;337:1648-53. PMID: 9133515
McCarthy BD, Beshansky JR, D'Agostino RB, Selker HP. Missed diagnoses of acute myocardial infarction in the emergency department: results from a multicenter study Ann Emerg Med. 1993;22:579-82. PMID: 8442548
Pope JH, Aufderheide TP, Ruthazer R, Woolard RH, Feldman JA, Beshansky JR, et al. Missed diagnoses of acute cardiac ischemia in the emergency department N Engl J Med. 2000;342:1163-70. PMID: 10770981
Lee TH, Rouan GW, Weisberg MC, Brand DA, Acampora D, Stasiulewicz C, et al. Clinical characteristics and natural history of patients with acute myocardial infarction sent home from the emergency room Am J Cardiol. 1987;60:219-24. PMID: 3618483
Hamm CW, Goldmann BU, Heeschen C, Kreymann G, Berger J, Meinertz T. Emergency room triage of patients with acute chest pain by means of rapid testing for cardiac troponin T or troponin. N Engl J Med 1997;337:1648-53. PMID: 9385123
Galvani M, Ottani F, Ferrini D, et al. Prognostic influence of elevated values of cardiac troponin I in patients with unstable angina. Circulation 1997;95:2053-9. PMID: 9133515
Cardiac Biomarkers
Christenson RH, Vaidya H, Landt Y, et al. Standardization of creatinine kinase-MB CK-MB) mass assays: the use of recombinant CK-MB as a reference material. Clin Chem 1999;45:1414-23. PMID: 10471643
Jaffe AS, Babuin L, Apple FS. Biomarkers in acute cardiac disease: the present and the future. J Am Coll Cardiol 2006;48:1-11. PMID: 16814641
Braumwald E, Antman EM, Beasley JW et al ACC/ AHA guidelines for management of Patients with Unstable angina on non-ST- Segment elevation MI, a Report for the Am Coll of Cardiol/ Am Heart Association Task Force on Practice Guidelines J Am Coll Cardiol 2000;36:970 -1062. PMID: 10987629
Until approximately nine years ago, CPK-MB was the best cardiac marker available. In retrospect they were not as sensitive as believed. It is estimated that one third of patients presenting without an ST-elevation and without elevations in the CPK-MB who were mistakenly diagnosed with unstable angina are now being recognized as having a Non-ST elevation MI based on positive troponin levels.
Henrikson, CA, Howell EE, Bush DE, et al. Prognostic Usefulness of Marginal Troponin T Elevation. Am J Cardiol 93:275-79. PMID: 14759374
Essentially, a Troponin is “positive” anytime it is not completely negative. Even very small elevations of troponin correlate with the worse clinical outcomes in the ACS patient.
Clark, M, Payne, J. Elevated Cardiac Troponins: Their Significance in Actue Coronary Syndrome and Noncardiac Conditions. J Okla St Med Assoc. 2006;99:6
PMID: 16821493
Troponin T binds to tropomysin, remains elevated for 8-21 days and is less specific than Troponin I. Trononin I binds to actin, is more specific in renal failure and remains elevated for 5-10 days. Most institutions now use TnI.
Giugliano, R, Braunwald, E The Year in Non-ST-Segment Elevation Acute Coronary Syndromes J Am Coll Cardiol 2005;46:906-919 PMID: 17903640
The absolute value of the troponin correlates with the intracoronary thrombus identified angiographically.
Achar, S, Kundu S., Norcross W. Diagnosis of Acute Coronary Syndrome. Am Fam Physic. 2005;72:119-26. PMID: 16035692
Changes in myoglobin concentration can be useful where the presence of myocardial injury is already established and there’s a concern reinfarction may have occurred. The plasma myoglobin will rise within an hour and fall precipitously in the next 3-4 hours, indicating a new myocyte injury.
ECG findings
Brush JE Jr, Brand DA, Acampora D, Chalmer B, Wackers FJ. Use of the initial electrocardiogram to predict in-hospital complications of acute myocardial infarction. N Engl J Med 1985;312:1137-41. PMID: 4022062
Fesmire FM, Percy RF, Wears RL, MacMath TL. Risk stratification according to the initial electrocardiogram in patients with suspected acute myocardial infarction. Arch Inern Med 1989;849:1294-7. PMID: 2730248
Fesmire FM, Percy RF, Wears RL. Diagnostic and prognostic importance of comparing the initial to the previous electrocardiogram in patients admitted for suspected acute myocardial infarction. South Med J 1991;84:841-63. PMID: 2068623
de Zwaan C, Bar FW, Janssen JH, et al. Angiographic and clinical characteristics of patients with unstable angina showing an ECG pattern indicating critical narrowing of the proximal LAD coronary artery. Am Heart J 1989;117:657-65. PMID: 2784024
Marked T wave inversions (2 mm or greater) in anterior precordial leads strongly suggests acute ischemia, particularly that due to a critical stenosis of the LAD.
Renkin J, Wijns W, Ladha Z, Col J. Reversal of segmental hypokinesis by coronary angioplasty in patients with unstable angina, persistent T wave inversion, and left anterior descending coronary artery stenosis. Additional evidence for myocardial stunning in humans.Circulation1990;82:913-21. PMID: 2394011
Patients with T inversions in anterior precordial leads T inversions and hypokinesis of the anterior wall are at high risk if given medical treatment alone.
Zalenski RJ, Rydman RJ, Sloan EP, et al. ST segment elevation and the prediction of hospital life-threatening complications: the role of right ventricular and posterior leads. J Electrocardiol 1998;3 Suppl:164-71. PMID: 9988023
Approximately 4% of acute MI patients will demonstrate an ST-segment elevation isolated to the posterior chest leads V7 thru V9. The presence of ST-segment elevation in right ventricular leads (V4R thru V6R) or posterior leads (V7 thru V9) adds additional prognostic information to a patient presenting with inferior ST-segment elevation.
Matetzky S, Freimark D, Chouraqui P, et al. Significance of ST segment elevations in posterior chest leads (V7 to V9) in patients with acute inferior myocardial infarction: application for thrombolytic therapy. J Am Coll Cardiol 1998;31:506-11. PMID: 9502627
ST-segment elevation in V7 thro V9 is diagnostically important since it qualifies the patient for consideration of acute reperfusion therapy.
Lee, TH, Rouan GW, Weisberg, MC, et al. Sensitivity of routine clinical criteria for diagnosing myocardial infarction within 24 hours of hospitalization. Ann Intern Med 1987; 106:181-6 PMID: 3800180
Lee, TH, Juarez GJ, Cook EF, Weisberg MC, Rouan GW, Brand DA, Goldman L. Ruling out Acute Myocardial Infarction A prospective Multicenter Validation of a 12-hour Strategy for Patients at Low Risk. N Engl J Med. 1991;324:1239-46. PMID: 2014037
TIMI Risk Score
Antman EM, Cohen M, Bernink PJ, McCabe CH, Horacek T, Papuchis G, et al. The TIMI risk score for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making. JAMA 2000;284:835-42. PMID: 10938172
Mulitple clinical factors other than the results of cardiac biomarkers should be included in determining whether a patient will undergo a revascularization.
Actual tool is in:
Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina//non-ST segment elevation MI. Circulation 2007;116:903-877 PMID: 17679616
GRACE Prediction Score
Eagle KA, Lim MJ, Dabbous OH, et al. A validated prediction model for all forms of acute coronary syndrome: estimating the risk of 6-month postdischarge death in an international registry. JAMA 2004;291:2727-33. (GRACE Prediction Model) PMID: 15187054
Granger CB, Goldberg RJ, Dabbous O, et al. Predictors of hospital mortality in the global registry of acute coronary events. Arch Intern Med 2003;163:2345-53. PMID: 14581255
PURSUIT Risk Model
Boersma E, Pieper KS, Stayerberg EW, et al. Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation. Results from an international trial of 9461 patients. The Pursuit Investigators. Circulation 2000;101:2557-67. PMID: 10840005
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Early Invasive vs Early Conservative Management of UA/NSTEMI
Effects of tissue plasminogen activator and a comparison of early invasive and conservative strategies in unstable angina and non-Q myocardial infarction: results of the TIMI IIIB trial. TIMI IIIB Trial Investigators. Circulation 89:1545, 1994. PMID: 8149520
The study showed the initial hospitalization was longer and the need for rehospitalization more frequent in the group receiving conservative treatment.
Boden WE, O’Rourke RA, Crawford MH, et al: Outcomes in patients assigned with acute non-Q-wave myocardial infarction randomly assigned to an invasive as compared with a conservative management strategy. Veterans Affairs Non-Q Wave Infarction Strategies. N Engl J Med 338:1785, 1998. PMID: 9632444
McCullough PA, O’Neill WW, Graham M, et al: A prospective randomized trial of triage angiography in acute coronary syndromes ineligible for thrombylysis therapy: results of Medicine versus Angiography in Thrombolyitic exclusion (MATE). J Am Coll Card 32:596, 1998 PMID: 9741499
Invasive compared with non-invasive treatment in unstable coronary artery disease: FRISC II prospective randomized multicenter study. Fragmin and Fast Revascularization during Instability in Coronary Artery Disease Investigators. Lancet 354:708, 1999. PMID: 10475181
An early invasive strategy was shown to reduce both mortality and myocardial infarction at one year.
Morrow DA, Cannon CP, Rifai N, et al, for the TACTICS – TIMI 18 Investigators. Ability of minor elevations of troponins I and T to predict benefit from an early invasive strategy in patients with unstable angina and non-ST elevation myocardial infarction. Results from an randomized trial. JAMA. 2001. Nov 21;286:2405-12. PMID: 11712935
Patients at the greatest risk, such as those with positive troponin values and with ST segement depression at the study level, had the highest event rate and derived the greatest benefit from an invasive strategy.
Holmvang L, Clemmensen P, Lindahl B, et al: Quantitative analysis of the admission electrocardiogram identifies patients with unstable coronary artery disease who benefit the most from early invasive treatment. J Am Coll Card 41:905, 2003. 12651033
Choudhry NK, Singh JM, Barolet A, Tomlinson GA, Detsky AS. How should patients with unstable angina and non-ST-segment elevation myocardial infarction be managed: A meta-analysis of randomized trials. Am J Med. 2005;118:465-74. PMID: 15866246
Mehta SR, Cannon CP, Fox KA, et al. Routine vs selective invasive strategies in patients with acute coronary syndromes: a collaborative meta-analysis of randomized trials. JAMA. 2005;293:2908-17. PMID: 15956636
Spacek R, Widimsky P, Straka Z, et al. Value of first day angiography/angioplasty in evolving non-ST segment elevation myocardial infarction: an open multicenter randomized trial. The Vino Study. Eur Heart J 2002;23:230-8. PMID: 11792138
deWinter RJ, Windhausen F, Cornel JH, et al. Early invasive versus selectively invasive management for acute coronary syndromes. N Engl J Med 2005;353:1095-104. PMID: 16162880
Fox KA, Poole-Wilson P, Clayton TC, et al. 5-year outcome of an interventional strategy in non-ST-elevation acute coronary syndrome: the British Heart Foundation RITA 3 randomized trial. Lancet 2005;366:914-20. PMID: 16154018
Widimsky P, Groch L, Zelizko M, et al. Eur Heart J. 2000;21:823-31. PRAGUE Trial. PMID: 10781354
The PRAGUE trial supports transfer of STEMI patient for PCI without administering thrombolytics beforehand if PCI will be available in less than 90 minutes.
Cannon CP, Gibson CM, McCabe CH, et al. Circulation 1998;98:2805-14. PMID: 9860780
Although thrombolysis reduces mortality more than placebo, normal blood flow is restored in only 60% of patients.
Gershlick AH, Stephens-Lloyd A, Hughes S, et al. Rescue angioplasty after failed thrombolytic therapy for acute myocardial infarction. N Engl J Med. 2005;353:2758-68. REACT Trial PMID: 16382062
Treatment of STEMI with PCI is well-established. However, due to limited resources in some facilities for PCI, first-line therapy in 30-70% of patients is thrombolytic therapy. The REACT trial shows the superiority of rescue PCI over conservative treatment or repeated thrombolysis in patients without clinical reperfusion at 90 minutes after initial thrombolysis.
For STEMI patients who undergo thrombolytic therapy, immediate transfer to a PCI center should be facilitated so there’s no delay in undergoing angiography if thrombolytic reperfusion is incomplete.
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Medications
Anti-platelet agents
Aspirin
Antiplatelet Trialists’ Collaboration. Collaborative overview of randomized trials of antiplatelet therapy—I: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy invarious categories of patients. BMJ 1994;308:81–106. PMID: 8298418
Antithrombotics Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002; 324:71– 86. PMID: 11786451
Lewis HDJ, 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. PMID: 6135989
Théroux P, Ouimet H, McCans J, et al. Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med 1988;319:1105–11. PMID: 3050522
Eikelboom JW, Quinlan DJ, Mehta SR, et al. Unfractionated and low-molecular-weight heparin as adjuncts to thrombolysis in aspirin-treated patients with ST-elevation acute myocardial infarction: a meta-analysis of the randomized trials. Circulation. 2005;112:3855-67. PMID: 16344381
Enoxaparin is superior to UFH in reducing reinfarction and death but increased minor and major bleeding
Thienopyridines
CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996;348:1329 –39. PMID: 8918275
Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001;345:494 –502. PMID: 11519503
Mehta SR, Yusuf S, Peters RJ, et al. Effects of pretreatment with clopidogrel and aspirin followed by long- term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 2001;358:527–33. PMID: 11520521
Anticoagulants
Heparin
Theroux P, Waters D, Qiu S, McCans J, de Guise P, Juneau M. Aspirin versus heparin to prevent myocardial infarction during the acute phase of unstable angina. Circulation 1993;88:2045– 8. PMID: 8222097
Holdright D, Patel D, Cunningham D, et al. Comparison of the effect of heparin and aspirin versus aspirin alone on transient myocardial ischemia and in-hospital prognosis in patients with unstable angina. J Am Coll Cardiol 1994;24:39–45. PMID: 8006281
Oler A, Whooley MA, Oler J, Grady D. Adding heparin to aspirin reduces the incidence of myocardial infarction and death in patients with unstable angina. A meta-analysis. JAMA 1996;276:811–5. PMID: 8769591
Cohen M, Adams PC, Parry G, et al. Combination antithrombotic therapy in unstable rest angina and non-Q-wave infarction in nonprior aspirin users: primary end points analysis from the ATACS trial. Antithrombotic Therapy in Acute Coronary Syndromes Research Group. Circulation 1994;89:81– 8. PMID: 8281698
LMWH
Cohen M, Demers C, Gurfinkel EP, et al. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. N Engl J Med 1997;337:447–52. PMID: 9250846
Antman EM, McCabe CH, Gurfinkel EP, et al. Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Qwave myocardial infarction: results of the Thrombolysis In Myocardial Infarction (TIMI) 11B trial. Circulation 1999;100:1593– 601. PMID: 10517729
Ferguson JJ, Califf RM, Antman EM, et al. Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial. JAMA 2004;292:45–54. PMID: 15238590
Collet JP, Montalescot G, Lison L, et al. Percutaneous coronary intervention after subcutaneous enoxaparin pretreatment in patients with unstable angina pectoris. Circulation 2001;103:658–63. PMID: 11156876
Study reporting ability to use LMWH even in setting of PCI
Bivalrudin
Ferguson JJ, Califf RM, Antman EM, et al. Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial. JAMA 2004;292:45–54. PMID: 15238590
Stone GW, McLaurin BT, Cox DA, et al. Bivalirudin for patients with acute coronary syndromes. N Engl J Med 2006;355:2203–16. PMID: 17124018
Fondaparinux
Yusuf S, Mehta SR, Chrolavicius S, et al. Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N Engl J Med 2006;354:1464 –76. PMID: 16537663
Yusuf S, Mehta SR, Chrolavicius S, et al. Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial. JAMA 2006;295:1519 –30. PMID: 16537725
Platelet GP IIb/IIIa Receptor Antagonists
Boersma E, Harrington RA, Moliterno DJ, et al. Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta analysis of all major randomized clinical trials. Lancet 2002;359:189–98. PMID: 11812552
GP IIb/IIIa inhibitors are of substantial benefit in patients with UA/NSTEMI who undergo PCI, of modest benefit in patients who are not routinely scheduled to undergo revascularizaition (but may do so) and are of questionable benefit in patients who do not undergo revascularization.
Coller BS. Potential non-glycoprotein IIb/IIIa effects of abciximab. Am Heart J. 1999;138:S1-S5.
Platelet aggregation gradually returns to normal 24-48 hours after discontinuation of the drug.
PMID: 10385784
Simoons ML, Effect of glycoprotein IIb/IIIa receptor blockade abciximab on outcome in patients with acute coronary syndromes without early coronary revascularization: the GUSTO IV-ACS randomized trial. Lancet 2001;357:1915-24. PMID: 11425411
GUSTO IV-ACS enrolled patients in whom early (less than 48 hours) revascularization was not intended. Results suggest that abciximab in the dose regimens used in GUSTO IV-ACS is not indicated in the management of patients with UA or NSTEMI when early invasive management is not intended.
The EPIC Investigation. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. N Engl J Med 1994;330:956–61 PMID: 8121459
The EPILOG Investigators. Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. N Engl J Med 1997;336:1689 –96 PMID: 9182212
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. Evaluation of Platelet IIb/IIIa Inhibitor for Stenting. Lancet 1998;352:87–92 PMID: 9672272
Abciximab
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 –35. PMID: 9164316
The EPIC Investigation. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. N Engl J Med 1994;330:956–61. PMID: 8121459
The EPILOG Investigators. Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. N Engl J Med 1997;336:1689 –96. PMID: 9182212
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. Evaluation of Platelet IIb/IIIa Inhibitor for Stenting. Lancet 1998;352:87–92. PMID: 9672272
Simoons ML. Effect of glycoprotein IIb/IIIa receptor blocker abciximab on outcome in patients with acute coronary syndromes without early coronary revascularisation: the GUSTO IV-ACS randomized trial. Lancet 2001;357:1915–24. PMID: 11425411
Evidence that Abciximab should not be used unless PCI is planned
Kastrati A, Mehilli J, Neumann FJ, et al. Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial JAMA. 2006;295:1531-8. PMID: 16533938
Abciximab showed clinical benefit over placebo following clopidogrel therapy by reducing the composite endpoint of death, MI or urgent revascularization. GP IIa/IIIb treatment effect was enhanced and statistically significant only in the higher-risk, troponin-positive patients. The results also corroborate previous analysis that showed GP IIb/IIIa inhibitors were not required in troponin-negative patients with ACS or low-risk patients having elective PCI who were pretreated with clopidogrel.
Tirofiban
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 –505. PMID: 9599104
Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) Study Investigators. Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction. N Engl J Med 1998;338:1488 –97. PMID: 9599103
The RESTORE Investigators. Effects of platelet glycoprotein IIb/IIIa blockade with tirofiban on adverse cardiac events in patients with unstable angina or acute myocardial infarction undergoing coronary angioplasty. Randomized Efficacy Study of Tirofiban for Outcomes and REstenosis. Circulation 1997;96:1445–53. PMID: 9315530
Eptifibatide
The PURSUIT Trial Investigators. Inhibition of platelet glycoproteinIIb/IIIa with eptifibatide in patients with acute coronary syndromes. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy. N Engl J Med 1998; 339:436–43. PMID: 9705684
Phillips DR, Scarborough RM. Clinical pharmacology of eptifibatide. Am J Cardiol 1997;80:11B-20B. PMID: 9291241
Eptifibatide has a half-life of 2-3 hours. Platelet aggregation returns to normal 4- hours after discontinuation of the drug.
Beta-Blockers
Ellis K, Tcheng JE, Sapp S, Topol EJ, Lincoff AM. Mortality benefit of beta blockade in patients with acute coronary syndromes undergoing coronary intervention: pooled results from the Epic, Epilog, Epistent, Capture and Rapport trials. J Interv Cardiol 2003;16:299–305. PMID: 14562669
Chen ZM, Pan HC, Chen YP, et al. Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 2005;366:1622–32. PMID: 16271643
Raised question of worse outcomes with early IV Beta Blocker usage
Ace Inhibitors
ACE Inhibitor Myocardial Infarction Collaborative Group. Indications for ACE inhibitors in the early treatment of acute myocardial infarction: sytemic overview of individual data from 100,000 patients in randomized trials. Circulation 1998;97:2202-12. PMID: 9631869
ACE Inhibitors reduce mortality rates in patients with MI or who recently had an MI and have LV dysfuncition.
Buch P, Rasmussen S, Abildstrom SZ, Kober L, Carlsen J, TorpPedersen C. The long term impact of the angiotensin converting enzyme inhibitor trandolapril on mortality and hospital admissions in patients with left ventricular dysfunction after a myocardial infarction: follow-up to 12 years. Eur Heart J 2005;26:145-52. PMID: 15618070
Follow-up of patients with LV dysfunction after MI in the TRACE trial regarding mortality and hospitalization rate was maintained for upwards of 10-12 years.
ARBs
Pfeffer MA, McMurray JJ, Velazquez EJ, et al. Valsartan, captopril or both in myocardial infarction complicated by heart failure, left ventricular dysfunction or both. N Engl J Med 2003;360:1037-433. PMID: 14610160
The ARB valsartan was as effective as captorpil in patients at high risk for cardiovascular events after MI. However, the combination of valsartan and captopril increased adverse events and did not improve survival.
Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003;348:1309-21. PMID: 12668699
Eplerenone given to MI patients with either heart failure or diabetes mellitus had a reduced morbidity and mortality in the EPHESUS study.
Statins
Schwartz GG, Olsson AG, Ezekowitz MD, et al. Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA. 2001 Apr 4;285(13):1711-8. PMID: 11277825
Briel M, Schwartz GG, Thompson PL, et al. Effects of Early Treatment With Statins on Short-term Clinical Outcomes in Acute Coronary Syndromes: A Meta-analysis of Randomized Controlled Trials. JAMA. 2006;295:2046-2056. PMID: 16670413
Fonarow GC, Wright RS, Spencer FA, et al. Effect of statin use within the first 24 hours of admission for acute myocardial infarction on early morbidity and mortality. Am J Cardiol. 2005;96:611-616. PMID: 16125480
Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350:1495-1504. PMID: 15007110
Calcium Channel Blockers
Held PH, Yusuf S, Furberg CD. Calcium channel blockers in acute myocardial infarction and unstable angina: an overview. BMJ 1989; 299:1187–92. PMID: 2513047
Gibson RS, Boden WE, Theroux P, et al. Diltiazem and reinfarction in patients with non-Q-wave myocardial infarction. Results of a double-blind, randomized, multicenter trial. N Engl J Med 1986; 315:423–9. PMID: 3526151
Nitrates
Yusuf S, Collins R, MacMahon S, Peto R. Effect of intravenous nitrates on mortality in acute myocardial infarction: an overview of the randomised trials. Lancet 1988;1:1088 –92. PMID: 2896919
Morphine
Meine TJ, Roe MT, Chen AY, et al. Association of intravenous morphine use and outcomes in acute coronary syndromes: results from the CRUSADE Quality Improvement Initiative. Am Heart J 2005;149:1043–9. PMID: 15976786
Prompted downgrading of morphine usage from Class 1 to 2a
Clopidogrel
Sabatine MS, Cannon CP, Gibson CM, et al. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med. 2005;352:1179-89. PMID: 15758000
Combining aspirin with clopidogrel shows significant benefit in patients with acute coronary syndromes and those undergoing percutaneous revascularization.
Bhatt DL, Fox KA, Hacke W, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothromboitc events. N Engl J Med. 2006;354:1706-17. PMID: 16531616
The Charisma trial took 15,603 patients with multiple atherothrombotic risk factors and placed in aspirin alone vs clopidogrel plus aspirin group. Groups did not differ for all-cause mortality, CV death or nonfatal MI.
Plavix
Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. NEJM. 2007 Nov 15;357(20):2001-15. PMID: 17982182
Eriksson P. Long-term clopidogrel therapy after percutaneous coronary intervention in PCI-CURE and CREDO: the "Emperor's New Clothes" revisited. Eur. Heart J. 2004;25:720–722. PMID: 15120880
Fox, KA, Mehta, SR, Peters, R, et al. Benefits and risks of the combination of clopidogrel and aspirin in patients undergoing surgical revascularization for non-ST-elevation acute coronary syndrome: the Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (CURE) Trial. Circulation 2004; 110:1202. PMID: 15313956
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Procedures
Electrocardiogram at presentation
Bayes de Luna A, Wagner G, Birnbaum Y, et al. A new terminology for left ventricular walls and location of myocardial infarcts that present Q wave based on the standard of cardiac magnetic resonance imaging: a statement for healthcare professionals from a committee appointed by the International Society for Holter and Noninvasive Electrocardiography. Circulation 2006;114:1755-60. PMID: 17043179
Rouan GW, Lee TH, Cook EF, Brand DA, Weisberg MC, Goldman L. Clinical characteristics and outcome of acute myocardial infarction in patients with initially normal or nonspecific electrocardiograms (a report from the Multicenter Chest Pain Study). Am J Cardiol 1989;64:1087-92. PMID: 2683709
Savonitto S, Ardissino D, Granger CB, et al. Prognostic value of the admission electrocardiogram in acute coronary syndromes. JAMA 1999;281:707-13. PMID: 10052440
Selker HP, Zalenski RJ, Antman EM, et al. An evaluation of technologies for identifying acute cardiac ischemia in the emergency department: a report from a National Heart Attack Alert Program Working Group. Ann Emerg Med 1997;29:13-87. PMID: 8998086
History and physical examination
Morise AP, Haddad WJ, Beckner D. Development and validation of a clinical score to estimate the probability of coronary artery disease in men and women presenting with suspected coronary disease. Am J Med 1997;102:350-6. PMID: 9217616
Pryor DB, Shaw L, McCants CB, et al. Value of the history and physical in identifying patients at increased risk for coronary artery disease. Ann Intern Med 1993;118:81-90. PMID: 8416322
Hochman JS, Sleeper LA, Godfrey E, et al. Should we emergently revascularize Occluded Coronaries for Cardiogenic Shock: An International Randomized Trial of Emergency PTCA/CABG-trial design. The SHOCK Trial Study Group. Am Heart J 1999;137:313-21. PMID: 9924166
Assessment for cadiogenic shock on physical exam
Laboratory testing for cardiac biomarkers of necrosis
Jaffe AS, Babuin L, Apple FS. Biomarkers in acute cardiac disease: the present and the future. J Am Coll Cardiol 2006;48:1-11. PMID: 16814641
Lindahl B, Venge P, Wallentin L. Early diagnosis and exclusion of acute myocardial infarction using biochemical monitoring. The BIOMACS Study Group. Biochemical Markers of Acute Coronary Syndromes. Coron Artery Dis 1995;6:321-8. PMID: 7655716
Non-invasive radiologic evaluation of acute chest pain
American College of Radiology. Cardiac Imaging Guidelines. Acute Chest Pain – Suspect Myocardial Ischemia. 2005.
Amanullah AM, Bevegard S, Lindvall K, Aasa M. Assessment of left ventricular wall motion in angina pectoris by two-dimensional echocardiography and myocardial perfusion by technetium-99m sestamibi tomography during adenosine-induced coronary vasodilatation and comparison with coronary angiography. Am J Cardiol 1993;72:983-89. PMID: 8213598
Colon PJ, Guarisco JS, Murgo J, Cheirif J. Utility of stress echocardiography in the triage of patients with atypical chest pain from the emergency department. Am J Cardiol 1998;82:1282-4, A10. PMID: 9832109
Ioannidis JP, Salem D, Chew PW, Lau J. Accuracy of imaging technologies in the diagnosis of acute cardiac ischemia in the emergency department: a meta-analysis. Ann Emerg Med 2001;37:471-7. PMID: 11326183
Lim SH, Sayre MR, Gibler WB. 2-D echocardiography prediction of adverse events in ED patients with chest pain. Am J Emerg Med 2003;21:106-10. PMID: 12671809
Templeton PA, McCallion WA, McKinney LA, Wilson HK. Chest in the accident and emergency department: is chest radiography worthwhile? Arch Emerg Med 1991;8:97-101. PMID: 1888421
Udelson JE, Beshansky JR, Ballin DS, Feldman JA, Griffith JA, Griffith JL, Hander J, et al. Myocardial perfusion imaging for evaluation and triage of patients with suspected acute cardiac ischemia: a randomized controlled trial. JAMA 2002;288:2693-700. PMID: 12460092
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Discharge and Transition
Mulley AG, Thibault GE, Hughes RA, Barnett GO, Reder VA, Sherman EL. The course of patients with suspected myocardial infarction: the identification of low-risk patients for early transfer from intensive care. N Engl J Med 1980; 302:943-8. PMID: 7360201
Hyde CJ, Robert IE, Sinclair AJ. The effects of supporting discharge from hospital to home in older people. Age Ageing 2000; 29:271-279. PMID: 10855913
Shepperd S, Parkes J, McClaran J, Phillips C. Discharge planning from hospital to home Cochrane Database Systematic Rev 2003; The Cochrane Library (ISSN 1464-780X). PMID: 14973952
Parker SG, Peet SM, McPherson A, Cannaby AM, Abrams K, Baker R, Wilson A, Lindesay J, Parker G, Jones DR. A systematic review of discharge arrangements for older people. Health Technology Assessment 2002; 6:1-183. PMID: 12065067
Phillips CO, Wright SM, Kern DE, Singa RM, Shepperd S, Rubin HR. Comprehensive discharge planning with post-discharge support for older patients with congestive heart failure: a meta-analysis. JAMA 2004; 291:1358-1367. PMID: 15026403
Coleman EA, Parry C, Chalmers S, Min SJ. The care transitions intervention: results of a randomized controlled trial. Arch Int Med 2006; 166:1822-8. PMID: 17000937
Coleman EA, Mahoney E, Parry C. Assessing the quality of preparation for posthospital care from the patient's perspective: the care transitions measure. Med Care. 43:246-55, 2005. PMID: 15725981
Coleman EA, Smith JD, Frank JC, Min S-J, Parry C, Kramer AM. Preparing patients and caregivers to participate in care delivered across settings: The care transitions intervention. J Am Geriatr Soc. 2004; 52:1817-1825. PMID: 15507057
Smith JD, Coleman EA, Min SJ. A new tool for identifying discrepancies in postacute medications for community-dwelling older adults. Amer J Geriatr Pharmacotherapy. 2:141-7, 2004. PMID: 15555490
The Care Transitions Intervention: A Patient-Centered Approach to Facilitating Effective Transfers Between Sites of Geriatric Care. Home Health Services Quarterly, 2003; 22:1-18.
Coleman EA, Berenson RA. Lost in transition: challenges and opportunities for improving the quality of transitional care. Ann Intern Med. 2004 Oct 5;141(7):533-6. PMID: 15466770 [PubMed - indexed for MEDLINE]
Coleman EA, Min SJ, Chomiak A, Kramer AM. Posthospital care transitions: patterns, complications, and risk identification. Health Serv Res. 2004 Oct;39(5):1449-65. PMID: 15333117 [PubMed - indexed for MEDLINE]
Coleman EA, Boult C; American Geriatrics Society Health Care Systems Committee. Improving the quality of transitional care for persons with complex care needs.J Am Geriatr Soc. 2003 Apr;51(4):556-7. No abstract available. PMID: 12657079 [PubMed - indexed for MEDLINE]
Coleman EA. Falling through the cracks: challenges and opportunities for improving transitional care for persons with continuous complex care needs.J Am Geriatr Soc. 2003 | 
