Myocardial infarction: the first 24 hours – includes patient information sheet

Myocardial infarction: the first 24 hours – includes patient information sheet – Cover Story

Thomas Gavagan

Myocardial infarction is the most common cause of death in the United States. Rapid postinfarction intervention in the first 24 hours decreases mortality. Treatment modalities are rapidly evolving as new data from basic science research and clinical trials become available. Rapid thrombolysis, accurate criteria for diagnosis and administration of effective adjunctive therapy are crucial in preventing complications of myocardial infarction. Initial measures in the emergency department include intravenous access, accurate history and physical assessment, placement of oxygen, electrocardiography, use of aspirin and nitrates, and consideration of thrombolysis or angioplasty in appropriate candidates, optimally within one to two hours of myocardial infarction. After hospital admission, additional adjunctive treatment, including beta blockers, angiotensin-converting enzyme inhibitors and anticoagulation, can be instituted.

The most critical factor in prehospital care of a patient with myocardial infarction is reducing the time from infarction to thrombolysis. Delay in thrombolytic treatment is linearly related to increased mortality. Initiating treatment within the first hour after the onset of symptoms (the “golden” hour) reduces mortality, prevents myocardial damage and affords the opportunity to treat cardiac arrest. Benefit of treatment still remains after two hours and even up to 12 hours, particularly in patients with intermittent coronary occlusion.

Delayed therapy is related to patient factors and to the emergency medical services system, as well as delays within the emergency department. The National Heart Attack Alert Program (NHAAP)l was developed by the National Heart, Lung, and Blood Institute to promote rapid identification and treatment of myocardial infarction. The program includes representation from many organizations, including the American Academy of Family Physicians. The program participants analyzed the stages from the onset of myocardial infarction and identified the components of delay, including patient delay in the decision to seek care, travel to the hospital and time to initiation of thrombolytic agents in the emergency department. The National Heart, Lung, and Blood Institute recommends that thrombolytic treatment begin within 30 to 60 minutes of hospital arrival.[1]

Family physicians should be involved in minimizing delays at each stage. Patients should be educated to recognize symptoms of myocardial infarction so they do not delay in seeking immediate care. Systems facilitating rapid referral to emergency services for administration of thrombolytic agents should include training clinic staff, providing night-call systems and, in some communities, prehospital administration of thrombolytic agents.[2,3] Protocols should be established in collaboration with emergency physicians and cardiologists to minimize such reasons for delay as the patient attempting to contact the primary care physician and/or cardiologist. Finally, family physicians who work in emergency-department settings must be familiar with the principles of thrombolysis and use of the hospital protocol.

Immediate Emergency Management

Immediate hospital management should emphasize the following treatment goals: rapid diagnosis of myocardial infarction, assessment and stabilization of hemodynamic status, relief of ischemic pain and screening candidates for eligibility for thrombolysis.[4] On arrival in the emergency department and after triage, the following staff activities should begin simultaneously: placement of intravenous access; initiation of cardiac monitoring; administration of oxygen; administration of one 325-mg aspirin tablet, chewed, and topical or sublingual nitrates; blood studies, and electrocardiography.

Meanwhile, the physician should conduct a rapid history and physical assessment to clinically diagnose infarction and screen for its complications, including cardiogenic shock, arrhythmia and congestive heart failure. Rapid completion of these activities will then allow consideration of thrombolysis or angioplasty by protocol, optimally leading to treatment within one to two hours. After hospital admission, additional adjunctive treatment, including beta blockers, angiotensin-converting enzyme (ACE) inhibitors and anticoagulation can be instituted.

Criteria for Diagnosis

The most important criterion in the diagnosis of myocardial infarction is the history: characteristic pain and associated symptoms, including duration and radiation of pain, shortness of breath, nausea and diaphoresis.[5] The presence or absence of risk factors, including smoking, hypertension, diabetes, hyperlipidemia and previous cardiac history, affects the pre- and postevent probability of myocardial infarction.[6] Because failure to diagnose myocardial infarction represents a common source of litigation, clinical decisionmaking algorithms have been created to reduce the diagnostic error rate.[7,8]

Biochemical markers are released into the blood stream after damage to the myocardial cell. The first marker to become abnormal is the creatine kinase (CK) level, which becomes elevated in six to eight hours and peaks in 12 to 24 hours (Table 1). The CK-MB fraction becomes positive at 12 to 20 hours (eight to 14 hours with thrombolysis). Generally, CK-MB activity exceeds 5 percent of total CK activity in patients with acute myocardial infarction (specificity: greater than 95 percent). New tests for subforms of CK-MB (MB1 and MB2), as well as myoglobin and troponin, are increasingly becoming available in emergency department settings.[9] The ratio (MB1/MB2) is very sensitive and specific for the diagnosis of myocardial infarction.

[TABULAR DATA 1 OMITTED]

ELECTROCARDIOGRAPHY / ECHOCARDIOGRAPHY

The use of electrocardiography (ECG) in patients with acute myocardial infarction has been controversial. ST-segment elevation is consistent with myocardial infarction but is a poor predictor of subsequent Q wave evolution. In the first 24 hours, serial ECGs are often required to document the evolution of changes that may become consistent with a diagnosis of acute myocardial infarction. In some emergency departments, echocardiography is used to look for wall motion abnormalities and to identify patients requiring hospitalization.

OTHER DIAGNOSES

The physician should remain alert for other cardiovascular disorders, as well as gastrointestinal, musculoskeletal, pulmonary and psychogenic problems, in patients presenting with myocardial infarction-like symptoms. Cardiac conditions include valvular disease (aortic stenosis or regurgitation, mitral valve prolapse), hypertrophic cardiomyopathy, pericarditis and pulmonary hypertension. Substance abuse, both acute (cocaine)[10] and remote (cigarette smoking), should be considered. Disorders of the aorta (acute dissection of an aortic aneurysm, syphilitic aortitis) should also be considered.

Gastrointestinal causes of myocardial infarction-like symptoms often relate to the stomach or the esophagus (spasm, esophagitis, perforation, ulcer disease). In addition, pancreatitis and cholecystitis may be confused with myocardial infarction. Musculoskeletal disorders also frequently present as chest pain; the most common of these are costochondritis, cervical or thoracic spine disease, and herpes zoster. Associated psychogenic factors, such as hyperventilation, anxiety and depression, should be considered. Pulmonary infection, embolism and neoplasm occur frequently, as do pneumothorax, mediastinitis and pleurisy.

Complications in the First 24 Hours

The most frequent complications occurring in the first 24 hours after myocardial infarction are congestive heart failure, cardiogenic shock, right ventricular infarction, free-wall rupture and tamponade, acute valvular dysfunction (especially mitral regurgitation) and arrhythmia. The clinical features to look for include rales and increased jugular venous pressure (congestive heart failure), Beck’s triad (jugular venous distention, muffled heart sounds and pulsus paradoxus–classic for tamponade but usually not all present), and a new murmur, indicating the possibility of mitral regurgitation.

Clinical and hemodynamic stages following myocardial infarction can be distinguished, often with the Killip classification (Table 2). In-hospital mortality in patients with an adequate cardiac index (over 2.2) increases from 3 to 9 percent when the pulmonary capillary wedge pressure (PCW) is over 18. In more severe cases, when the cardiac index is less than 2.2, the mortality risk increases from 18 percent (PCW less than 18) to a dangerous 60 percent. In the post-thrombolysis era, these predictors of mortality may not be accurate. A recent analysis after thrombolysis found that age, lower systolic blood pressure, elevated heart rate and anterior infarction, as well as Killip classification, are related to increased mortality.[11]

[TABULAR DATA 2 OMITTED]

Thrombolysis

MECHANISM OF ACTION

The longstanding debate as to whether myocardial infarction is caused predominately by atherosclerosis or thrombosis has been resolved. Infarction is now thought to result from a thrombus obstructing a coronary artery (occlusion in up to 90 percent of cases) at the site of a ruptured atherosclerotic plaque. Best treatment results are obtained if thrombolytic agents are administered in the first 100 minutes, although definite benefit remains within the first three hours and even up to 12 hours.[12, 13] Studies of early thrombolytic therapy demonstrated a 16 to 27 percent decrease in mortality (from 9.8 to 7.2 percent at one month), and even better results were achieved with the addition of aspirin.[14]

CRITERIA FOR INITIATION OF THROMBOLYTIC THERAPY

In clinical trials, a conservative standard has been used to select patients for thrombolysis (Table 3). While these trials have shown a clearly beneficial effect, only one-third of patients with myocardial infarction met criteria for randomization to receive treatment. For the other two-thirds (30 percent arriving too late, 15 percent too old, 10 percent with equivocal ECG findings, and 15 percent with contraindications),[1] it is unknown if thrombolysis is beneficial. Data suggest that therapy six to 12 hours after myocardial infarction may be beneficial. Older patients, who are at higher risk, may have a greater benefit.[15] Thrombolysis appears to have no benefit in patients with unstable angina. Table 4 lists the relative and absolute contraindications to thrombolytic therapy.

TABLE 3

Indications for Thrombolysis

Chest pain consistent with angina (< 12 hours)

Electrocardiographic changes

ST elevation (1 mm) on two contiguous limb leads

ST elevation (2 mm) on two contiguous

precordial leads

New left bundle branch block

Absence of contraindications

TABLE 4

Absolute and Relative Contraindications to Thrombolytic Therapy

Absolute contraindications

Active internal bleeding

Intracranial neoplasm or recent head trauma

Prolonged, traumatic CPR

Suspected aortic dissection

Pregnancy

History of hemorrhagic or recent nonhemorrhagic CVA (within

the past six

months)

Severe persistent hypertension (greater than 180 systolic

or greater than 110

diastolic), despite pain relief and initial medication

Relative contraindications

Recent trauma or major surgery (within the last two months)

Initial blood pressure greater than 180 systolic or

110 diastolic (controlled

by medical treatment)

Active peptic ulcer or guaiac-positive stools

Remote history of stroke, tumor, injury or brain surgery

Known bleeding disorder or current use of warfarin (Coumadin)

Significant liver dysfunction or renal failure

Exposure to streptokinase (Kabikinase, Streptase)

or anistreplase (Eminase)

during the preceding 12 months

(contraindication applies to these agents

only)

Known cancer or illness with possible

thoracic, abdominal or intracranial

abnormalities

Prolonged CPR

CPR = cardiopulmonary resuscitation;

CVA = cerebrovascular accident.

Adapted from Billi JE,

Cummins RO, eds. Instructor’s manual for advanced cardiac

life support. Dallas: American Heart Association, 1994.

More recently, the Antiplatelet Trialists Collaboration,[30-32] which included 145 trials and 70,000 patients, showed a decrease in rates of repeat stroke after cerebrovascular accident or transient ischemic attack, decreased rates of death and myocardial infarction after coronary artery bypass grafting or angioplasty, and less occlusion of peripheral vessels with arteriovenous fistulas or after peripheral revascularization, as well as a decreased incidence of myocardial infarction and reinfarction. Newer antiplatelet drugs related to snake venom, which inhibit glycoprotein IIb/IIIa receptors, are being studied and have shown benefit in preliminary trials.[33]

HEPARIN AND ANTITHROMBIN DRUGS

Heparin has a beneficial effect in the treatment of myocardial infarction by accelerating the formation of complexes by antithrombin III, which block thrombin and other coagulation factors. The drug is particularly useful if no thrombolytic agent is given or with primary thromboplasty. Use of alteplase requires the use of intravenous heparin to prevent reocclusion. In GISSI-2[25] and-ISIS 3,[29] subcutaneous heparin was not helpful when used with streptokinase, and most centers now use intravenous heparin. However, in the GUSTO trial,[19] the best results for coronary patency and mortality were found with accelerated administration of alteplase and intravenous heparin.

Combined use of intravenous heparin and streptokinase did not produce additional survival benefit. Newer thrombin inhibitors such as hirudin, originally obtained from leeches but now obtained from recombinant DNA,[34] are being investigated. Excessive heparinization may lead to bleeding, with intracranial bleeding being the greatest concern. The partial thromboplastin time (PTT) should be kept under 85 seconds, and heparin should not be used if bleeding or thrombocytopenia are present, or if the patient is allergic to heparin.

PREVENTION OF REOCCLUSION

In some studies, the long-term use of warfarin (Coumadin) has shown some benefit, especially in patients with large anterior myocardial infarctions, heart failure with reduced ejection fraction, left ventricular mural thrombus or aneurysm, or atrial fibrillation.

In summary, the American College of Cardiology4 recommends the following: administration of a thrombolytic agent; immediate administration of aspirin, 160 to 325 ma, and administration of intravenous heparin to produce an activated PTT of 1.5 to 2 times control for 24 to 72 hours during and after thrombolysis.

Arrhythmias and Conduction Disturbances

ARRHYTHMIA TREATMENT AND PREVENTION

The arrhythmias most often associated with acute myocardial infarction are supraventricular tachycardia, including sinus tachycardia, atrial fibrillation and flutter, and ventricular tachyarrhythmias, including ventricular fibrillation. One-half the cases of primary ventricular fibrillation are unassociated with warning arrhythtnias.3536

In the past, lidocaine (Xylocaine) was used prophylactically in an attempt to reduce mortality by reducing the risk of primary ventricular fibrillation, but fatal asystolic events still occurred. A meta-analysis of studies of treatment with lidocaine found increased mortality rates, leading to elimination of its routine use.[37] Lidocaine is still the agent of choice for severe ventricular arrhythmias, however. The use of other antiarrhythmic agents, including quinidine (Cardioquin) and procainamide (Pronestyl), has not been successful. New studies show a possible benefit with the use of amiodarone (Cordarone).[38] More complications were found in patients given encainide (Enkaid) or flecainide (Tambocor) than in those given placebo.[39]

CONDUCTION DISTURBANCES

Common arrhythmias occurring in the first 24 hours after myocardial infarction include first-degree AV block, second-degree AV block, complete AV block, bundle branch block (left more ominous than right) and bradyarrhythmias. The development of primary ventricular fibrillation has been associated with doubling of hospital mortality despite thrombolysis.[35] The ECG changes of acute myocardial infarction may not be apparent in the presence of left bundle branch block. A temporary pace maker is needed in patients with type II-second-degree AV block, complete AV block or symptomatic bradycardia. Table 6 lists the special situations requiring temporary pacing. High-risk patients warranting temporary pacing include those with new onset of bundle branch block or alternating bundle branch block.

[TABULAR DATA 6 OMITTED]

Adjunctive Therapy: Beta Blockers, ACE Inhibitors

BETA BLOCKERS

Several pharmacologic maneuvers are available to decrease myocardial oxygen demand and limit infarct size in the first three to six hours. Beta blockers have been definitely shown to reduce mortality, most conclusively in the Gotenberg Metoprolol Trial[40] and in ISIS-I.[41] Efficacy is less clear when beta blockers are used in conjunction with thrombolysis in the first 12 hours. When used with aspirin, warfarin and ACE inhibitors, beta blockers are effective by promoting left ventricular remodeling and preventing recurrent ischemia.

Beta blockade decreases myocardial oxygen demand by decreasing heart rate and myocardial contractility. Some beta blockers also appear to have intrinsic antiarrhythmic properties and have been shown to decrease the incidence of ventricular fibrillation in patients with acute myocardial infarction. While mild left ventricular failure is not an absolute contraindication to the use of beta blockers, a short-acting drug, such as esmolol (Brevibloc), could be considered.

Results from long-term trials of beta blocker prophylaxis in postmyocardial infarction patients has been very significant and impressive. The Beta Blocker Heart Attack Trial[47] was terminated earlier than scheduled because of the significant reduction in mortality in the patients treated with propranolol–39 percent at one year and 28 percent at three years.

ACE INHIBITORS

Recently, much interest has focused on the use of ACE inhibitors after myocardial infarction. Studies have shown a reduction of ventricular dilation and coronary heart failure, as well as a reduction in reinfarction and total mortality. The SAVE[43] study used captopril to lower mortality after myocardial infarction with ejection fraction less than 40 percent. The CONSENSUS II study[44] found no benefit with enalapril. The large GISSI-3 trial,[45] using lisinopril, and the ISIS-4 trial,[46] using captopril, showed a reduction in mortality. The SMILE study[47] used zofenopril for six weeks, leading to a 25 percent decrease in mortality, an effect that continued through the first year. It is unclear from the literature if ACE inhibitors should be used routinely or reserved for use in patients with early signs of coronary heart failure.[48]

MAGNESIUM

Several studies found fewer arrhythmias and conduction disturbances, less coronary heart failure and better survival in patients treated with magnesium, compared with patients given placebo.[47] Recent clinical studies, however, have shown less favorable results. Magnesium is not helpful when used in addition to thrombolytic agents and can lead to bradyarrhythmias. Magnesium is contraindicated in patients with renal insufficiency.

CALCIUM CHANNEL BLOCKERS

Since a meta-analysis in 198949 showed no reduction in mortality, calcium channel blockers have not routinely been used in post-myocardial infarction patients. One study[50] did show a benefit from verapamil if left ventricular function was good. Diltiazem has been shown to reduce reinfarction following non-Q wave myocardial infarction in patients without pulmonary congestion or severe left ventricular dysfunction, but this was a nonprospectively selected subset analysis. There are possible adverse effects of diltiazem in patients with reduced left ventricular ejection fraction. A recent study found an increased risk of myocardial infarction in hypertensive patients taking short-acting calcium channel blockers.[51]

NITRATES

Oral, sublingual and intravenous nitrates have been routinely used without clear proof of benefit in clinical trials (ISIS-IV).[46] Nitrates, particularly when administered intravenously, may be useful in patients with sustained chest pain, severe hypertension and acute infarction. The usual intravenous dosage is 5 to 10 [mu]g per minute for 24 to 36 hours. After titration, the patient is switched to an oral maintenance dosage. Blood pressure should be monitored closely for signs of hypotension. Use of oral nitrates should be avoided if the patient’s mean arterial pressure is less than 80.

In selected severe cases, other modalities such as emergency angioplasty, afterload manipulation, intravenous nitroglycerin and the intra-aortic balloon pump can be used.

Figure 1 summarizes the emergency management of patients with acute myocardial infarction.

[Figure 1 ILLUSTRATION OMITTED]

REFERENCES

[1.] National Heart Attack Alert Program Coordinating Committee, 60 Minutes to Treatment Working Group. Emergency department: rapid identification and treatment of patients with acute myocardial infarction. Ann Emerg Med 1994:23:311-29. [2.] Weaver WD. Time to thrombolytic treatment: factors affecting delay and their influence on outcome. J Am Coll Cardiol 1995;25(7 Suppl):3S-9S. [3.] Rawles J. Halving of mortality at 1 year by domiciliary thrombolysis in the Grampian Region Early Anistreplase Trial (GREAT). J Am Coll Cardiol 1994;23:1-5. [4.] Guidelines for the early management of patients with acute myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee to Develop Guidelines for the Early Management of Patients with Acute Myocardial Infarction). J Am Coll Cardiol 1990;16:249-92. [5.] Lee TH, Cook EF, Weisberg M, Sargent RK, Wilson C, Goldman L. Acute chest pain in the emergency room. Identification and examination of low-risk patients. Arch Intern Med 1985;145:65-9. [6.] Tierney WM, Roth BJ, Psaty B, McHenry R, Fitzgerald J, Stump DL, et al. Predictors of myocardial infarction in emergency room patients. Crit Care Med 1985;13:526-31. [7.] Eagle KA. Medical decision making in patients with chest pain [Editorial]. N Engl J Med 1991; 324:1282-3. [8.] Lavie CJ, Gersh BJ. Acute myocardial infarction: initial manifestations, management, and prognosis. Mayo Clin Proc 1990;65:531-48. [9.] Stack LB, Morgan JA, Hedges JR, Joseph AJ. Advances in the use of ancillary diagnostic testing in the emergency department evaluation of chest pain. Emerg Med Clin North Am 1995;13:713-33. [10.] Hollander JE. The management of cocaine associated myocardial ischemia. N Engl J Med 1995;333: 1267-72. [11.] Lee K, Woodlief LH, Topol EJ, Weaver WD, Betriu A, Col J, et al. Predictors of 30-day mortality in the era of reperfusion for acute myocardial infarction. Results from an international Trial of 41,021 patients. GUSTO-I investigators. Circulation 1995;91: 1659-68. [12.] Anderson HV, Willerson JT. Thrombolysis in acute myocardial infarction. N Engl J Med 1993;329:703-9. [13.] Fuster V. Coronary thrombolysis–a perspective for the practicing physician [Editorial]. N Engl J Med 1993;329:723-5. [14.] Wilcox RG, von der Lippe G, Olsson CG, Jensen G, Skene AM, Hampton JR. Trial of tissue plasminogen activator for mortality reduction in acute myocardial infarction. Anglo-Scandinavian Study of Early Thrombolysis (ASSET). Lancet 1988;2 (8610):525-30. [15.] Reeder GS. Acute myocardial infarction: enhancing the results of reperfusion therapy. Mayo Clin Proc 1995;70:1185-90. [16.] Gruppo Italiano per lo Studio della Streptochinasi nell’ Infarto Miocardico (GISSI). Long-term effects of intravenous thromobolysis in acute myocardial infarction: final report of the GISSI study Lancet 1987;2(8564):871-4. [17.] 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(8607): 349-60. [18.] AIMS Trial Study Group. Effect of intravenous APSAC on mortality after acute myocardial infarction: preliminary report of a placebo-controlled clinical trial. Lancet 1988;1(8585):545-9. [19.] The GUSTO investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993;329:673-82. [20.] Zijlstra F, de Boer MJ, Hoorntje JC, Reiffers S, Reiber JH, Suryapranata H. A comparison of immediate coronary angioplasty with intravenous streptokinase in acute myocardial infarction. N Engl J Med 1993;328:680-4. [21.] Grines CL, Browne KF, Marco J, Rothbaum D, Stone GW, O’Keefe J, et al. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. The Primary Angioplasty in Myocardial Infarction Study Group. N Engl J Med 1993;328:673-9. [22.] Gibbons RJ, Holmes DR, Reeder GS, Bailey KR, Hopfenspirger MR, Gersh BJ. Immediate angioplasty compared with the administration of a thrombolytic agent followed by conservative treatment for myocardial infarction. The Mayo Coronary Care Unit and Catherterization Laboratory Groups. N Engl J Med 1993;328:685-91. [23.] Lange RA, Hillis LD. Immediate angioplasty for acute myocardial infarction [Editorial]. N Engl J Med 1993;328:726 8. [24.] Goldman L. Cost and quality of life: thrombolysis and primary angioplasty. J Am Coll Cardiol 1995; 25(7 Suppl):38S-41S. [25.] Gruppo Italiano per lo Studio della Sopravvivenza nell’ Infarto Miocardico. GISSI-2: a factorial randomised trial of alteplase versus streptokinase and heparin versus no heparin among 12,490 patients with acute myocardial infarction. Lancet 1990;336: 65-71. [26.] The GUSTO Angiographic Investigators. The effects of tissue plasminogen activator, streptokinase, or both on coronary-artery patency, ventricular function, and survival after acute myocardial infarction. N Engl J Med 1993;329:1615-22 [published erratum appears in N Engl J Med 1994;330: 516]. [27.] Mark DB, Hlatky MA, Califf RM, Naylor CD, Lee KL, Armstrong PW, et al. Cost effectiveness of thrombolytic therapy with tissue plasminogen activator as compared with streptokinase for acute myocardial infarction. N Engl J Med 1995;332:1418-24 [published erratum appears in N Engl J Med 1995;333:267]. [28.] Hennekens CH, O’Donnell CJ, Ridker PM, Marder VJ. Current issues concerning thrombolytic therapy for acute myocardial infarction. J Am Coll Cardiol 1995;25(7 Suppl):18S-22S. [29.] ISIS 3: a randomised comparison of streptokinase vs tissue plasminogen activator vs anistreplase and of aspirin plus heparin vs aspirin alone among 41,299 cases of suspected acute myocardial infarction. ISIS-3 (Third International Study of Infarct Survival) Collaborative Group. Lancet 1992;339: 753-70. [30.] Antiplatelet Trialists’ Collaboration. Collaborative overview of randomised trials of antiplatelet therapy–I: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ 1994;308:81-106. [31.] Antiplatelet Trialists’ Collaboration. Collaborative overview of randomised trials of antiplatelet therapy–II: maintenance of vascular graft or arterial patency by antiplatelet therapy. BMJ 1994;308:159-68. [32.] Antiplatelet Trialists’ Collaboration. Collaborative overview of randomised trials of anhplatelet therapy–III: reduction in venous thrombosis and pulmonary embolism by antiplatelet prophylaxis among surgical and medical patients. BMJ 1994; 308:235-46. [33.] Lefkovits J, Plow EF, Topol EJ. Platelet glycoprotein IIb/IIIa receptors in cardiovascular medicine. N Engl J Med 1995;332:1553-9. [34.] Cannon CP, Braunwald E. Hirudin. initial results in acute myocardial infarction, unstable angina and angioplasty. J Am Coll Cardiol 1995;25(7 Suppl): 308-78. [35.] Volpi A, Maggioni A, Franzosi MG, Pampallona S, Mauri F, Tognoni G. In-hospital prognosis of patients with acute myocardial infarction complicated by primary ventricular fibrillation. N Engl J Med 1987,317:257-61. [36.] Dhurandhar RW,MacMillan RL, Brown KW. Primary ventricular fibrillation complicating acute myocardial infarction. Am J Cardiol 1971;27:347-51. [37.] MacMahon S, Collins R, Peto R, Koster RW, Yusuf S. Effects of prophylactic lidocaine in suspected acute myocardial infarction. An overview of results from the randomized, controlled trials. JAMA 1988;60:1910-6. [38.] Singh SN, Fletcher RD, Fisher SG, Singh BN, Lewis HD, Deedwania PC, et al. Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmia. Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure. N Engl J Med 1995;333:77-82. [39.] The Cardiac Arrythmia Suppression Trial (CAST) Investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrythmia suppression after myocardial infarction. N Engl J Med 1989;321:406-12. [40.] Hjalmarson A, Elmfeldt D, Herlitz J, Holmberg S, Malek I, Nyberg G, et al. Effect on mortality of metoprolol in acute myocardial infarction. A double-blind randomised trial. Lancet 1981;2(8251): 823-7. [41.] First International Study of Infarct Survival Collaborative Group. Randomised trial of intravenous atenolol among 16,027 cases of suspected acute myocardial infarction: ISIS-I. Lancet 1986;2(8498): 57-66. [42.] Lichstein E, Morganroth J, Harrist R, Hubble E. Effect of propranolol on ventricular arrythmia. The beta-blocker heart attack trial experience. Circulation 1983;67(6 Pt 2):15-10. [43.] Pfeffer MA, Braunwald E, Moye LA, Basta L, Brown EJ Jr, Cuddy TE, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med 1992; 327:669-77. [44.] Swedberg K, Held P, Kjekshus J, Rasmussen K, Ryden L, Wedel H. Results of the Cooperative New Scandinavian Enalapril Survival Study II (CONSEN-SUS II). Effects of the early administration of enalapril on mortality in patients with acute myocardial infarction. N Engl J Med 1992;327:678-84. [45.] Gruppo Italiano per lo Studio della Sopravvivenza nel’ Infarto Miocardico. GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Lancet 1994; 343:1115-22. [46.] ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate and intravenous magnesium sulfate in 58,050 patients with suspected acute myocardial infarction. Lancet 1995;345:669-85. [47.] Ambrosioni E, Borghi C, Magnani B. The effect of the angiotensin-converting-enzyme inhibitor zofenopril on mortality and morbidity after anterior myocardial infarction. The Survival of Myocardial Infarction Long-Term Evaluation (SMILE) Study Investigators. N Engl J Med 1995;332:80-5. [48.] Ball SG, Hall AS, Murray GD. Angiotensin-converting enzyme inhibitors after myocardial infarction: indications and timing. J Am Coll Cardiol 1995;25(7 Suppl):42S-6S. [49.] Held PH, Yusuf S, Furberg CD. Calcium channel blockers in acute myocardial infarction and unstable angina: an overview. BMJ 1989;299:1187-92. [50.] Hansen JE Treatment with verapamil during and after an acute myocardial infarction: a review based on the Danish Verapamil Infarction Trials I and II. The Danish Study Group on Verapamil in Myocardial Infarction. J Cardiovasc Pharmacol 1991;18(Suppl 6):S20-5. [51.] Psaty BM, Heckbert SR, Koepsell TD, Siscovick DS, Raghunathan TE, Weiss NS, et al. The risk of myocardial infarction associated with antihypertensive drug therapies. JAMA 1995;274:620-5.

The Authors THOMAS R GAVAGAN, M.D., M.P.H. is division chief of ambulatory and community health at the Cook County Hospital Department of Family Practice, Chicago, where he completed a residency in family practice. He is also assistant clinical professor of family practice at the University of Illinois at Chicago College of Medicine. Dr. Gavagan graduated from Wright State University School of Medicine, Dayton, Ohio. He completed a master of public health degree at the Harvard School of Public Health, Boston.

MANTHANI T. REDDY, M.D., M.P.H. is senior attending physician at Cook County Hospital and medical director of the Dr. Jorge Prieto Health Center, Chicago. After graduating from Osmania Medical College, India, he completed a residency in family practice at Cook County Hospital. Dr. Reddy also completed a master of public health degree at the University of Illinois at Chicago.

Address correspondence to Thomas Gavagan, M.D., M.P.H., Dept. of Family Practice, 1900 W Polk St., Chicago, L 60612.

COPYRIGHT 1996 American Academy of Family Physicians

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