Acute Myocardial Infarction
Acute myocardial infarction occurs over in over 500,000 patients in the United States every year. Several pharmacological and mechanical strategies have been developed to help improve the clinical outcomes in acute MI patients.
Diagnosis
The principal diagnostic tool is the patient history.
Correlation with ECG findings as well as blood chemistries helps to
confirm the diagnosis.
Treatment Strategies
Reperfusion
Mechanical
Mechanical revascularization (primary angioplasty)
has been shown to be superior to pharmacological revascularization
with thrombolytic therapy1,2.
There may also be economic advantages to a mechanical strategy. Patency
rates after primary angioplasty are superior to thrombolytic therapy
and in the hands of an experienced operator exceed 90%.
Recent work has centered upon the use of coronary stents in primary angioplasty. PAMI-STENT suggested that primary stenting does not appear to increase the rate of 30-day and 6 month major adverse cardiac events (MACE) and in fact may improve clinical outcomes without the feared risk of stent thrombosis.
Because only about 20% of hospitals in the United States have a cardiac catheterization laboratory and only about half of these sites can perform primary angioplasty, primary angioplasty remains a reperfusion strategy in only a limited number of hospitals.
Pharmacological
Perhaps the greatest benefit of thrombolysis
is its accessibility and ease of use. Thrombolytic studies suggest
that with excellent patency rates of 50-70% the large majority of patients
with acute MI should receive thrombolytics if primary angioplasty is
unavailable. The debate between the use of tPA (and its derivatives)
and streptokinase (SK) essentially boils down to the slight benefit3 of
tPA over SK [6.3% death rate vs. 7.2 %) and the large cost differential
between the two agents.
The benefits of thrombolysis are its ease of use and excellent efficacy; this comes at a cost of a greater risk of bleeding and stroke, which increases significantly in elderly patients. There are few large-scale studies directly comparing thrombolytic therapy to primary angioplasty. The largest, GUSTO IIb4, suggested that there were no significant differences in 30-day MACE between the two strategies; however, the angioplasty arm had the lowest reported patency rate (73%) to date in any primary angioplasty study.
Combination therapy
A recent trial, PACT (Plasminogen-activator
Angioplasty Compatibility Trial), has been initiated studying the use
of ½ dose tPA given in the Emergency Room followed by emergent
angiography. 606 patients were randomized to receive a 2-minute 50mg
IV bolus of tPA or placebo, followed by immediate coronary angiography
and revascularization if indicated. Follow-up included repeat coronary
angiography in 1 week and an exercise treadmill test (ETT) in 6 weeks.
Mean time from study drug to angiography was 49 minutes and superior
TIMI-3 flow rates were seen in the tPA-treated group (32.8%) vs. placebo
(14.8%). The primary angioplasty success rate was not statistically
different. The PACT-2 trial is currently underway.
Adjuvant therapies
Pharmacological
The use of b-blockers, aspirin,
and heparin are well documented. Many studies
are now concentrating on the use of glycoprotein
(GP) IIb/IIIa receptor inhibitors in the setting of an acute MI.
RAPPORT5 examined the use of abciximab (ReoProTM) in the setting of acute MI. 483 patients were enrolled; there was a trend toward improved 7-day, 30-day and 6-month MACE but this difference was not statistically significant. In addition, the heparin dosing was not reduced and this led to a greater incidence of bleeding events in the abciximab arm.
The angiographic results of TIMI-146 were recently published. This study employed abciximab with full or ½ dose tPA, full or ½ dose SK, and alone in 888 patients. Patients receiving tPA were also randomized to low-dose (70 U/kg bolus; 15 U/kg/hr infusion) heparin if they did not receive abciximab or very-low-dose (60 U kg bolus; 7 U/kg/hr infusion) heparin if they received abciximab. Improved TIMI-3 flow rates were exhibited in the patients receving abciximab.
ADMIRAL (Abciximab before Direct angioplasty and stenting in Myocardial Infarction Regarding Acute and Long-term follow-up) was recently published.. At 25 centers in France, 300 patients were enrolled in a double-blind, placebo-controlled fashion. When a diagnosis of acute MI was made, abciximab or placebo were administered in the ambulance, ER, or Cath Lab prior to sheath insertion. Clinical follow-up was at 24 hours, 30 days and 6 months with follow-up angiography at 24 hours and six months.
11% of the patients received study drug prior to arriving at the hospital with 15% in the ER. The results revealed that TIMI-3 flow rates at start of case (21% vs. 10%) and 24 hours (86% vs. 78%) were superior in the abciximab group. In addition, left ventricular performance was better at 24 hours (EF 55% vs. 51%) and 30 days (63% vs. 55%) in the abciximab group. The primary endpoint of combined 30-day MACE (a composite of cardiovascular death, recurrent MI, and urgent target vessel revascularization) were 10.7% in the abciximab group and 20.0% in the control group (p=0.03). There were no differences in major bleeding at 30 days (4.0% vs. 2,6%; p=0.50) but an increase in minor bleeding (6.7% vs. 1.3%, p=0.02).
Recently, the TIrofiban Given in the Emergency Room before Primary Angioplasty (TIGER-PA) pilot study was initiated here at Stanford. This study is a randomized open-label trial. Tirofiban (AggrastatTM) is given as a bolus (10 mg/kg over 3 minutes) and infusion (0.15 mg/kg/min x 24 hours) in the Emergency Room before the patient is brought to the cardiac catheterization laboratory; a control group receives tirofiban in the cath lab. The endpoints for this study include bleeding complications and thrombocytopenia, and 30-day MACE. Enrollment is currently underway; interim results were presented at the ACC2000 conference in Anaheim revealing a higher TIMI-grade flow at angiography with early administration of tirofiban when compared to initiating the drug in the cath lab.
Based upon preliminary data from these trials, the GP IIb/IIIa inhibitors appear to hold promise in the treatment of acute MI.
Mechanical.
Beyond angioplasty and stenting, intra-aortic
balloon counterpulsation (IABP) has been employed
to improve coronary perfusion and reduce afterload. Routine use of
IABP in the setting of an acute MI is not indicated based upon several
small studies. However, in the setting of cardiogenic shock, there
is a clear survival benefit, especially in elderly patients.
Summary
Acute myocardial infarction remains a hotbed of clinical
study. Several new trials examining new strategies to treat acute MI
are currently underway.
References
1. Zijlstra F, de Boer MJ, Hoorntje JCA, reiffers S, Reiber JHC and H Suryapranata (1993). A comparison of immediate coronary angioplasty with intravenous streptokinase in acute myocardial infarction. N Engl J Med 328: 680-4.
2. Grines CL, Browne KF, Marco J et al (1993). A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. N Engl J Med 328: 673-9.
3. The GUSTO Investigators (1993). An international randomized comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 329: 673-82.
4. The Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO IIb) Angioplasty Substudy Investigators (1997). A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator for acute myocardial infarction. N Eng J Med 336: 1621-8.
5. Brener SJ, Barr LA, Burchenal JEB, et al on behalf of the ReoPro and Primary PTCA ORganization and Randomized Trial (RAPPORT) Investigators (1998). Randomized, placebo-controlled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction. Circulation 98:734-41.
6. Antman EM, Giugliano RP, Gibson CM, McCabe CH, Coussement P, Kleiman NS, Vahanian A, Adgey AAJ, Menown I, Rupprecht H-J, Van der Wieken R, Ducas J, Scherer J, Anderson K, Van de Werf F, Braunwald E for the TIMI-14 Investigators (1999). Abciximab facilitates the rate and extent of thrombolysis: results of the thrombolysis in myocardial infarction (TIMI) 14 Trial. Circulation 99: 2720-32.
David P. Lee, M.D.