ACUTE MI- EVIDENCE-BASED THERAPY

Background: Results of multiple randomized controlled trials are now available to dictate management of acute MI. Despite this, in-hospital mortality from acute MI is still 15%. Standard therapy should include 1) thrombolytics, 2) ASA, 3) Beta-blockers, 4) ACE-I.

Thrombolytics

1. Fibrinolytic Therapy Trialist’s Collaborative Group

a. combined 9 RCTs, total population 58,600

b. IF ST elevations or BBB, 20% decr mort 0-6hrs, 13% decr mort 7-12hrs

c. IF ST elevations or BBB, 30% decr mort 0-1hr, 25% decr mort 2-3hrs, 18% decr mort 4-6hrs

2. Front-loaded tPA vs. Streptokinase (GUSTO): mortality decreased 7.4(6.9%, strokes increased 0.54(0.72%

Antithrombotics

1. ASA (ISIS-2, Antiplatelet Trialists’ Collaboration)

a. considered plt inhibitor, but likely has other mechanisms

b. doses 75-325mg studied

c. short-term benefit: 23% decr mort

d. long-term benefit: 31% decr reinfarction

2. Heparin (GUSTO, GISSI-2, ISIS-3)

a. binds to ATIII, deactivates IIa, Xa, IXa, XIa

b. no mortality benefit, increased bleed risk over ASA and thrombolyis alone

c. still recommended to use heparin w/ FL tPA, although no proven benefit

d. also used for high-risk patients with post-infarct angina

Thrombin inhibitors

1. Hirudin/Hirulog

a. direct thrombin inhibitors

b. early studies (TIMI-5, 6) suggested increased patency when used with tPA compared with heparin w/o incr bleeding. Larger studies have been complicated by excessive bleeding in both treament arms.

Beta-blockers (ISIS-1, MIAMI)

1. decrease HR, BP, contractility, anti-arrhythmic

2. doses studied: 5-15mg IV f/b 100-200mg lopressor QD

3. short-term: 25% decr mort in first 2 days

4. long-term: 25% decr mort and reinfarction

ACE-inhibitors (CONSENSUS II, GISSI-3, ISIS-4, CCS-1)

1. reduce afterload and preload, prevent dilation and remodeling

2. doses studied: captopril 6.25mg f/b 12.5-50mg TID

3. short-term: decr mort 6.5-12% in unselected pop

4. long-term: decr mort 19%, CHF 37%, recur MI 25% in high risk pop (EF<40%)

Nitrates (ISIS-4, GISSI-3)

1. decrease preload, afterload, dilate coronary arteries

2. no proven mortality benefit

3. reserved for high-risk patients: CHF, large anterior MI, post-infarct angina

Calcium channel blockers (TRENT, SPRINT, MDPIT, DAVIT)

1. decr BP, contractility

2. reduced risk of reinfarction, but NO mortality benefit

3. incr mort w/ short-acting agents

Antiarrhythmics: decr arrhythmias, but inc mortality 15-38%

Magnesium (LIMIT-2, ISIS-4): Ca antagonist, vasodilator, plt inhibitor, antiarrhythmic. No mortality benefit.

Glucose, Insulin, Potassium: early studies suggest benefit.

Yusuf et al. European Heart Journal. 17(Suppl F): 16-29, 1996.