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.