What are the functions of metoprolol and enoxaparin in the management of myocardial infarction?

Functions of Metoprolol and Enoxaparin in Myocardial Infarction Management

Metoprolol in MI

Metoprolol reduces mortality, reinfarction, and ventricular fibrillation when initiated orally in hemodynamically stable STEMI patients, but intravenous administration increases cardiogenic shock risk and should be avoided in most cases. 1

Primary Benefits in MI

• Mortality reduction: Long-term oral beta-blocker therapy after STEMI is well established for reducing mortality 1
• Prevention of reinfarction: Metoprolol reduces reinfarction by 5 per 1000 patients treated 1
• Ventricular fibrillation prevention: Reduces VF by 5 per 1000 patients 1
• Secondary prevention: Post-MI beta-blockade provides 34% reduction in all-cause mortality, 38% decrease in cardiovascular mortality, and 41% decrease in sudden death 2

Critical Evidence Against Routine IV Use

The COMMIT/CCS-2 trial fundamentally changed practice by demonstrating that early IV metoprolol (followed by oral administration) in 45,852 patients with suspected infarction did not improve survival compared to placebo 1. While fewer patients experienced reinfarction or VF with metoprolol, this benefit was completely counterbalanced by a significant increase in cardiogenic shock—specifically 11 additional cases of cardiogenic shock per 1000 patients treated 1.

Recommended Approach

• Oral initiation preferred: Start oral metoprolol within 24 hours in hemodynamically stable STEMI patients without contraindications 1, 2
• Target dosing: Metoprolol succinate 200 mg daily is the evidence-based target dose, titrated gradually from an initial dose of 12.5-25 mg once daily 2
• Titration schedule: Increase dose every 2 weeks if well tolerated 2

Absolute Contraindications to Metoprolol in MI

• Signs of heart failure, low output state, or decompensated heart failure 1
• Systolic BP <120 mmHg 1
• Heart rate >110 bpm or <60 bpm 1
• PR interval >0.24 seconds or second/third-degree heart block 1
• Active asthma or reactive airways disease 1
• Age >70 years with multiple risk factors for cardiogenic shock 1

Limited Role for IV Metoprolol

IV metoprolol may be considered only in highly selected, low-risk, hemodynamically stable patients presenting with hypertension or ongoing ischemia, using 2.5-5 mg IV bolus over 2 minutes, repeated every 5 minutes as needed, with maximum total dose of 15 mg 1. However, this approach requires extreme caution and continuous monitoring 1.

Enoxaparin in MI

Enoxaparin is superior to unfractionated heparin as anticoagulant therapy in STEMI patients receiving fibrinolysis, reducing death and reinfarction without excessive bleeding when dosed appropriately. 1, 3

Primary Benefits in MI

• Mortality and reinfarction reduction: In the ExTRACT-TIMI 25 trial, enoxaparin significantly reduced the 30-day combined incidence of all-cause mortality plus recurrent nonfatal MI compared to UFH (9.9% vs 12.0%, representing 17% relative risk reduction, P<0.001) 4, 3
• Nonfatal reinfarction prevention: Reduced from 4.5% with UFH to 3.0% with enoxaparin (33% relative risk reduction, P<0.001) 3
• Composite endpoint reduction: Death, nonfatal reinfarction, or urgent revascularization occurred in 11.7% with enoxaparin vs 14.5% with UFH (P<0.001) 3
• Net clinical benefit: The composite of death, nonfatal reinfarction, or nonfatal intracranial hemorrhage occurred in 10.1% with enoxaparin vs 12.2% with UFH (P<0.001) 3

Recommended Dosing in STEMI with Fibrinolysis

• Standard dosing: 30 mg IV bolus, followed by 1 mg/kg subcutaneously within 15 minutes, then 1 mg/kg every 12 hours for up to 8 days (first two subcutaneous doses not to exceed 100 mg) 1, 4
• Elderly patients (≥75 years): No initial IV bolus; reduce subcutaneous dose to 0.75 mg/kg every 12 hours 1, 4
• Renal impairment: 1 mg/kg every 24 hours in patients with estimated creatinine clearance <30 mL/min 4

Use in Primary PCI

Enoxaparin (0.5 mg/kg IV followed by subcutaneous treatment) may be preferred over UFH in primary PCI settings 1. The ATOLL trial showed 17% reduction in the primary composite endpoint (P=0.063) with significant reductions in secondary endpoints, importantly without increased bleeding compared to UFH 1.

Advantages Over Unfractionated Heparin

• More predictable pharmacokinetics with no need for aPTT monitoring 1, 4
• Greater factor-Xa inhibition preventing new thrombin generation 1
• Less protein-binding and platelet activation 1
• Lower rate of thrombocytopenia 1
• Ease of subcutaneous administration 4

Bleeding Considerations

Major bleeding occurred in 2.1% with enoxaparin vs 1.4% with UFH (P<0.001) 3. However, the ASSENT-3 PLUS trial showed that prehospital administration in patients ≥75 years resulted in significant increase in intracranial hemorrhage, emphasizing the importance of age-adjusted dosing 1, 4.

Contraindication

Fondaparinux is not recommended for primary PCI as it was associated with potential harm in the OASIS 6 trial 1.

Combined Antithrombotic Strategy

• Dual antiplatelet therapy: Aspirin plus potent P2Y12 inhibitor (prasugrel or ticagrelor preferred over clopidogrel) should be initiated before or at time of PCI and maintained for 12 months 1
• Anticoagulation duration: Continue enoxaparin until revascularization (if performed) or for duration of hospital stay up to 8 days 1
• Transfer protocol: All patients receiving fibrinolysis should be transferred to PCI-capable center immediately after fibrinolysis 1