Long-term oral beta-blocker use decreases mortality after myocardial infarction (MI). Our guidelines recommend initiation of this within 24 hours of acute MI. The benefit of IV beta-blockade is less clear. It is also unknown whether earlier beta blocker administration is better than delayed administration (within 24 hours).
-COMMIT Trial (2005): Early use of IV metoprolol in AMI decreases incidence of ventricular arryhthmias and reinfarctions, but increases cardiogenic shock. Recommends deferral of immediate IV metoprolol until hemodynamic stabilization post-MI. Of note, trial standard of care for AMI was aspirin and fibrinolytics (clearly, not the current standard of care).
-METOCARD-CNIC (2013): Early IV metoprolol prior to reperfusion therapy in patients with acute anterior wall ST-segment Elevation MI (STEMI), without evidence of significant heart failure, reduced infarct size and improved LVEF without significant adverse outcomes in the initial 24 hours. This study excluded patients with Killip Class III/IV heart failure and reperfusion was primarily with percutaneous coronary intervention (PCI).
What is the efficacy and safety of pre-hospital IV metoprolol in anterior STEMI?
All persons 18-80 yo with ischemic-like chest pain for = 4.5 hours and with EKG changes consistent with anterior STEMI
Metoprolol tartrate 5mg IV q2min up to 3x either by EMS or ED prior to prior to reperfusion
Control patients received aspirin and a P2Y12 inhibitor (as did the intervention group), long term beta-blocker therapy was initiated within 24 hours, but not before reperfusion
Primary: Infarct size at 1 week (quantified by cardiac MRI).
Secondary:LVEF at 1 week (quantified by cardiac MRI).
Subanalysis of METOCARD-CNIC, which was a multicenter, randomized, parallel-group, single-blinded trial.
<18 or >80y/o, acute pulmonary edema or cardiogenic shock at presentation, LBBB, PR>240, Type II or III AV block, HR<60bpm, SBP<120mmHg, long-term ongoing B-blocker treatment, active bronchodilator treatment, h/o MI
- Mean infarct size in grams (SD): 23.4 (15) vs. 34.0 (23.7); adjusted difference -11.4 (p=0.09)
- LVEF,% (SD): 48.1 (8.4) vs. 43.1 (10.2); adjusted difference 5.0 (p=0.06)
- Major Adverse Cardiac Events in First 24 hours, No (%): 5 vs 13; Risk difference -11.1 (p=0.31)
147 patients over 25 months in 7 hospitals across 4 regions of Spain (cohort of parent study of patients recruited out-of-hospital)
17/74 patients in intervention group and 11/73 in control group did not follow through to obtain MRI after reperfusion
- Multicenter trial
- Study asked a clear clinical question
- Outcome measures were objective reducing bias
- Intention to treat for efficacy question
- Follow up was complete
- Relatively small sample size
- Unclear if the difference in infarct size was clinically significant
- Did not compare EMS intervention to ED intervention
- EMS in study consisted of physician, nurse, and EMT, which is not standard in all EMS systems
- Risks/benefits of metoprolol cannot be generalized to all beta-blockers
- Poor representation of women (out of proportion to other comparable STEMI trials)
- Relatively high p-values for data
- Lacks long-term outcomes
“EMS intravenous metoprolol administration in acute anterior MI is safe and efficacious during transfer to percutaneous coronary intervention facility in selected patients.”
Use of IV metoprolol in the pre-hospital setting for anterior AMI trends towards short-term improvement in infarct size and LVEF. The relevance of this for long-term, clinically significant outcomes requires more study. Future studies should focus on patient centered outcomes as it’s unclear what the relevance of an 11-gram difference in infarct size is to the patient.
Potential Impact To Current Practice
This study shows potential for early IV metoprolol to have acute benefit in early AMI with minimal risk. However, the small sample size, lack of long-term, or in ED data, limits its applicability to our current practice. Additionally, this study was done using an expanded team of EMS providers, compared to most systems’ resources, and still trends toward increasing pain-to-intervention time.
Use of EMS IV metoprolol in acute anterior MI appears to be safe and effective in the short-term, however, evidence supporting its routine pre-hospital use is not strong enough to implement into our current system.
2 Minute Medicine: The COMMIT Trial: Metoprolol and clopidogrel in patients with acute MI
Ibanez B et al. Effect of early metoprolol on infarct size in ST-segment-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention: the effect of metoprolol in cardioprotection during an acute myocardial infarction (METOCARD-CNIC) trial. Circulation 2013; 128(14): 1495-503. PMID: 24002794
Chen ZM et al. Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 2005; 366(9497): 1622-32. PMID: 16271643