Study Question: Does metoprolol reduce infarct size in STEMI patients when given prior to primary PCI?
Study Description: This multicenter, randomized, single-blind, placebo-controlled trial included patients with ECG-confirmed ST segment elevated myocardial infarction (STEMI) < 4.5 hours from symptom onset. Patients were excluded if they presented with Killip class III or IV infarction, systolic blood pressure < 120 mmHg, PR interval > 240 ms, heart rate < 60 bpm, or active treatment with any β-blocker. Patients received up to three 5-mg doses of IV metoprolol or placebo, and all patients received oral β-blockers post-procedure. The primary endpoint was infarct size, with a subgroup analysis of patients with TIMI grade 0 to 1 flow. Infarct size was quantified by MRI as well as peak and 72-hour AUC of serum creatinine kinase. Investigators also measured myocardial tissue at risk for necrosis shown as edema on MRI and myocardial salvage, which was defined as the difference between myocardium at risk and myocardial necrosis normalized to myocardium at risk. Safety data included the incidence of major adverse cardiac events.
Results: A total of 270 patients were randomized, of which 28 were excluded from any analysis. One hundred and twenty patients received metoprolol, of which 106 were able to complete the MRI; 114 patients received placebo, of which 114 were able to complete the MRI and be included in the primary endpoint analysis. There were no significant baseline differences between the two groups.
Patients who received pre-procedure metoprolol showed a statistically significant decrease in mean infarct size on MRI (25.6 g vs. 32.0 g, p = 0.012), myocardial salvage (34.9% vs. 27.7%, p = 0.024), and increased left ventricle ejection fraction (LVEF; 46.1% vs. 43.4%, p = 0.045). Patients with a TIMI grade 0 to 1 flow benefited from early metoprolol, as evidenced by decreased infarct size (26.7g vs. 34.4g, p = 0.0024) and increased LVEF (45.1% vs. 41.0%, p = 0.0031). Patients with a higher TIMI grade of 2 to 3 did not show a difference in infarct size. Peak CK were lower in the metoprolol group (2397 IU/L vs. 3176 IU/L, p = 0.019) along with AUC (49427 IU/L vs. 62953 IU/L, p = 0.029). The incidence of major cardiac adverse events was similar and infrequent between both groups (7.1% vs. 12.3%, p = 0.21).
Conclusion(s): The administration of intravenous metoprolol prior to primary PCI in anterior wall STEMI reduced the size of infarct and increases LVEF.
Perspective: This was the first study to examine the effect on infarct size of pre-reperfusion STEMI patients treated with primary PCI with no apparent increase in adverse events. Previous studies have either examined patients after thrombolytic therapy or were not adequately powered to detect a difference in infarct size. The difference between subgroups with lower TIMI flow grades suggests that metoprolol decreases the severity of reperfusion injury post-PCI, and may help to decrease the extent of myocardial tissue infarction in STEMI patients without overt symptoms of heart failure. Larger studies may be required to adequately quantify the incidence of adverse events.