HomeCirculationVol. 130, No. 3Letter by Argulian and Messerli Regarding Article, “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” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Argulian and Messerli Regarding Article, “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” Edgar Argulian, MD, MPH Franz H. Messerli, MD Edgar ArgulianEdgar Argulian Mount Sinai St. Luke's Hospital, Division of Cardiology, Mount Sinai Health System, New York, NY Search for more papers by this author Franz H. MesserliFranz H. Messerli Mount Sinai Health Medical Center, Icahn School of Medicine, New York, NY Search for more papers by this author Originally published15 Jul 2014https://doi.org/10.1161/CIRCULATIONAHA.113.006736Circulation. 2014;130:e18To the Editor:The conclusion of the trial by Ibanez et al1 elegantly documents that early intravenous β-blockade with intravenous metoprolol before reperfusion reduced infarct size and increased left ventricular ejection fraction with no excess of adverse events. These findings are in contrast to some extent with the guideline-changing Clopidogrel and Metoprolol in Myocardial Infarction Trial (COMMIT), which examined the role of early β-blocker use in the emergency treatment of myocardial infarction.2 In this large trial, patients received an intravenous injection of 5 mg metoprolol, 2 to 3 minutes later another 5 mg, and similarly a third dose. Only 15 minutes later, 50 mg oral metoprolol was given and repeated every 6 hours during days 0 through 1. From day 2 on, a 200-mg controlled-release metoprolol tablet was given daily. More than 90% of patients assigned to the metoprolol received all 3 intravenous doses, and 86% completed oral treatment. Of note, there was no difference in mortality between the intravenous β-blocker and placebo groups but an excess of cardiogenic shock in the metoprolol arm. Although the investigators should be congratulated for a high protocol adherence rate, the clinical implications of the study are unclear. Common sense clinical practice would rarely consider giving such high doses of metoprolol in a wide range of patients with acute myocardial infarction.Similarly, an excessive dose of β-blockers was used in the Perioperative Ischemic Evaluation (POISE) trial in β-blocker–naïve patients undergoing noncardiac surgery.3 A fixed dose of extended-release metoprolol 100 mg was given 2 to 4 hours before surgery and within 6 hours after surgery. This was followed by a fixed dose of extended-release metoprolol 200 mg daily. Not surprisingly, the risk of hypotension and bradycardia was higher in the intervention group, and there was an increased risk of all-cause mortality and stroke with β-blockers. One may appropriately ask whether the interventions used in COMMIT and POISE reflect common sense clinical practice. To our way of thinking, they do not. In contrast, in the trial of Ibanez et al, a more reasonable β-blockade regimen documented indeed that there may be some benefit in acute myocardial infarction. Without any doubt, evidence from randomized trials certainly remains the gold standard. However, evidence gathered from such trials should not focus on the drug or drug class only but, importantly, should scrutinize the exact dosage and the intervention design to which the patient has been subjected.Edgar Argulian, MD, MPHMount Sinai St. Luke's HospitalDivision of CardiologyMount Sinai Health SystemNew York, NYFranz H. Messerli, MDMount Sinai Health Medical CenterIcahn School of MedicineNew York, NYDisclosuresNone.