Response to Letter 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”

Abstract

CorrespondenceWe appreciate the interest of and comments by Drs Argulian and Messerli on our recently published study.1 Defining inclusion and exclusion criteria, along with dose selection of the administered pharmacological therapy, is critical in the early stages of a clinical trial design. The scientific method strongly recommends performing a profound bibliographic research in this regard, and for this purpose, we carefully reviewed previously conducted trials on the use of β-blockers in the setting of ST-segment-elevation acute myocardial infarction, taking note of the strengths and weaknesses of each of them.Thus, for the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction (METOCARD-CNIC) trial, we randomized anterior myocardial infarctions revascularized by primary angioplasty in <6 hours from symptom onset because this is the population that most benefits from any cardioprotective intervention. More important, and for safety reasons, we designed a trial to recruit patients with no obvious contraindications for the administration of intravenous metoprolol. Because β-blockers are clearly contraindicated in the acute phase of severe heart failure, patients in Killip-Kimball classes III and IV were strictly excluded from randomization, 2 fulfilling the primum non nocere principle. Patients randomized to intravenous metoprolol received up to three 5-mg boluses of metoprolol tartrate 2 minutes apart, following the same scheme as that in the Thrombolysis in Myocardial Infarction (TIMI) II-B trial, 3 closely checking for the presence of contraindications-heart rhythm and rate, PR-interval duration, blood pressure, and clinical examination-before the administration of every single bolus. Similarly, the dose and timing for oral metoprolol after reperfusion were selected according to current recommendations. 4 Thus, an initial low dose of 25 mg metoprolol twice a day was initiated in the vast majority of the patients included in the trial within the first 24 hours of admission and was carefully titrated according to clinical judgment.The increase in mortality observed in patients with initial systolic blood pressure <120 mm Hg or Killip-Kimball class III in the Clopidogrel and Metoprolol in Myocardial Infarction Trial (COMMIT) trial 5 is one of the main reasons why clinical practice guidelines do not emphasize early intravenous β-blocker initiation in ST-segmentelevation myocardial infarction. These patients were systematically excluded from our trial; consequently, prereperfusion administration of intravenous metoprolol did not increase the incidence of major adverse cardiac events in our study. This reinforces the contraindications for intravenous β-blocker therapy in patients with overt heart failure but supports its use in the population that can potentially benefit most from this inexpensive, safe, and effective intervention.Although there are other important differences between the METOCARD-CNIC trial and previously conducted studies evaluating the effect of β-blockers in the settin...

Brain–heart interaction after acute ischemic stroke

“…Anticonvulsant agents, neuroleptics, and many other drugs commonly used in the ICU may prolong the QTc interval [82]; particular attention to this possible adverse effect must be paid in AIS patients. It is generally agreed that beta blockers are the cornerstone of medical therapy to reduce sympathetic hyperactivity and prevent cardiac remodeling after myocardial infarction [83], but the literature is inconclusive concerning their use in AIS patients. Beta blockers and alpha-2 antagonists demonstrated positive results for acute treatment of hypertension, while angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are good options for chronic blood pressure control after AIS [82].…”

Impact of Left Ventricular Hypertrophy on Troponin Release During Acute Myocardial Infarction: New Insights From a Comprehensive Translational Study

“…Patients with first anterior STEMI presenting early (<6 hours) and undergoing primary angioplasty were recruited within the METOCARD-CNIC trial. 13,14 A prespecified analysis within this trial was the study of the association between cTnI/total CK and CMR-measured LVH, IS, and LVEF. Inclusion/exclusion criteria can be found elsewhere.…”

“…15 Serial cTnI and total CK measurements were taken in 140 patients, and data from these patients were used for the current analysis. All patients underwent CMR studies at 5 to 7 days (1 week) 13 and 6 months 14 after STEMI. This study was approved by the ethics committee, and patients signed informed consent.…”

β‐Blocker Therapy Prior to Admission for Acute Coronary Syndrome in Patients Without Heart Failure or Left Ventricular Dysfunction Improves In‐Hospital and 12‐Month Outcome: Results From the GULF‐RACE 2 (Gulf Registry of Acute Coronary Events‐2)

“…The long-term cardiovascular outcome associated with BB prescription following an ACS is controversial. Although BB were proven to decrease the infarct size and limit the LV remodeling on the short-and medium term, 1,22 several studies questioned its use in the long term, especially in the past 2 decades when reperfusion and secondary prevention have become a common clinical practice. In the COMMIT (Clopidogrel and Metoprolol in Myocardial Infarction) trial that randomized >45 000 patients with ACS to metoprolol versus placebo, the co-primary end point of decreased mortality was not met, whereas only the risk of reinfarction and VF was decreased at the price of an excess cardiogenic shock.…”