The benefit of beta-blockers is undisputed in patients with heart failure (HF) or left ventricular systolic dysfunction,1,2 and they are recommended in the guidelines for patients after ST-segment elevation myocardial infarction (STEMI) in order to reduce hospitalizations and mortality. The European guidelines3 confer a class IIa recommendation in patients without HF who present normal LVEF, while in the American guidelines4 they have a class I indication for all patients regardless of HF or LVEF. Most trials assessing the effect of beta-blockers after STEMI were carried out several decades ago.5 In the reperfusion era, the benefit of beta-blockers is less clear and seems to be focused on high-risk patients6 such as those with depressed left ventricular ejection fraction (LVEF),7 anterior infarction8 or multivessel disease.9 In cases of preserved LVEF, the evidence for the benefit of beta-blockers is inconclusive.5–13

The aim of our study was to assess the long-term benefit of beta-blockers in a contemporary population of patients discharged in sinus rhythm after STEMI and to study the influence of LVEF on this benefit.

Our data come from the Description of Acute Myocardial Infarction: Management, New Therapies and Evolution (DIAMANTE) registry. The study's methodology has been previously published.14–17 In this paper all patients are included who were 18 years of age or older discharged alive in sinus rhythm after a STEMI18 between January 2010 and April 2015. Exclusion criteria were as follows: presentation more than 24 hours after symptom onset or no reperfusion therapy; out-of-hospital cardiac arrest; need for endotracheal intubation prior to hospital arrival; and non-obstructive coronary artery disease and no evidence of cardiac emboli as the cause of the STEMI. Patients were divided according to the use of beta-blockers at discharge. LVEF was measured by echocardiography and classified as ≤40% or >40%. The primary endpoint was all-cause death during follow-up. Other endpoints assessed included major adverse cardiac events (defined as a composite of all-cause death, reinfarction, vascular complication and hospitalization due to HF) at 30 days after discharge, stroke, and atrial fibrillation during follow-up.

The study complies with the Declaration of Helsinki and was approved by the Ethics Committee of our institution.

A total of 972 patients were included, with a mean age of 62.6±13.5 years, 212 (21.8%) of whom were women. Percutaneous coronary intervention (PCI) was performed in 969 (99.7%, including 112 with rescue PCI) and three (0.3%) received only thrombolytic therapy without rescue PCI. Beta-blockers were prescribed at discharge in 835 patients (85.9%). Baseline characteristics according to beta-blocker prescription are described in Table 1. Patients who did not receive beta-blockers had more comorbidities than those treated with beta-blockers, including chronic obstructive pulmonary disease, anemia, and cancer, and more frequently had inferior STEMI and high-grade atrioventricular block. The independent predictors of beta-blocker prescription at discharge by multivariate analysis are shown in Table 2.

During a mean follow-up of 49.6±24.9 months, 114 patients died (11.7%). Long-term mortality was lower in those who received beta-blockers at discharge than in those who did not. Beta-blocker treatment at discharge was independently associated with lower mortality, but this effect was mainly present in 192 patients with LVEF ≤40% and was not clear in 643 patients with LVEF >40% (Table 3). Survival curves according to the use of beta-blockers at discharge are shown in Figure 1.

Figure 1.

Survival curves according to the use of beta-blockers at discharge. LVEF: left ventricular ejection fraction.

(0.18MB).

In our contemporary cohort of STEMI patients treated with urgent reperfusion therapy and discharged in sinus rhythm, the use of beta-blockers at discharge was associated with better long-term clinical outcomes, particularly in patients with LVEF ≤40%.

The beneficial effect of beta-blocker therapy in STEMI patients is related to reduction in myocardial oxygen demand (by decreasing heart rate, systemic blood pressure, and myocardial contractility) and to increased diastolic perfusion of the ischemic territory, limiting infarct size.7 In the prefibrinolytic era, beta-blocker therapy after STEMI was associated with lower mortality and reinfarction.19 However, in the reperfusion era this beneficial effect is less pronounced.20 In the COMMIT trial,21 metoprolol (intravenous followed by oral administration) had no effect on mortality but reduced the risk of recurrent myocardial infarction at 28 days, in a population without primary PCI and fibrinolysis administered in only 55%. In the last decade the management of patients with STEMI has changed dramatically, including widespread use of primary PCI, efforts to shorten door-to-balloon time, technical and technological improvements in PCI, and widespread use of evidence-based medications such as statins, newer antiplatelet agents, and drugs that inhibit the renin-angiotensin-aldosterone system.7 As a result of these advances, morbidity and mortality after acute STEMI have improved markedly.22,23 Consequently, in some cases, the benefit of beta-blockers may be diluted.

Our data suggest that after STEMI, beta-blocker therapy is associated with better long-term prognosis, particularly with LVEF ≤40%, and this finding is consistent with previous studies.5–7,9 Some studies have demonstrated a benefit of beta-blockers in patients with preserved LVEF.10,11,13 The relatively small sample size of some patient subgroups and the limitations inherent to observational studies may explain these differences.

In a recent study by Dondo et al., 24 the largest analysis to date (comprising >180000 cases) of the effect of beta-blockers on mortality after acute myocardial infarction without HF or depressed LVEF, the use of these drugs was not associated with a lower risk of death. Prior to that study, a meta-analysis of 10 observational studies across 40873 patients suggested a lack of evidence to support the routine use of beta-blockers in all patients with myocardial infarction treated with PCI, but the effect was restricted to reduced LVEF, non-STEMI, and patients with low use of secondary prevention medications.25

The guidelines differ in their recommendations regarding the use of beta-blockers after STEMI. The European guidelines3 confer a class IIa recommendation, level of evidence B, in patients without HF who present normal LVEF, while in the American guidelines4 they have a class I indication for all patients regardless of HF or LVEF. Many patients are prescribed beta-blockers indefinitely after STEMI regardless of LVEF.26 Dondo et al.24 suggest, and we agree, that this practice is probably based on clinical uncertainty.

As beta-blockers are not free of side effects (mild to severe hypotension, bradycardia, dizziness, depression, metabolic disorders, and drug allergy20), and a increasing number of medications is associated with reduced adherence,27 beta-blockers probably should not be mandatory in the discharge treatment of patients with STEMI and LVEF >40%. Randomized trials are needed to resolve questions in this regard.

In patients discharged in sinus rhythm after STEMI treated with PCI, beta-blocker therapy was independently associated with lower mortality in patients with LVEF ≤40%, but the benefit was doubtful in those with LVEF >40%. These findings reinforce the need for large randomized clinical trials in this group of patients.

The authors have no conflicts of interest to declare.