Acute myocardial infarction: Role of beta blocker therapy

Authors:
Robert S Rosenson, MD
Guy S Reeder, MD
Harold L Kennedy, MD, MPH
Section Editor:
Christopher P Cannon, MD
Deputy Editor:
Gordon M Saperia, MD, FACC

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review
process is complete.
Literature review current through: Dec 2017. | This topic last updated: Jul 10,
2017.

INTRODUCTION — For patients with acute myocardial infarction (MI), beta blocker
therapy reduces infarct size and early mortality when started early and lowers the risk
of death when continued long term. (See "Overview of the acute management of ST-
elevation myocardial infarction" and "Overview of the acute management of non-ST
elevation acute coronary syndromes" and "Prevention of cardiovascular disease events
in those with established disease or at high risk".)

This topic will discuss the use of beta blockers in patients with acute MI and focus on
those without heart failure or reduced left ventricular systolic dysfunction [1]. Other
relevant issues regarding beta blockers are discussed elsewhere. (See "Major side
effects of beta blockers" and "Use of beta blockers in heart failure with reduced ejection
fraction" and "Prophylaxis against ventricular arrhythmias during and after acute
myocardial infarction" and "Clinical features and treatment of ventricular arrhythmias
during acute myocardial infarction".)

MECHANISM OF ACTION — Potentially beneficial effects of beta blockers in patients

with acute myocardial infarction (MI) include [2]:

●Decreased oxygen demand due to the reductions in heart rate, blood

pressure, and contractility, and the consequent relief of ischemic chest pain.

●Decreased risk of ventricular fibrillation as suggested by experimental studies

demonstrating an increase in the ventricular fibrillation threshold and by clinical
trials showing a relative risk reduction in sudden cardiac death (eg, 30 to 47
percent) [3-5].

●Decreased automaticity, increased electrophysiologic threshold for activation,

and slowing of conduction.
 ●Bradycardia prolongs diastole and therefore improves coronary diastolic
perfusion and reduces after-depolarizations and triggered activity.

●Reduction in remodeling and improvement in left ventricular hemodynamic

function, depending upon infarct size and the timing of treatment [6-8]. (See
"Cardiac remodeling: Clinical assessment and therapy".)

●Improved left ventricular diastolic function with a less restrictive filling pattern
[9]. (See "Treatment and prognosis of heart failure with preserved ejection
fraction".)

●Slowing of the yearly rate of progression of coronary atherosclerosis in

patients with and without MI, as demonstrated by intravascular ultrasound
evaluation of atheroma volume [10].

●Inhibition of platelet aggregation and thromboxane synthesis [11].

●One or more of the above mechanisms may contribute to a reduction in

reperfusion injury. (See "Reperfusion injury of the heart", section on 'Definition'.)

INDICATIONS — Unless contraindicated (see 'Contraindications' below), we treat all

patients with acute myocardial infarction (MI) with beta blocker therapy. The evidence
supporting the benefit of beta blockers has been obtained primarily from randomized
trials that included predominantly patients with ST-elevation myocardial infarction
(STEMI). There have been no randomized trials specifically addressing the efficacy of
these drugs in non-ST elevation MI (NSTEMI). Observational studies have attempted
to evaluate patients with STEMI and those with NSTEMI.

Many of the relevant studies were performed before the routine use of long-term
antiplatelet and statin therapy. Thus, it is possible that the absolute magnitude of the
mortality benefit from beta blocker described below may be smaller due to the
beneficial impact of these preventative medications as well as the use of reperfusion
therapies.

Evidence from studies of STEMI patients — The use of beta blockers has been
relatively well studied in patients with STEMI treated with no reperfusion, fibrinolytic
therapy, or primary percutaneous coronary intervention.

●No reperfusion – Randomized trials performed before the use of reperfusion

therapy with either fibrinolysis or PCI consistently showed a reduction in
cardiovascular mortality of 10 to 25 percent in patients treated with propranolol,
metoprolol, or atenolol (figure 1) [12-16]. A 1985 meta-analysis of these studies
found a 25 percent reduction in mortality at one year [17]. These patients did
not routinely receive statin therapy or a P2Y12 receptor blocker, both of which
are now standard of care.

●Fibrinolytic therapy – There is no high quality evidence demonstrating a

beneficial impact of long-term beta blocker use in patients treated with
fibrinolytic therapy. Thus, much of the evidence is indirect, coming from the
benefit shown in patients not receiving reperfusion.

The individual studies that evaluated the long-term impact of beta blockade in
patients treated with fibrinolysis were limited by small size [18,19], early
termination [20], observational design [21], or relatively short duration follow-up
[22]. A 1999 meta-analysis, which included trials of patients (n = 24,974) who
did or did not receive fibrinolytic therapy, found that beta blockers reduced the
odds of death by 23 percent (95% CI 15-31) when taken long term, a result
comparable to that seen in patients who received no reperfusion [23].

●Primary PCI – The evidence presented above, supporting long-term beta

blocker use in patients treated with or without fibrinolysis, provides the basis for
a similar recommendation in patients who undergo primary percutaneous
coronary intervention (PCI). Some experts have suggested that the benefit of
beta blockers in this subpopulation may be reduced by the improvement in
outcome afforded by revascularization. There have been no randomized trials
and few observational studies of long-term beta blocker therapy patients treated
with primary PCI [24-26]. Three large observational studies have come to
differing conclusions:

•One observational study evaluated mortality in over 20,000 STEMI

patients (2005 to 2010) [27]. In a propensity-matched analysis of 2650
patients who received and 1325 who did not receive a beta blocker at
discharge, treatment was associated with a lower incidence of all-cause
death (2.8 versus 4.1 percent; adjusted hazard ratio 0.46, 95% CI 0.27-
0.78) during a median follow-up of about one year. In addition, the result
was consistent across all subgroups, including those at relatively low risk,
such as those with left ventricular ejection fraction >40 percent and those
with single-vessel disease.

•In a meta-analysis of 10 observational studies of patients (n = 16,645)

with preserved left ventricular ejection fraction who underwent PCI, there
was no difference in one-year mortality group between those receiving or
not receiving beta blocker [28].
 •A second study evaluated outcomes in 88,522 STEMI and 81,993
NSTEMI patients (2007 to 2013) who did not have heart failure or left
ventricular systolic dysfunction [29]. The overall one-year mortality was 5.2
percent. After adjustment, there was no significant difference in mortality
between those with and without beta blocker use in either STEMI or
NSTEMI groups.

INITIAL THERAPY — For patients without contraindications, we treat all patients with
an oral beta blocker within the first 24 hours after diagnosis. There is no consistent
evidence of benefit from the use of intravenous beta blocker use prior to primary
percutaneous coronary intervention. We reserve the intravenous route principally for
patients with refractory angina and/or hypertension who have ongoing ischemia prior to
percutaneous coronary intervention (PCI) in whom there is no hemodynamic instability,
risk for shock, heart failure, or other contraindications.

LV dysfunction/heart failure — Some of the studies discussed directly below were

performed before the availability of angiotensin converting enzyme inhibitors and
generally did not assess patients with asymptomatic left ventricular dysfunction or heart
failure [13,15,16]. They were also performed before the strong beneficial effects of beta
blockers in heart failure were demonstrated. The use of beta blockers in patients with
heart failure due to systolic dysfunction is discussed elsewhere. (See "Use of beta
blockers in heart failure with reduced ejection fraction".)

Fibrinolytic therapy — While, in the aggregate, the available evidence does not
support routine, early initiation of intravenous beta blockade in patients treated with
fibrinolytic therapy, we do recommend oral therapy. This recommendation for these
patients is based on the overall benefit of beta blockers. (See 'Indications' above.)

Three randomized trials (1989, 1991, and 1993) of ST-elevation myocardial infarction
(STEMI) patients treated with fibrinolytic therapy compared early and deferred beta
blocker therapy and found no clear evidence of a mortality benefit with early beta
blocker [22,30,31]. In these studies, deferred therapy occurred within 24 hours to up to
six days.

The findings were somewhat similar in the randomized COMMIT/CCS2 trial of almost
46,000 MI patients (93 percent with ST elevation or left bundle branch block), one-half
of whom received fibrinolytic therapy [32]. In this trial, patients were randomly assigned
to placebo or to three 5 mg intravenous boluses of metoprolol tartrate followed by oral
metoprolol extended release (succinate) 200 mg/day for 30 days. There was no overall
mortality benefit from early intravenous beta blocker therapy. However, hemodynamic
stability appeared to be an important determinant of the response to beta blockers.
There was a significant increase in mortality in patients who presented with
hemodynamic compromise that was balanced by a trend toward reduced mortality in
patients who were hemodynamically stable. Importantly, patients with hemodynamic
compromise and who received beta blockers did not go through a period of up-titration
of the drug, raising the possibility that a more careful use of early intravenous beta
blocker may improve outcomes.

Some evidence of benefit of early intravenous administration comes from the following
studies:

●The TIMI-IIB trial randomly assigned 1434 patients to either early intravenous
(IV) therapy (metoprolol tartrate, 15 mg IV given in three equal doses at two-
minute intervals if tolerated, followed by 50 mg orally twice daily for the first day
and 100 mg orally twice daily thereafter) or to delayed oral beta blockade
(metoprolol, 50 mg twice daily on day six and 100 mg twice daily thereafter)
[30].

●Immediate beta blocker therapy may reduce the incidence of intracerebral

hemorrhage [30,33]. This effect was suggested in a review of data from 60,329
patients treated with alteplase in the National Registry of Myocardial Infarction
[33]. Immediate beta blocker use was associated with a lower incidence of
intracerebral hemorrhage (0.67 versus 1 percent for no immediate beta blocker;
odds ratio 0.69, 95% CI 0.57-0.84). This apparent benefit was seen in all age
groups and in both men and women.

●Pooled data from controlled trials involving over 29,000 patients undergoing
early, short-term IV administration of a beta blocker showed a 13 percent
relative risk reduction in acute mortality [34].

Primary PCI — The evidence presented below does not support the routine use of
intravenous beta blocker prior to primary percutaneous coronary intervention (PCI). It
should also be kept in mind that clinical experience has shown that intravenous therapy
has worsened outcomes in patients with hemodynamic instability or evidence of Killip
Class II or III (table 1) heart failure. It must be given cautiously or avoided in these
patients.

Two randomized trials, each with significant limitations, have evaluated the role of
intravenous beta blocker before primary PCI:

●In METOCARD-CNIC, 270 patients with Killip class II or less (table 1) anterior
STEMI were randomly assigned to receive intravenous metoprolol (up to three
5 mg boluses of metoprolol tartrate given two minutes apart) or not before
 reperfusion and all patients received oral metoprolol within 24 hours [35]. The
primary end point of infarct size on magnetic resonance imaging performed five
to seven days was significantly smaller in the group that was treated early (25.6
versus 32.0 grams; p = 0.012). In addition, left ventricular ejection fraction was
higher in the treated group at five to seven days and at six months (adjusted
treatment difference 2.67 percent; p = 0.045 and 3.49 percent; p = 0.025) [36].
There was no difference in the safety end point. Limitations of the study include
lack of a placebo control and exclusion of patients with inferior MI.

●In the EARLY-BAMI trial, 683 patients with STEMI were randomly assigned to
intravenous metoprolol (two sequential 5 mg boluses) or placebo before PCI
[37]. The first bolus was given in the ambulance. The primary end point of
myocardial infarct size (percent of LV), as assessed by cardiac magnetic
resonance imaging at 30 days, was performed in 342 patients. There was no
difference in infarct size between the two groups (15.3 versus 14.9 percent,
respectively). Supporting this finding of no difference was a lack of difference in
the secondary end point of peak and area under the creatinine kinase curve.
Limitations of the study include failure to achieve the necessary sample size for
the primary end point, the possibility that the groups with and without
measurement of the primary end point were not well balanced, and a smaller
than estimated infarct size than predicted, which may have made it harder to
find a true difference. There was no difference in the rate of adverse events
between the two groups.

Observational studies have also not shown convincing evidence of benefit from early
intravenous beta blocker use:

●An apparent benefit from preprocedural intravenous administration of a beta

blocker was also shown in a retrospective analysis from the CADILLAC trial of
2082 patients [38]. At 30 days, patients who had received a preprocedural beta
blocker had a significantly lower mortality than those who had not (1.5 versus
2.8 percent); the lower mortality was limited to patients who had not been
receiving an oral beta blocker before admission. (See "Primary percutaneous
coronary intervention in acute ST elevation myocardial infarction: Determinants
of outcome".)

●The optimal timing of beta blocker therapy was evaluated in a study of patients
enrolled in the TIMI II trial [31]. A subset of 1390 patients who were eligible for
intravenous beta blockade were randomly assigned to 15 mg of IV metoprolol
tartrate (followed by oral metoprolol) or oral metoprolol begun on day six. There
was no significant difference between the two groups in the in-hospital left
 ventricular ejection fraction or in mortality at 6 and 42 days. However, by day
six, the early therapy group had significant reductions in nonfatal reinfarction
(16 versus 31 patients) and recurrent ischemic episodes (107 versus 147
patients).

Patients who do not receive a beta blocker during the first 24 hours because of early
contraindications should be re-evaluated for beta blocker candidacy for subsequent
therapy.

Choice of drug and route of administration — A cardioselective oral beta blocker,

such as metoprolol or atenolol, is preferred in the setting of an acute myocardial
infarction (MI). We use oral metoprolol tartrate 25 to 50 mg every 6 to 12 hours or
atenolol 25 to 50 mg twice daily, initially, titrating upward as needed. Short-acting beta
blockers are preferred early to allow for more rapid adjustment of dose based on the
patient’s blood pressure and heart rate response. Near the time of discharge, we prefer
to switch to longer-acting beta blockers.

For the uncommon patient in whom intravenous therapy may be chosen, such as those
with ongoing ischemia prior to PCI in whom there is no hemodynamic instability
including heart failure, we suggest the following regimens [16] (see 'Primary PCI'
above):

●Intravenous metoprolol tartrate can be given in 5 mg increments by slow

intravenous administration (5 mg over one to two minutes), repeated every five
minutes for a total initial dose of 15 mg (three doses). Patients who tolerate this
regimen should then receive oral therapy with either metoprolol succinate 50
mg daily or metoprolol tartrate 25 mg 2 to 4 times daily beginning 15 to 30 min
after the last intravenous dose.

●Intravenous atenolol can be given in a 5 mg dose followed by another 5 mg

five minutes later. Patients who tolerate this regimen should then receive
maintenance oral therapy with atenolol 50 mg every 12 hours daily beginning
one to two hours after the last intravenous dose. Intravenous atenolol is not
available in the United States or Canada.

●Esmolol (50 mcg/kg per min increasing to a maximum of 200 to 300 mcg/kg
per min), an ultra-short-acting beta blocker, can be given to assess tolerance to
beta blockade in patients with borderline or questionable left ventricular
function.

Bradycardia and hypotension are the most common limitations to achieving the full
dose. In this setting, the rate of administration should be slowed or oral therapy
initiated. However, a rigid "cookbook" regimen should not be used since there is a
variable sympathetic response to acute MI.

Patients with hypertension — Some experts have recommended the use of

intravenous beta blocker therapy for patients with acute MI and hypertension. Due to
our concerns regarding this application of intravenous beta blockade, we prefer
intravenous nitroglycerin, starting at a low dose, for such patients. (See 'Primary PCI'
above.)

Special situations (eg, malignant hypertension or dissecting aortic aneurysm) may

require the judicious use of intravenous beta blockade in such patients.

LONG-TERM THERAPY — While all patients with acute myocardial infarction (MI)
should receive long-term beta blocker therapy, the optimal duration, dose, and agent
are not known. We recommend the use of a long-acting, once daily beta blocker to
improve treatment adherence.

Duration — The optimal duration of beta blocker therapy after MI is not known. We
believe the evidence supports the use of beta blockers in patients with MI for as long
as three years. The evidence supporting a longer duration, or indefinite therapy, is
limited. We suggest doing so in patients with high-risk features at presentation such as
cardiogenic shock, heart failure, or chronic kidney disease. For patients without these
high-risk features, we suggest that practitioners discuss the potential benefits and risks
of continued therapy with patients and have them participate in decision making. (See
'Contraindications' below.)

Although the adjusted incidence rate of hospitalization for acute MI has declined by 4 to
5 percent per year since 1987, approximately 200,000 recurrent episodes of acute MI
occur annually [39]. Whereas ischemic heart disease has become the leading
contributor to the burden of disease as assessed on the basis of disability-adjusted life-
years [40], and survival from acute MI is associated with the increasing incidence of
heart failure in the United States, there exists a sound argument for prolonged,
indefinite beta-blocker therapy post-MI.

We believe it is reasonable to discontinue beta blocker therapy, using a tapering

protocol carried out over a few weeks, in patients with unacceptable side effects, for
whom the financial burden is unacceptable, or in those for whom the use of multiple
medications is problematic (polypharmacy). There are no known life-threatening side
effects (such as proarrhythmia or malignancy) of long-term beta blocker therapy [41].

Many patients have been continued on this therapy indefinitely based on a 1999 meta-
analysis of over 50,000 patients that showed a 23 percent reduction in death at a mean
follow-up of 1.4 years [23]. In addition to the relatively short duration of follow-up,
application of the conclusions of this meta-analysis is limited as reperfusion and
medical (aspirin and statin) therapies were underutilized routinely. The findings in this
meta-analysis were supported by a large observational study published in 1998 [21].

A more contemporary evaluation of the potential benefit from long-term beta blocker
use was made in a 2012 observational study of over 14,000 patients with known prior
MI enrolled in the international REACH registry [42]. Patients were enrolled in 2003 and
2004 and followed prospectively for up to four years. The primary outcome was a
composite of cardiovascular death, nonfatal MI, or nonfatal stroke. Propensity score
matching identified 3599 pairs of patients with and without beta blocker use. Aspirin
and statin use (each) was approximately 75 percent. After a median follow-up of 44
months, there was a trend toward a lower incidence of the primary outcome with beta
blocker therapy (16.9 versus 18.6 percent, respectively; hazard ratio 0.90, 95% CI
0.79-1.03). However, little difference was seen in the event rates in the beta blocker
and no beta blocker groups as early as two years.

A 2013 observational study evaluated outcomes in 5628 patients with ST-elevation MI

(STEMI) treated with primary percutaneous coronary intervention. During a median
follow-up of nearly four years, mortality rates did not differ between patients with and
without beta blocker therapy (5.2 versus 6.2 percent) [25]. The absence of a significant
difference persisted after multivariate and propensity score matching. However,
subgroup analyses revealed that beta blocker treatment was associated with a
significantly lower mortality for only high-risk patients, such as those with heart failure.

The role of long-term beta blocker therapy in patients with significant left ventricular
systolic dysfunction is discussed separately. (See "Use of beta blockers in heart failure
with reduced ejection fraction", section on 'Dosing' and "Use of beta blockers in heart
failure with reduced ejection fraction".)

Dose — The optimal long-term dose for each beta blocker is not known. Our approach
is to attempt to prescribe doses used in randomized trials.

While it makes sense to recommend the doses used in the randomized trials, that
approach has not been adopted widely by the medical community. The practice of
using a lower dose than used in the trials is supported by a 2015 multicenter registry
(OBTAIN) study that evaluated the relationship between dose and survival in 6682
acute MI survivors who were discharged on a beta blocker [43]. Discharge beta blocker
dose was compared with target doses used in the randomized trials, grouped as >0 to
12.5 percent, 12.5 to 25 percent, >25 to 50 percent, and >50 percent of target dose.
The following was noted after 2.1 years median follow-up:
 ●91.5 percent of all patients were discharged on a beta blocker, with a mean
dose 38.1 percent of the target dose. Metoprolol and carvedilol accounted for
92 percent of the drugs used, with target doses of 200 mg/day and 50 mg per
day, respectively.

●Lower mortality was observed with all doses compared with non-beta blocker
therapy.

●The primary end point of the study was mortality at two years. Compared with
the >50 percent dose, the adjusted hazard ratios for the mortality for the 0 to
12.5, 12.5 to 25, and 25 percent groups were 0.86, 0.80, and 0.96, respectively.
None of these were statistically significant.

This study raises the possibility that doses lower than those used in clinical trials may
lead to similar or better outcomes. However, the study has significant limitations and
we recommend doses uses in randomized trials.

Agent — For long-term administration, we believe that the benefit from beta blockers
(table 2) is a class effect and that agents without intrinsic sympathomimetic activity
(ISA) are preferred [44-46]. In a 1999 meta-analysis of randomized controlled trials,
there was no significant difference in benefit with cardioselective compared to
nonselective drugs, but there was an almost significant trend toward less benefit with
drugs that have ISA [23].

We start with a beta-1-selective agent in most patients. Usual initial doses are
metoprolol tartrate (immediate release preparation) 25 to 50 mg two to four times daily
or metoprolol succinate (extended release preparation) 50 or 100 mg daily or atenolol
50 to 100 mg divided twice daily. When possible, we use the longer-acting preparation.
For patients in whom there is a concern for intolerance to these doses, lower initial
doses should be used; in this setting, up-titration should occur as promptly as possible.

Patients with heart failure with reduced ejection fraction (HFrEF) should be treated
long-term with carvedilol, extended-release preparation metoprolol succinate, or
bisoprolol. (See "Pharmacologic therapy of heart failure with reduced ejection fraction",
section on 'Beta blocker' and "Use of beta blockers in heart failure with reduced
ejection fraction".)

Heart rate goal — We suggest reducing the heart rate below 70 beats per minute
while maintaining a systolic pressure above 90 mmHg, based on a small amount of
published evidence and our clinical experience.
An inverse relationship between short-term and long-term mortality and the degree of
heart rate reduction with beta blockade after MI was suggested in the 1980s [47]. This
hypothesis was confirmed in a 2007 meta-regression analysis of 17 trials including
nearly 31,000 MI patients who were placed on either a beta blocker (14 trials) or a rate
slowing calcium channel blocker (three trials) [48]. There was a statistically significant
and progressive reduction in the odds ratio for all-cause and cardiac death and non-
fatal MI as the resting heart rate was slowed from 5 to 15 beats per minute compared
to baseline. However, the optimal degree of heart rate lowering is unknown.

CONTRAINDICATIONS

Absolute contraindications — Potential absolute contraindications to the immediate

use of beta blocker therapy include the following groups:

●Hemodynamically compromised individuals, including those with hypotension

with or without shock [44,45].

●Patients with active bronchospasm, heart block greater than first degree
(unless the patient has a permanent pacemaker), those with first degree heart
block and a PR interval >0.30 seconds, or severe bradycardia. The rate at
which a patient is labelled as having severe bradycardia is somewhat age
dependent, as heart rate tends to decrease normally with age. While there is
little evidence upon which to guide recommendations for the use of beta
blockers in patients with bradycardia, we do not start such therapy in patients
with a heart rate <40 beats per minute (BPM). Above 40 BPM, our threshold for
starting beta blockers is lower in younger patients. Some of our experts use a
higher threshold than 40 BPM.

●Patients with overt heart failure, including pulmonary edema. However, there
is a strong indication for carefully initiated oral beta blocker therapy (beginning
at very low doses) in such patients whose heart failure has been brought under
control prior to discharge. (See "Use of beta blockers in heart failure with
reduced ejection fraction", section on 'Initiation of therapy'.)

The role of beta blocker therapy in patients with myocardial infarction (MI) precipitated
by cocaine use is controversial. (See "Cocaine: Acute intoxication".)

Patients with comorbidities — A survival benefit from beta blockade is seen in

patients with relative or potential contraindications to such therapy such as chronic
obstructive pulmonary disease (COPD)/asthma, reduced left ventricular (LV) ejection
fraction, treated heart failure, diabetes mellitus, and peripheral artery disease [21,49-
56].
COPD/asthma — Beta blockers are safe and effective in MI patients with mild to
moderate pulmonary disease (table 3) as illustrated by the following data from
observational studies:

●In a study of 54,962 MI patients over the age of 65 years who had no
contraindications to beta blocker therapy, beta blockers were associated with a
lower one-year mortality in patients with COPD or asthma who were not on beta
agonist therapy (adjusted relative risk 0.85 compared to no beta blockers); the
lower mortality was similar to that seen in patients without COPD or asthma
[52]. In contrast, beta blockers had no difference in survival in patients who
were using a beta agonist or who had severe COPD or asthma.

●In a review of over 200,000 MI patients from the Cooperative Cardiovascular

Project, survival among patients with COPD was significantly higher in those
treated with a beta blocker (83 versus 72 percent without a beta blocker) at two
years (figure 2) [21].

●In a cohort study of 1063 patients with mild or moderate COPD (table 3) who
sustained a first MI, mortality was lower in those who started or were previously
taking a beta blocker (adjusted hazard ratios 0.50, 95% CI 0.36-0.69 and 0.59,
95% CI 0.44-0.79, respectively) during nearly three years of follow-up [57].

Diabetes mellitus — Concern about the possibility of masking hypoglycemic

symptoms or worsening glycemic control has made some physicians reluctant to
prescribe beta blockers to patients with diabetes during an acute MI. However, these
concerns have been overstated, and analysis of outcomes of diabetic subgroups in
several postinfarction beta blocker trials documents an overall benefit from the use of
beta blockers that is at least equivalent to and may be greater than that seen in
patients without diabetes. (See "Treatment of acute myocardial infarction in diabetes
mellitus", section on 'Beta blockers'.)

Peripheral artery disease — Although there has been a concern involving the use of
beta blockers in patients with intermittent claudication, there appears to be no adverse
effect of beta-1 selective blockers on claudication symptoms [58-60]. The use of beta
blockers in patients with peripheral artery disease, including abdominal aortic
aneurysm, is discussed elsewhere. (See "Management of claudication".)

Patients treated with antiarrhythmic drugs — Beta blockers are effective in patients
treated with antiarrhythmic drugs (figure 3 and figure 4) [34,41,61]. This was illustrated
in a pooled analysis of patients in the CAMIAT and EMIAT trials of amiodarone in acute
MI [61]. The relative risks for all-cause mortality, cardiac death, arrhythmic deaths, and
resuscitated cardiac arrest were lower for patients receiving beta blockers along with
amiodarone than for those without a beta blocker, with or without amiodarone. This
interaction was significant for cardiac death and for arrhythmic death or resuscitated
cardiac arrest (relative risk 0.59 and 0.39) (figure 5A-B) [61]. Antiarrhythmic drugs other
than amiodarone have not been similarly studied. (See "Role of antiarrhythmic drugs
for ventricular arrhythmias in patients with a prior myocardial infarction" and
"Prophylaxis against ventricular arrhythmias during and after acute myocardial
infarction".)

RECOMMENDATIONS OF OTHERS — Our approach to the use of beta blockers in

patients with acute myocardial infarction (MI) is similar to that made in the 2011
guideline on secondary prevention published by the American Heart
Association/American College of Cardiology [62] and the 2015 European Society of
Cardiology guidelines for the management of acute coronary syndromes in patients
presenting without persistent ST-segment elevation [63].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored

guidelines from selected countries and regions around the world are provided
separately. (See "Society guideline links: Non-ST elevation acute coronary syndromes
(non-ST elevation myocardial infarction)" and "Society guideline links: ST elevation
myocardial infarction (STEMI)".)

SUMMARY AND RECOMMENDATIONS

●Beta blockers should be given to all myocardial infarction (MI) patients with
current or prior heart failure (HF) and a left ventricular ejection fraction ≤40
percent. (See 'LV dysfunction/heart failure' above.)

For all patients who have sustained an acute MI without HF and preserved left
ventricular systolic function and who have been treated with standard-of-care
risk factor interventions, as well as dual antiplatelet therapy, we suggest
treatment with an oral beta blocker (Grade 2C). (See 'Indications' above.)

●For all patients with acute MI, we recommend initiation of oral beta blockers
within the first 24 hours, as long as no contraindications are present. (Grade
1B). (See 'Indications' above and 'Absolute contraindications' above.)

Patients who do not receive a beta blocker during the first 24 hours because of
early contraindications should be reevaluated for beta blocker candidacy. (See
'Primary PCI' above.)
●The optimal duration of beta blocker therapy is not known. We treat most
patients for a minimum of three years. In high risk patients, such as those who
present with cardiogenic shock, heart failure, or chronic kidney disease, we
treat for longer than three years. (See 'Long-term therapy' above.)

●We attempt to get the heart rate below 70 beats per minute while maintaining
a systolic pressure above 90 mmHg. (See 'Heart rate goal' above.)

●Absolute contraindications to the initiation of beta blocker therapy include

cardiogenic shock, active bronchospasm, severe bradycardia or heart block
greater than first degree (unless the patient has a permanent pacemaker), and
patients with overt heart failure. Patients with treated heart failure or
bronchospastic lung disease, peripheral artery disease, or diabetes mellitus
should receive beta blocker therapy; however, these individuals should be
monitored for the development of adverse side effects. (See 'Contraindications'
above.)