New data...

Intravenous beta-blockers in patients with ST-elevation myocardial infarction treated with primary PCI

This study supports current guideline recommendations for very selective intravenous beta-blocker administration in patients with STEMI. The authors state that intravenous beta-blocker use ranges from 2% to 40% in Swedish hospitals, suggesting an opportunity for quality improvement by standardising therapeutic protocols across hospitals to be more consistent with guideline-directed medical therapy. This report should prompt hospitals and STEMI teams to review their use of intravenous beta-blockers in patients with STEMI. The best and only proven strategy to decrease infarct size and improve left ventricular function in patients with STEMI is decreasing time-to-treatment with reperfusion therapy and minimising the early risk for hypotension, heart failure, and cardiogenic shock.

Article Intravenous beta-blocker therapy in ST-Segment Elevation Myo...

I would simply refer to the prevailing guidelines:

NSTEMI: doi:10.1093/eurheartj/ehv320

Beta-blockers competitively inhibit the myocardial effects of circulating

catecholamines and reduce myocardial oxygen consumption

by lowering heart rate, blood pressure and myocardial contractility.

The evidence for the beneficial effects of beta-blockers in

NSTE-ACS is derived from a meta-analysis of 27 early studies showing

that beta-blocker treatment was associated with a significant

13% relative risk reduction (RRR) of mortality in the first week following

MI.118 In addition, a later meta-analysis comprising 73 396 patients

with ACS showed an 8% RRR (P . 0.04) for in-hospital

mortality associated with beta-blockade, with no increase in cardiogenic

shock.119 A registry study of 21 822 NSTEMI patients found

that in patients at risk of developing cardiogenic shock (i.e. age

.70 years, heart rate .110 beats/min, systolic blood pressure

,120 mmHg) the observed shock or death rate was significantly increased

in patients receiving beta-blockers within 24 h of hospital

admission.120 Therefore early administration of beta-blockers

should be avoided in these patients if the ventricular function is unknown.

Beta-blockers should not be administered in patients with

symptoms possibly related to coronary vasospasm or cocaine use,

as they might favour spasm by leaving alpha-mediated vasoconstriction

unopposed by beta-mediated vasodilation.

STEMI: https://doi.org/10.1093/eurheartj/ehs215

The benefit of long-term treatment with beta-blockers after STEMI

is well established, although mostly from trials pre-dating the

advent of modern reperfusion therapy and pharmacotherapy.

The role of routine early i.v. administration, on the other hand,

is less firmly established. Oral administration of beta-blockers

appears to be associated with benefit, but high, early i.v. dosage

was associated with an early hazard and increased mortality in

the large COMMIT trial.266 Thus, early i.v. use of beta-blockers is

contraindicated in patients with clinical signs of hypotension or

congestive heart failure. Early use may be associated with a

modest benefit in low-risk, haemodynamically stable patients. In

most patients, however, it is prudent to wait for the patient to stabilize

before starting a beta-blocker and to use oral, rather than i.v.,

administration. In contemporary trials utilizing primary PCI, betablockers

have not been investigated, although it is not unreasonable

to extrapolate their benefit to this setting.

In conclusion, modest additional benefits. Careful evaluation of this therapy seems mandatory. 

Best Regards,

Thierry

Thanks a lot Thierry for your answer!

I am completely agree with you.

We say beta-blocker, but we mean metoprolol. Because we do not have any data about bisoprolol, carvedilol or atenolol, according evidence based medicine in patients with AMI. 

And my question: What about another β-blockers in patients with AMI? steel open!

This doen't matter. What matters is the myocardial damage, the recovery of damaged cells and the steering of the compensatory hypertrophic response of remaining living cells. Beta-blockers (in particular metoprolol, carvedilol) are the best documented drugs with carvedilol being better. 

By the same token, ivabradine works in HF and decreased function, but not in ischaemic heart disease. I have a lecture kit on this made with the help of Carl Swedberg. 

Thierry

I want to draw attention to the study of atenolol in patients with MI - ISIS-I (Lancet 1988).

Atenolol was compared with placebo. In atenolol group (n = 8037) intravenous atenolol (5 mg twice with an interval of 10 min) the patients started no later than 12 h from the onset of myocardial infarction. After this, atenolol was prescribed per os at a dose of 100 mg in 1-2 divided doses. In the control group (n = 7990), standard MI therapy was performed using placebo.

To date, from the point of view of evidence-based medicine, these data are not valid.

The data did not indicate any substantial contribution from mechanisms such as limitation of infarct size or prevention of reinfarction or cardiac arrest.

It may be worth looking at the recent study done with metoprolol in Spain. They used metoprolol upfront prior to reperfusion in STEMI, and then analyzed the data according to time to reperfusion and published in J Am Coll Cardiol. In reality it seems that the benefit is greatest when the metoprolol is given earlier before reperfusion as it reduces infarct size when ischemia is still ongoing, if given shortly before reperfusion or after reperfusion the benefits are modest or absent.

Fortunately most of the patients now are reperfused immediately or very soon, so there may be little space of pre-reperfusion metoprolol. Perhaps it can be useful for those patients who are not successfully reperfused - but this has not been tested and those would be at risk for hypotension, heart failure and shock.

Good research. My congratulations.

It's obvious that the sooner we start therapy, the better result. Less infarct size. This also applies to statins.

As the results of your study, metoprolol should be given to patients in the ambulance. Then there will be the best result for limiting zone of myocardial necrosis.

 All b-blockers have the same mechanism of action, the main differences are in pharmacokinetics: lipid- or water-solubility, onset and duration of action, biotransformation and route of elimination. Metoprolol is preferred in AMI because it's cardiac selective, lipid-soluble,  has relatively fast onset of action and duration of action. Carvedilol is not really best choice because it provides additional a-blocking activity. Bisoprolol is better. Oral route of administration is more save. In case of i/v injection bioavailability will be 100% and it result in hypotension or suppressed cardiac contractility. But b-blocker should be used if there's no contraindications. Prescription of of other b-blocker depends on pharmacokinetic and pharmacodynamic features. 

Thanks a lot Olha!

Welkome to RG family.

I completelly agree with you. But if we talk about evidence baset medicine it is little known about b-blokers in AMI. We have RCT with mrtoprolol. What about other? 

Last time treatments patients with AMI changed. For example: DAT, TAT, high doses of statins, mechanical reperfusion...  The class effect does not always work.

Benefit of betablocker in MI are reduction of infarct size and prevention of arrhythmia and sudden cardiac death. But benefits are much more established in prethrombolytic and pre PCI era. Data are much strong with meteprolol.However atenolol,propranolol,timolol and intravenous esmolol may be also beneficial. Patient with left ventricular dysfunction probably will get long term benefit with bisoprolol, nevibolol and carvedilol but how much they will reduce the infarct size is not well established.. 

https://www.slideshare.net/mobile/DrSatyamRajvanshi/beta-blockers-in-acute-mi

OK. Let us talk about propranolol.

The BHAT trial followed the Norwegian Trial and was halted early due to a significant mortality reduction with BB treatment. The BHAT trial randomized 3,837 patients 5-21 days (not first 24 h) after acute MI to propranolol, a non-selective BB, or placebo (AMI and placebo?) with a mean follow-up of 27 months. Patients with bradycardia, CHF and prior BB treatment were excluded. Total mortality was reduced by 25%, sudden death by 28% and arteriosclerotic heart disease by 27%. The survival curves diverged for the first year, then became parallel. The benefits of propranolol were found to be similar in all risk groups. 

A sub-analysis of the BHAT database by Viscoli et al.: The authors found that while propranolol therapy conferred an improvement in mortality of 43% among high risk patients, there was no evidence of long term benefit in the low risk population, calculated to be approximately 88% of the cohort.

The findings of BHAT were further evaluated in a posthoc analysis by Georghiade et al.: The authors concluded that the beneficial effects of propranolol were limited to the Q-wave MI population.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394111/pdf/CCR-8-77.pdf

In continue to talk about propranolol in AMI patients.

The discovery of propranolol in 1964 and its introducing to the clinical practice has been essential for the progress in the diagnostics and therapy of cardiovascular diseases.

Last time we use propranolol in AMI patients 25 years ago! Dose taken four times per day.

This is inconvenient from the position of polypharmacy. The recommended total dose per day is 180–240 mg. 

At that time it was an excellent drug. Today, we have in the arsenal of modern beta-blockers.

Today, in my opinion propranolol can be used as a short beta blocker.

The current protocol of treatment of AMI patients implies the usage of b1-selective blockers, like metoprolol, to produce the best therapeutic effect. It also helps to decrease episodes of ventricular arrhythmia, such as ventricular extrasystoles, during AMI and control the ventricular rate. This drug has a well-established anti-ischemic effect by decreasing the inotropic function of the heart and thereby, the myocardial oxygen demand. In addition, the anti-inflammatory effects of this drug can play a role in reducing infarct size and improving cardiac function in patients with AMI.

Nevibolol is an important drug used for treatment of hypertension, both systolic and diastolic heart failure. Though data are much strong with meteprolol in regard to reduction of infarct size,some human study is needed with nevibolol to evaluate it's effect in reducing infarct size. Animal study in mice has shown promise in reducing scar size after AMI...

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0098179

Beta-Blockers have been used extensively in the last 40 y after AMI as part of therapy and in secondary prevention. The evidence for “routine” therapy with beta-blocker use post AMI rests largely on results of trials conducted over 25 years ago.

Based on the latest ACC/AHA guidelines - class IIa.

Question: Class effect of beta-blockers?

What about bisoprolol?

There are some indication that beneficial effect of beta blocker after MI may be because of class effect. Data in human is very limited with bisoprolol in regards to reduction of infarct size. One study in rat showed beneficial effect of bisoprolol in small MI but beneficial effect is not seen in large Mi.. Thanks 

http://www.nature.com/articles/srep13692

Interesting data published in Am J Cardiol. 2015.

Of the 1741 patients discharged on beta-blocker therapy, 70.7% were administered metoprolol, 19.5% carvedilol (including CoregCR), 3.5% atenolol, 0.3% propranolol, 5.2% bisoprolol, and 0.86% received other beta-blockers.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939010/pdf/nihms216638.pdf

Interesting data from Taiwan. The study identified patients with first ST-elevation MI for the period of 2003 to 2010 from the National Health Insurance claims database. Among the 16836 patients, 7591 were prescribed carvedilol, 5934 bisoprolol, and 3311 propranolol. After accounting for baseline differences, patients treated with bisoprolol (HR 0.87, 95% CI 0.72–1.05, p = 0.14) or propranolol (HR 1.07, 95% CI 0.84–1.36, p = 0.58) had a similar risk of all-cause death in comparison with carvedilol. No significant differences were observed among three beta-blocker groups with regard to the risks of cardiovascular death and recurrence of MI.

https://www.nature.com/articles/srep13692

There is an interesting data in acute MI with LV dysfunction with regards to betablockers. Nevibolol, meteprolol and carvedilol were compared. Nevibolol showed better cardiovascular event rate compared to meteprolol. Carvedilol and nevibolol showed similar out come. Nevibolol has got some unique benefit among the betablockers like vasodilator property.. Some large study is needed with nevibolol in acute MI... to evaluate it's role specially in acute MI with LV dysfunction.. What is your opinion Sergey.. In this regard? Thanks 

https://www.ncbi.nlm.nih.gov/pubmed/27164841

Dear Biswajit,

1 - if we talk about evidence based medicine - nebivolol is not indicated for treatment AMI.

2 - but for science it is justified.

Right now I am not recommended to use nebivolol in those patients.

Of course we need RCT.

The current 2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromessuggests that it is reasonable to continue beta-blocker therapy in patients with normal left ventricular (LV) function with ACS without ST-segment elevation (Class IIa, Level of Evidence C) (Table 2). The 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction lends a Class I, Level of Evidence B recommendation that beta-blockers should be continued during and after hospitalization for all patients with ST-segment elevation MI and no contraindications. However, these guidelines also comment that long-term duration of routine beta-blocker therapy in patients without HF or hypertension has not been prospectively addressed and refer to the AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2011 Update, recommending 3 years of beta-blocker therapy in this subset (Class I, Level of Evidence B). Continuation of beta-blockers beyond 3 years in these patients is considered reasonable (Class IIa, Level of Evidence B). These guidelines are largely based on evidence pre-dating contemporary medical and reperfusion strategies. The 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation recommend only long-term management with beta-blockers post-MI in those patients with LV ejection fraction (LVEF) ≤ 40%, stating that contemporary randomized trials of beta-blocker therapy have not been conducted in patients after ACS without ST-segment elevation with normal LV function. From article How Long Should We Continue Beta-Blockers After MI?

Current data suggest that long term betablocker therapy are beneficial in post MI patient with reduced left ventricular systolic dysfunction. Role of long term beta blocker therapy in post MI patient with normal left ventricular systolic function is not clear.  In post MI patient with normal left ventricular systolic function who have coronary artery lession which is non revascularisable, who have scar in myocardium or gross LVH.. might get long term benefit of betablocker in reducing SCD.. 

http://www.acc.org/latest-in-cardiology/articles/2017/01/20/09/36/how-long-should-we-continue-beta-blockers-after-mi

In continue...

Which patients, then, should receive beta-blockers during an index hospitalization for ACS? Patients at low risk for cardiogenic shock should be started on a beta-blocker in-hospital to reduce the risk of reinfarction and angina; this is applicable for most patients with an MI. Extrapolating from pre-reperfusion-era trials, patients presenting late with large infarct size and perhaps without revascularization may have the greatest benefit from continuation of oral beta-blockers, including potential reduction in mortality and sudden death. These are also patients who will have reduced LVEF, where beta-blockers remain the standard of care. By K. Bockstall and S. Bangalore.

New data...

Intravenous beta-blockers in patients with ST-elevation myocardial infarction treated with primary PCI

This study supports current guideline recommendations for very selective intravenous beta-blocker administration in patients with STEMI. The authors state that intravenous beta-blocker use ranges from 2% to 40% in Swedish hospitals, suggesting an opportunity for quality improvement by standardising therapeutic protocols across hospitals to be more consistent with guideline-directed medical therapy. This report should prompt hospitals and STEMI teams to review their use of intravenous beta-blockers in patients with STEMI. The best and only proven strategy to decrease infarct size and improve left ventricular function in patients with STEMI is decreasing time-to-treatment with reperfusion therapy and minimising the early risk for hypotension, heart failure, and cardiogenic shock.

Article Intravenous beta-blocker therapy in ST-Segment Elevation Myo...

Dear Biswajit Majumderin,

the continuation of the discussion on the duration of admission of the BAB ...

I fully agree with you that patients with high cardiovascular risk should use BAB as long as possible. Unfortunately, the recommendations do not always give an answer to this question. And here rely on the opinion of the doctor, taking into account the individual approach to each patient.

Break news: Blockers May Raise Mortality in People With Diabetes

Use of beta-blockers may be associated with an increased mortality risk in patients with diabetes, particularly among those who have coronary heart disease (CHD), new research suggests.

https://www.medscape.com/viewarticle/894878?nlid=121699_3801&src=WNL_mdplsnews_180406_mscpedit_card&uac=7532HN&spon=2&impID=1600983&faf=1#vp_1

Hi Sergey,, very interesting data. Beta blockers reduce cardiovascular mortality in post MI LV dysfunction nondiabetic patient that is well proven. But it 'S role in stable coronary artery disease in diabetes and nondiabetic patients was debatable. But this study showed increased mortality in diabetes is quite interesting. What is the mechanism of increased mortality in diabetes wheather prevention of manifestation of hypoglycemia or interfaring with diabetic autonomic neuropathy ? Can you enlighten in this aspect? Thanks

Dear Majumder

The new observations related to the adverse effects of beta blockers in post MI diabetic patients has come as a surprise. It may not be advisable to prescribe beta blockers to post MI diabetic patients with preserved LV function. In our day to day practice, it is not uncommon to prescribe beta blockers to diabetic post MI patients for secondary prevention even after they are revascularised irrespective of LV function.This should be discouraged based on the current evidence. The reason for the deleterious effects of beta blockers could be related to weight gain, adverse effects on lipids, higher central aortic pressure and worsening of glycemic control or the problems related to hypoglycemia. It is worthwhile trying to find out if there are differences between the various beta blockers. Is it possible that some of them were on Atenolol? Also, one should specifically look at the group who received Carvedilo.

COMMENT: Beta-Blockade After MI: No Practice Should Be Set in Stone

A patient presented soon after having chest pain. The electrocardiogram (ECG) showed an ST-elevation myocardial infarction (STEMI). The day after acute percutaneous coronary intervention (PCI), cardiac enzymes met the definition of myocardial infarction (MI) but the echocardiogram showed a normal left ventricular ejection fraction (LVEF).

Should this person be treated with a β-blocker?

Dear Sergey,

This patient obviously has STEMI with preserved LVEF who has undergone successful PCI. In post MI patients who have undergone revascularisation and with preserved LV function, normal end systolic volumes, absence of any residual ischemia and with no arrhythmias, there is no compelling indication for beta blocker. If the resting heart rate is high, I may consider beta blocker in your patient though it is not based on any trial data. The beneficial role in secondary prophylaxis is questionable.

Post post MI patients with LV systolic dysfunction, residual myocardial ischemia and or electrical instability certainly require beta blocker. In heart failure, one among the 3 beta blockers - Metoprolol, Bisoprolol or Carvedilol - can be used.

Beta blockers along with ACE inhibitors or ARBs should be preferred in post MI patients with hypertension.

My question is contravershal!

The fast-thinking answer is…yes, of course. High-level medical evidence has shown that β-blockers reduce the rate of death after MI. European and North American guidelines give β-blockers a class I indication. Regulators consider use of these drugs after MI as a marker of quality care.

Please see:

https://www.medscape.com/viewarticle/901940?src=wnl_edit_tpal&uac=7532HN&impID=1739393&faf=1

Thank you. Excellent review and meta analysis on beta blockers in post MI patients in the current era. I also feel that beta blockers may not have any beneficial role in the above patient.

Thanks George for your answer!

Perhaps these patients need beta-blockers, but only in an acute period. But how long to appoint is another matter ...

Here at RG today appeared another article ...

Routine beta-blocker administration following acute myocardial

infarction: why still an unsolved issue?