Unstable angina non ST elevation myocardial infarction beta blockers

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editors-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Varun Kumar, M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S.; Smita Kohli, M.D.; Neil Gheewala, M.D. [3]

Overview

In unstable angina/NSTEMI, the primary benefits of beta blockers are due to the inhibition of beta-1 adrenergic receptors, which results in a decrease in cardiac work and myocardial oxygen demand. Slowing of the heart rate also has a favorable effect, acting not only to reduce myocardial oxygen demand (MVO2) but also to increase the duration of diastole and diastolic pressure-time, a determinant of forward coronary flow and collateral flow.[1]

Indications

In the absence of contraindications (especially hypotension, heart failure and hemodyanamic instability), beta blockers should be initiated either orally or intravenously within first 24 hours.

Contraindications

Patients with marked first-degree AV block (i.e., ECG PR interval greater than 0.24 s), any form of second- or third-degree AV block in the absence of a functioning implanted pacemaker, a history of asthma, severe LV dysfunction or HF (e.g., rales or S3 gallop) or at high risk for shock (see below) should not receive beta blockers on an acute basis.

Clinical Trial Data

Two recent studies (GUSTO-I and COMMIT) have revealed that early aggressive beta blockade poses a substantial net hazard in hemodynamically unstable patients and should be avoided.

In the COMMIT study [2], the utility of early intravenous followed by oral beta blocker (metoprolol) was tested in 45,852 patients with MI (93% had STEMI, 7% had NSTEMI) which showed that neither the composite of death, reinfarction, or cardiac arrest nor death alone was reduced for up to 28 d in the hospital. Overall, a modest reduction in reinfarction and ventricular fibrillation (which was seen after day 1) was counterbalanced by an increase in cardiogenic shock, which occurred early (first day) and primarily in those who were hemodynamically compromised or in HF or who were stable but at high risk of development of shock. Risk factors for shock were older age, female sex, time delay, higher Killip class, lower blood pressure, previous hypertension, higher heart rate, and ECG abnormality.

In GUSTO-I retrospective analyses[3], the administration of intravenous atenolol combined with late oral administration was associated with higher mortality than late oral administration alone. The authors concluded that late oral administration of atenolol might be sufficient and may offer just as good of outcomes as that coupled with early IV administration. Overall, the rationale for beta-blocker use in all forms of CAD, including unstable angina, is generally favorable, with the exception of initial heart failure.

2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes (DO NOT EDIT) [4]

Class I
"1. Oral beta-blocker therapy should be initiated within the first 24 hours in patients who do not have any of the following: 1) signs of HF, 2) evidence of low-output state, 3) increased risk for cardiogenic shock, or 4) other contraindications to beta blockade (e.g., PR interval >0.24 second, second- or third-degree heart block without a cardiac pacemaker, active asthma, or reactive airway disease). (Level of Evidence: A)"
"2. In patients with concomitant NSTE-ACS, stabilized HF, and reduced systolic function, it is recommended to continue beta-blocker therapy with 1 of the 3 drugs proven to reduce mortality in patients with HF: sustained-release metoprolol succinate, carvedilol, or bisoprolol. (Level of Evidence: C)"
"3. Patients with documented contraindications to beta blockers in the first 24 hours of NSTE-ACS should be re-evaluated to determine their subsequent eligibility. (Level of Evidence: C)"
Class III
"1. Administration of intravenous beta blockers is potentially harmful in patients with NSTE-ACS who have risk factors for shock. (Level of Evidence: B)"
Class IIa
"1. It is reasonable to continue beta-blocker therapy in patients with normal LV function with NSTEACS. (Level of Evidence: C)"

2011 ACCF/AHA Focused Update Incorporated Into the ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non -ST-Elevation Myocardial Infarction (DO NOT EDIT)[5][1]

Beta Blockers (DO NOT EDIT)[5][1]

Class I
"1. Oral beta blocker therapy should be initiated within the first 24 h for patients who do not have 1 or more of the following: a- Signs of HF, b- Evidence of a low output state, c- Increased risk for cardiogenic shock, or d- Other relative contraindications to beta blockade (PR interval >0.24 sec, second or third degree heart block, active asthma, or reactive airway disease). (Level of Evidence: B)"
Class III
"1. It may be harmful to administer intravenous beta blockers to Unstable angina / NSTEMI patients who have contraindications to beta blockade, signs of HF or low output state, or other risk factors for cardiogenic shock. (Level of Evidence: A)"
Class IIa
"1. It is reasonable to administer intravenous (IV) beta blockers at the time of presentation for hypertension to Unstable angina / NSTEMI patients who do not have 1 or more of the following: a- Signs of HF, b- Evidence of a low output state, c- Increased risk for cardiogenic shock, d- Other relative contraindications to beta blockade (PR interval >0.24 s, second or third degree heart block, active asthma, or reactive airway disease). (Level of Evidence: B)"

References

  1. 1.0 1.1 1.2 Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE, Chavey WE, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED, Theroux P, Wenger NK, Wright RS, Smith SC, Jacobs AK, Adams CD, Anderson JL, Antman EM, Halperin JL, Hunt SA, Krumholz HM, Kushner FG, Lytle BW, Nishimura R, Ornato JP, Page RL, Riegel B (2007). "ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-Elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine". Journal of the American College of Cardiology. 50 (7): e1–e157. doi:10.1016/j.jacc.2007.02.013. PMID 17692738. Retrieved 2011-04-11. Unknown parameter |month= ignored (help)
  2. Chen ZM, Pan HC, Chen YP, Peto R, Collins R, Jiang LX, Xie JX, Liu LS (2005). "Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial". Lancet. 366 (9497): 1622–32. doi:10.1016/S0140-6736(05)67661-1. PMID 16271643. Retrieved 2011-04-11. Unknown parameter |month= ignored (help)
  3. Pfisterer M, Cox JL, Granger CB, Brener SJ, Naylor CD, Califf RM, van de Werf F, Stebbins AL, Lee KL, Topol EJ, Armstrong PW (1998). "Atenolol use and clinical outcomes after thrombolysis for acute myocardial infarction: the GUSTO-I experience. Global Utilization of Streptokinase and TPA (alteplase) for Occluded Coronary Arteries". Journal of the American College of Cardiology. 32 (3): 634–40. PMID 9741504. Retrieved 2011-04-11. Unknown parameter |month= ignored (help)
  4. Ezra A. Amsterdam, MD, FACC; Nanette K. Wenger, MD et al.2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. JACC. September 2014 (ahead of print)
  5. 5.0 5.1 Wright RS, Anderson JL, Adams CD, Bridges CR, Casey DE, Ettinger SM; et al. (2011). "2011 ACCF/AHA focused update incorporated into the ACC/AHA 2007 Guidelines for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial Infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the American Academy of Family Physicians, Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons". J Am Coll Cardiol. 57 (19): e215–367. doi:10.1016/j.jacc.2011.02.011. PMID 21545940.


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