Clinical:Beta Blockers for Acute Myocardial Infarction

Beta-adrenergic receptor blocking agents (beta-blockers) are drugs with multiple actions on the heart. Blockade of beta-1 receptors results in slowing of heart rate, reduction in myocardial contractility, and lowering of systemic blood pressure. In the context of acute myocardial infarction (AMI), which represents a state of reduced oxygen supply to the affected portion of the heart, these effects may be beneficial as they result in reduced myocardial workload and oxygen demand. Furthermore, beta-blockers may reduce the risk of ventricular arrhythmias, which are an important cause of death following AMI.

Beta-Blockers

Several studies have assessed the value of beta-blockers in patients with ST-segment elevation MI (STEMI), although they have varied in terms of the other treatment provided to the enrolled patients and the type, dose, and route of administration of the beta-blocker.^[1] The International Studies of Infarct Survival-1 (ISIS-1) study compared treatment with the beta-blocker atenolol (intravenous followed by oral) with placebo in patients within 12 hours of presentation.^[2] Atenolol treatment was associated with lower mortality over 7 days (15% relative reduction, 0.6% absolute reduction, p=0.05). The Metoprolol in Acute Myocardial Infarction (MIAMI) trial compared the beta-blocker metoprolol (intravenous followed by oral) with placebo, and found reductions in 15-day mortality similar to those found in ISIS-1.^[3] Both of these trials were performed in patients who did not receive acute reperfusion therapy, which is currently the standard of care for patients with ST-segment elevation MI.

Later studies assessed beta-blockers in patients receiving reperfusion therapy. The Thrombolysis in Myocardial Infarction Phase II (TIMI-II) trial compared early treatment with metoprolol (IV followed by oral) with oral metoprolol started six days after presentation in patients who received thrombolytic therapy.^[4] Patients treated early had lower rates of reinfarction and recurrent ischemia. The outcome of death and reinfarction was reduced in those patients who were treated particularly early (i.e. within 2 hours) with intravenous metoprolol. In contrast, other studies of early beta-blockade were not able to demonstrate the benefits of early intravenous treatment (TIMI-IIB, and a post-hoc analysis of the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries or GUSTO-I).^[5][6]

The data for patients with other acute coronary syndromes (ACS), including non-ST-segment elevation MI (NSTEMI) and unstable angina are less well established. However, a summary analysis of randomized trials with threatened or evolving MI showed lower rates of progression to MI with beta-blocker treatment.^[7]

Based upon these data, the current guidelines for ST-elevation MI give the highest recommendation (Class I) to oral beta-blocker therapy administered promptly to patients without a contraindication regardless of whether or not reperfusion therapy is provided. Intravenous beta-blockers are considered reasonable for patients without a contraindication, particularly in patients with high heart rates or blood pressures. This latter recommendation is considered IIa (i.e. where there is conflicting evidence or divergent opinion, but where the weight of the evidence is in favor of efficacy). Thus, although intravenous beta-blockers are not necessarily recommended for all patients, the early treatment of all patients without contraindications with a beta-blocker is strongly supported by evidence and guidelines. For patients with NSTEMI, the guidelines provide the highest recommendation to beta-blockers, initially intravenously and then orally, if there is ongoing chest pain and no contraindications to therapy.^[8]

Although beta-blockers may be useful in many patients with AMI, some patients have contraindications to the use of this class of drugs. Relative contraindications include heart rate <60 bpm, systolic blood pressure <100 mmHg, moderate or severe left ventricular failure, shock, PR-interval on the electrocardiogram >0.24 seconds, second- or third-degree heart block, active asthma/reactive airways disease.

ACC/AHA/AHRQ/CMS/JCAHO Practice Advisory

Commitment to Respond to COMMIT/CCS-2 Trial Beta Blocker Use for Myocardial Infarction (MI) Within 24 Hours of Hospital Arrival

At the American College of Cardiology Annual Scientific Session '05 in Orlando, the COMMIT/CCS-2 trial results evaluating the use of metoprolol for the emergency treatment of ST elevation myocardial infarction were presented. As the largest clinical trial ever undertaken in China and the second largest trial ever conducted in this patient population in the world, the preliminary results have raised questions about the use of beta blockers (IV then oral dosing) in the early stages of MI, especially in Killip Class II and III heart failure patients.

The American College of Cardiology, American Heart Association, Agency for Healthcare Research and Quality, Centers for Medicare and Medicaid Services, and the Joint Commission on Accreditation of Healthcare Organizations have begun an initial review of the presentation findings from the COMMIT/CCS-2 trial. In support of national efforts to develop a common set of performance measures, discussions of the impact of this trial on the intent and specifications for the relevant measure are being undertaken jointly.

Since all the details of the methodology and the final results from COMMIT/CCS-2 are not yet available nor peer reviewed and published, it is too early to state definitively whether or not changes will be required for performance measure specifications. The practicing community is reminded to review the current guidelines and performance measure specifications. These documents contain important information about contraindications and exclusion criteria for the use of beta blockers early in patients presenting with MI. Users of the measures are reminded that the measures have been constructed to allow for clinical judgment and documentation of reasons for not prescribing beta blockers. As such, the specifications are meant to encourage evidence-based care and to help clinicians avoid care oversights but do not mandate that everyone is treated in exactly the same way.

It is important to remember that a number of other trials have been conducted in this area and are currently reflected in both the guidelines and performance measures. Each patient should be evaluated in the context of all the information that has been published in the medical literature and in the current statements of the organizations represented in this advisory. It should be emphasized that beta blockers have been shown to provide important benefits to MI patients in the long term, a fact reinforced by the findings from the COMMIT/CCS-2 trial.

Our organizations are committed to issuing a timely response to this emerging evidence to ensure that relevant guidelines and performance measures reflect the current state of the science and support optimal patient care. Building upon relationships formed last year in updating the ACE inhibitor therapy measures to include angiotensin receptor blockers (ARBs), our organizations have begun an ongoing dialog to ensure that information is shared, evaluated, and responded to with a unified, timely and thorough response to clinical issues, such as those raised by this trial.

If further information or important patient safety issues are raised during our review prior to publication of the trial, an additional advisory will be issued. A final follow-up statement will be released shortly after the publication of the COMMIT/CCS-2 trial results advising the community about the findings from our review and its impact on performance measurement specifications.

Evidence-based medicine, as well as the guidelines and performance measures which derive from its foundation, have had a transformational effect on improving health care for all patients for more than a decade. However, each new trial reminds all stakeholders as clinical evidence changes, guidelines and measures must be continually reexamined. The ultimate goal is never simply to treat to a prescribed number but rather to achieve excellence by perfecting the care of each individual patient.

Questions and Answers

• Question

How are heart failure patients with AMI handled in the CMS/JCAHO beta-blocker measures?

Answer

In the 'Beta Blocker on Arrival' measure (AMI-6), patients with documented heart failure on arrival or within 24 hours of arrival are automatically excluded from the measure, regardless of whether they received a beta blocker, via any route. Terminology considered synonymous with heart failure is extensive (see 'Contraindication to Beta Blocker on Arrival' definition for more details):

• biventricular failure
• cardiac decompensation
• cardiac failure
• congestive heart failure (CHF)
• edema described as alveolar, diffuse interstitial, diffuse interstitial pulmonary, interstitial, pulmonary, or pulmonary interstitial
• edema of the lungs
• edema not described as pulmonary in nature, if referenced as chest x-ray finding (e.g., "CXR shows mild edema")
• fluid overload
• heart failure described as left, right, or unspecified
• perihilar congestion
• pulmonary congestion
• pump failure
• vascular congestion
• venous congestion
• ventricular failure
• volume overload
• wet lungs

Please note that chest x-ray reports are excluded sources in data collection—but MD/NP/PA references to chest x-ray findings are acceptable.

AMI patients with heart failure are not automatically excluded from the Beta Blocker at Discharge measure (AMI-5). If an MD/NP/PA documents that he/she did not prescribe beta blockers at discharge because of the patient's heart failure, the case will be excluded.

• Question

Will the CMS/JCAHO measure be changed as a result of the findings from the COMMIT/CCS-2 study?

Answer

We are aware of this study and CMS, JCAHO, ACC, AHA and AHRQ are working together to address these findings. For details, go to ACC/AHA/AHRQ/CMS/JCAHO Practice Advisory.

References

1. ↑ Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, Hochman JS, Krumholz HM, Kushner FG, Lamas GA, Mullany CJ, Ornato JP, Pearle DL, Sloan MA, Smith SC, Jr., Alpert JS, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Gregoratos G, Halperin JL, Hiratzka LF, Hunt SA, Jacobs AK. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction—executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). Circulation 2004;110(5):588-636.
2. ↑ Randomised trial of intravenous atenolol among 16,027 cases of suspected acute myocardial infarction: ISIS-1. Lancet 1986;2(8498):57-66.
3. ↑ Metoprolol in acute myocardial infarction. Patient population. The MIAMI Trial Research Group. Am J Cardiol 1985;56(14):10G-4G.
4. ↑ Comparison of invasive and conservative strategies after treatment with intravenous tissue plasminogen activator in acute myocardial infarction. Results of the thrombolysis in myocardial infarction (TIMI) phase II trial. N Engl J Med 1989;320(10):618-27.
5. ↑ Roberts R, Rogers WJ, Mueller HS, Lambrew CT, Diver DJ, Smith HC, Willerson JT, Knatterud GL, Forman S, Passamani E. Immediate versus deferred beta-blockade following thrombolytic therapy in patients with acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) II-B Study. Circulation 1991;83(2):422-37.
6. ↑ Pfisterer M, Cox JL, Granger CB, Brener SJ, Naylor CD, Califf RM, Van de Werf F, Stebbins AL, Lee KL, Topol EJ, Armstrong PW. 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. J Am Coll Cardiol 1998;32(3):634-40.
7. ↑ Yusuf S, Wittes J, Friedman L. Overview of results of randomized clinical trials in heart disease. II. Unstable angina, heart failure, primary prevention with aspirin, and risk factor modification. JAMA 1988;260(15):2259-63.
8. ↑ Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, Jones RH, Kereiakes D, Kupersmith J, Levin TN, Pepine CJ, Schaeffer JW, Smith EE, III, Steward DE, Theroux P, Gibbons RJ, Antman EM, Alpert JS, Faxon DP, Fuster V, Gregoratos G, Hiratzka LF, Jacobs AK, Smith SC, Jr. ACC/AHA Guideline Update for the Management of Patients With Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction-2002: Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). Circulation 2002;106(14):1893-90

American College of Cardiology Foundation

American Health Association

Agency for Healthcare Research and Quality

Centers for Medicare & Medicaid Services

Joint Commission of Healthcare Organizations