Rethinking Beta-blockers

Rethinking the Utility of Beta-blockers

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It may be time to rethink the long-term use of beta-blockers in your patients who have a history of cardiovascular disease. Among patients who have: 1) risk factors for coronary artery disease (CAD), 2) have suffered a prior heart attack, or 3) have CAD without heart attack, the use of beta-blockers was not associated with a lower risk of a composite of cardiovascular events, according to a new study published in JAMA.[1]

This finding is notable because treatment with beta-blockers remains the standard of care for patients with CAD, especially followed by a myocardial infarction (MI). Evidence for this practice is derived from relatively old post-MI studies, most of which preceded the implementation of current reperfusion or medical therapy, and from heart failure trials. According to background information in the article, the data from these older studies have been widely extrapolated to patients with CAD and even to patients at high risk for but without established CAD. However, it is not known if these extrapolations are justified. In addition, the long-term efficacy of these agents in patients treated with contemporary medical therapies is not known, even in patients with prior MI.

A team of researchers from the NYU School of Medicine conducted a study to evaluate the association between beta-blocker use and long-term cardiovascular outcomes, which included cardiovascular death, nonfatal heart attack or nonfatal stroke. The observational study included data from patients in the Reduction of Atherothrombosis for Continued Health (REACH) registry. From this registry, 44,708 patients met the study inclusion criteria of whom 14,043 patients (31%) had a prior MI, 12,012 patients (27%) had documented CAD but without MI, and 18,653 patients (42%) had CAD risk factors only. The last follow-up data collection was April 2009.

The primary outcome for this study was a composite of cardiovascular death, nonfatal MI, or nonfatal stroke. The secondary outcome was the primary outcome plus hospitalization for atherothrombotic events or a revascularization procedure. The overall median (midpoint) follow-up was 44 months. Among the 44,708 patients in the study, 21,860 were included in the propensity score-matched analysis.

The researchers found that in the prior MI group, event rates were not significantly different among those with beta-blocker use (489 [17%) compared with those who did not take beta-blockers (532 [18%]) for the primary outcome or the secondary outcome (31% percent versus 33%, respectively). In the CAD without MI cohort, event rates were similar in those with beta-blocker use (391 [13%]) versus those who did not take beta-blockers (405 [13.55%]) for the primary outcome, for cardiovascular death, for stroke, and for MI. Event rates were higher in those who took beta-blockers (1,101 [31%] versus those who did not (1,002 [28%]) for the secondary outcome and for hospitalization in the propensity score-matched model.

In the group who had risk factors alone, event rates were higher in those with beta-blocker use (467 [14.22%]) versus those without beta-blocker use (403 [12%]) for the primary outcome, for the secondary outcome (870 [22%] versus 797 [20%], respectively), but not for MI or stroke. In the propensity score-matched model, there were similar event rates for cardiovascular death and for hospitalization.

The researchers also found that among patients with recent MI (1 year or less), beta-blocker use was associated with a lower incidence of the secondary outcome (the primary outcome plus hospitalization for atherothrombotic events or a revascularization procedure).

Limitations of the study included a lack of information as to the type of beta-blockers patients were taking, the dosage, or the reason patients had not been prescribed a beta-blocker. The researchers also had very little information relative to the type of MI or prior beta-blocker use.

Several international healthcare organizations, including the American Heart Association (AHA) and the European Society of Cardiology (ESC) have already updated their secondary prevention guidelines.[2][3] The AHA now recommends beta-blocker therapy as a class I recommendation for heart failure, MI, or acute coronary syndrome for up to 3 years after MI, but is a class II recommendation for longer-term therapy. Treatment with beta-blockers was also downgraded to a class IIB recommendation for all other patients with coronary or other vascular disease. Similarly, the updated 2011 European Society of Cardiology prevention guidelines now recommend the long-term use of beta-blockers only for patients with reduced left ventricular systolic function. Beta-blocker therapy has also been downgraded by the European Society on Hypertension, the American Heart Association, and others to a fourth-line agent for the treatment of hypertension.[4][5]

Why this sudden change in heart? The researchers hypothesize that despite long-standing pivotal evidence that beta-blockers reduce mortality, the data are somewhat misleading. In a large meta-analysis published in 1999, there was a 23% reduction in deaths noted among the trials where beta-blockers were used.[6] However, the mean follow-up was only 1.4 years and the median publication date of the 82 randomized trials selected was 1982. As well, most of the trials in the meta-analysis were performed in the era before modern reperfusion or medical therapy was routine treatment for patients who had a MI. It may be that these newer medical therapies—including aspirin, lipid-lowering agents, and ACE-inhibitors—may protect the heart muscle efficiently enough so as to make beta-blockers redundant. In addition, many patients have trouble tolerating beta-blockers because of their adverse effects, including dizziness, fatigue, nausea, diarrhea, coldness of the extremities, headache, and sexual dysfunction. In fact, one study suggests that among 17,035 patients who had a MI, only 45% of patients were adherent to their beta-blockers after 1 year.

The researchers concluded that among patients enrolled in the international REACH registry, the use of beta-blockers was not associated with a lower event rate of cardiovascular events at 44-months follow-up, even among patients with prior history of MI. The authors call for further research to identify subgroups that may benefit from beta-blocker therapy as well as the optimal duration of beta-blocker therapy.

 

Jill Shuman, MS, ELS
Published on November 27, 2012

References

  1. Bangalore S, Steg PH, Deedwania P, et al. β-blocker use and clinical outcomes in stable outpatients with and without coronary artery disease. JAMA. 2012;308:1340-1349.
  2. Smith SC Jr, Benjamin EJ, Bonow RO, et al. World Heart Federation and the Preventive Cardiovascular Nurses Association. AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2011 update: A guideline from the American Heart Association and American College of Cardiology Foundation. Circulation. 2011;124(22):2458-2473.
  3. Hamm CW, Bassand JP, Agewall S, et al. ESC Committee for Practice Guidelines; Document Reviewers. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The task force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2011;32(23):2999-3054.
  4. Mancia G, De Backer G, Dominiczak A, et al. Task force for the management of arterial hypertension of the European Society of Hypertension; Task force for the management of arterial hypertension of the European Society of Cardiology. 2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2007;28(12):1462-1536.
  5. Rosendorff C, Black HR, Cannon CP, et al. American Heart Association Council for High Blood Pressure Research; American Heart Association Council on Clinical Cardiology; American Heart Association Council on Epidemiology and Prevention. Treatment of hypertension in the prevention and management of ischemic heart disease: A scientific statement from the American Heart Association Council for High Blood Pressure Research and the Councils on Clinical Cardiology and Epidemiology and Prevention. Circulation. 2007;115(21):2761-2788.
  6. Freemantle N, Cleland J, Young P, Mason J, Harrison J. Beta blockade after myocardial infarction: Systematic review and meta regression analysis. BMJ. 1999;318(7200):1730-1737.