Physicians' Academy for Cardiovascular Education

Cardioprotective effect of Beta-blockers questioned

Literature - Bangalore S, Steg G, Deedwania P, et al; REACH Registry Investigators, JAMA. 2012;

β-Blocker use and clinical outcomes in stable outpatients with and without coronary artery disease.

Bangalore S, Steg G, Deedwania P, et al; REACH Registry Investigators.

JAMA. 2012;308:1340-9. doi: 10.1001/jama.2012.12559.

Background

For patients with coronary artery disease, β-blockers remain the standard of care, especially after a myocardial infarction (MI) [1,2]. The evidence from post-MI or heart failure trials has been extrapolated to patients with CAD or at high risk for CAD. It is not clear whether use of beta-blockers will lead to a lower risk of composite CV events in patients with CAD risk factors only, known prior MI or known CAD without MI. A longitudinal, observational study of patients in the Reduction of Atherothrombosis for Continued Health (REACH) registry was therefore conducted. Patients were divided into three cohorts: known prior MI (n=14,043), known CAD without MI (n=12,012) or those with CAD risk factors only (n=18,653). Primary outcome were defined as a composite of CV death, nonfatal MI or nonfatal stroke, and the secondary outcome as the primary outcome plus hospitalization for atherothrombotic events or a revascularization procedure.


Main results

Beta-blocker use was not associated with a significant difference in the rate of cardiovascular death, nonfatal MI, or nonfatal stroke:

CAD patients with prior MI:

  • 16.93% in the beta-blocker group versus 18.60% in the controls, hazard ratio [HR] 0.90, CI 0.79-1.03, p = 0.14

CAD patients without prior MI:

  • 12.94% versus 13.55%, HR 0.92, CI 0.79-1.08, p= 0.31

Patients with risk factors only:

  • 14.22% versus 12.11%, HR 1.18, CI 1.02-1.36, p = 0.02

Fig. 1. Cumulative incidence curve for the risk of primary outcome by β-blocker use


Conclusion

β-Blocker use was not associated with a lower event rate of cardiovascular events at 44-month follow-up, even among patients with prior history of MI, which is consistent with the recently updated American Heart Association secondary prevention guidelines in which beta-blocker therapy is a class I recommendation only for HF, MI or ACS for up to 3 years after MI, but is a class IIa recommendation for longer-term therapy.

Further research is warranted to identify subgroups that benefit from β-blocker therapy and the optimal duration of β-blocker therapy.


Fig. 1-3. Cumulative incidence curve for the risk of primary outcome by β-blocker use

References

  1. Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet. 2001;357:1385-1390.
  2. Chen J, Radford MJ, Wang Y, et al. Are β-blockers effective in elderly patients who undergo coronary revascularization after acute myocardial infarction? Arch Intern Med. 2000; 160:947-952.

Abstract

Context:
β-Blockers remain the standard of care after a myocardial infarction (MI). However, the benefit of β-blocker use in patients with coronary artery disease (CAD) but no history of MI, those with a remote history of MI, and those with only risk factors for CAD is unclear.

Objective:
To assess the association of β-blocker use with cardiovascular events in stable patients with a prior history of MI, in those with CAD but no history of MI, and in those with only risk factors for CAD.

Design, setting, and patients:
Longitudinal, observational study of patients in the Reduction of Atherothrombosis for Continued Health (REACH) registry who were divided into 3 cohorts: known prior MI (n = 14,043), known CAD without MI (n = 12,012), or those with CAD risk factors only (n = 18,653). Propensity score matching was used for the primary analyses. The last follow-up data collection was April 2009.

Main outcome measures:
The primary outcome 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.

Results:
Among the 44,708 patients, 21,860 were included in the propensity score-matched analysis. With a median follow-up of 44 months (interquartile range, 35-45 months), event rates were not significantly different in patients with β-blocker use compared with those without β-blocker use for any of the outcomes tested, even in the prior MI cohort (489 [16.93%] vs 532 [18.60%], respectively; hazard ratio [HR], 0.90 [95% CI, 0.79-1.03]; P = .14). In the CAD without MI cohort, the associated event rates were not significantly different in those with β-blocker use for the primary outcome (391 [12.94%]) vs without β-blocker use (405 [13.55%]) (HR, 0.92 [95% CI, 0.79-1.08]; P = .31), with higher rates for the secondary outcome (1101 [30.59%] vs 1002 [27.84%]; odds ratio [OR], 1.14 [95% CI, 1.03-1.27]; P = .01) and for the tertiary outcome of hospitalization (870 [24.17%] vs 773 [21.48%]; OR, 1.17 [95% CI, 1.04-1.30]; P = .01). In the cohort with CAD risk factors only, the event rates were higher for the primary outcome with β-blocker use (467 [14.22%]) vs without β-blocker use (403 [12.11%]) (HR, 1.18 [95% CI, 1.02-1.36]; P = .02), for the secondary outcome (870 [22.01%] vs 797 [20.17%]; OR, 1.12 [95% CI, 1.00-1.24]; P = .04) but not for the tertiary outcomes of MI (89 [2.82%] vs 68 [2.00%]; HR, 1.36 [95% CI, 0.97-1.90]; P = .08) and stroke (210 [6.55%] vs 168 [5.12%]; HR, 1.22 [95% CI, 0.99-1.52]; P = .06). However, in those with recent MI (≤1 year), β-blocker use was associated with a lower incidence of the secondary outcome (OR, 0.77 [95% CI, 0.64-0.92]).

Conclusion:
In this observational study of patients with either CAD risk factors only, known prior MI, or known CAD without MI, the use of β-blockers was not associated with a lower risk of composite cardiovascular events.

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