Best beta-blocker for heart failure

During my training, the use of beta-blockers was considered to cause potential harm among patients with heart failure. However, I worked with seasoned cardiologists at Mayo who were convinced of the contrary even before large amounts of data began to emerge supporting their use.

Analyses of the Studies of Left Ventricular Dysfunction (SOLVD) ultimately taught us that the combination of beta-blockers (BBs) and enalapril was associated with a reduction in risk of death. Large meta-analyses also identified reduction in morbidity and mortality, and suggested that they should be routinely offered to all patients with heart failure (HF).

As others have said before me, not all BBs are treated equally. BBs with intrinsic sympathomimetic activity (e.g., acebutolol and pindolol) should generally be avoided in patients with HF. But do clinically important differences exist between BBs with beta-nonselective activity (carvedilol) and beta₁-selective activity (e.g., atenolol and metoprolol) in patients with HF and acute myocardial infarction (AMI)?

James DiNicolantonio, Pharm.D., and his colleagues conducted a systematic review and meta-analysis comparing outcomes between clinical trial subjects with systolic HF or AMI receiving carvedilol and those receiving beta₁-selective BBs (specifically atenolol, metoprolol, bisoprolol, and nebivolol) (Am. J. Cardiol. 2013 Jan. 7 [doi: 10.1016/j.amjcard.2012.11.031]).

Studies were included if they were randomized, controlled clinical trials including adults older than 18 years. Outcomes included all-cause mortality, cardiovascular events including fatal and nonfatal strokes and MI, HF, and CV-related hospital readmissions. Eleven studies were included in the final meta-analyses.

A significant decrease in all-cause mortality in patients with HF was observed with carvedilol, compared with beta₁-selective BBs (relative risk, 0.85; 95% confidence interval, 0.78-0.93; number needed to treat = 22). In patients with AMI, carvedilol significantly decreased all-cause mortality by 45% (RR, 0.55; 95% CI, 0.32-0.94), compared with beta₁-selective BBs.

No statistically significant benefit of carvedilol was observed for HF readmissions or nonfatal MI in patients with AMIs.

The investigators remind us that in addition to being a beta-nonselective BB and an alpha₁-blocker, carvedilol may have unique vasodilating, antioxidant, and antiarrhythmic effects. The combination of these effects may account for the observed differences.

Dr. DiNicolantonio also highlights our current use and misuse of atenolol. Atenolol continues to be one of the most widely prescribed BBs. This is occurring in spite of the fact that atenolol has not been shown to improve CV prognosis after MI, improve outcomes in HF, or reduce the risk for heart disease despite blood pressure lowering.

Many clinics, including my own, have reminder systems for clinicians to consider the use of ACE-I therapy for patients with HF. To improve patient outcomes, these systems should remind us to consider carvedilol, or at least consider it in lieu of beta₁-selective BBs.

Dr. Ebbert is professor of medicine and primary care clinician at the Mayo Clinic in Rochester, Minn. The opinions expressed are solely those of the author.

During my training, the use of beta-blockers was considered to cause potential harm among patients with heart failure. However, I worked with seasoned cardiologists at Mayo who were convinced of the contrary even before large amounts of data began to emerge supporting their use.

Analyses of the Studies of Left Ventricular Dysfunction (SOLVD) ultimately taught us that the combination of beta-blockers (BBs) and enalapril was associated with a reduction in risk of death. Large meta-analyses also identified reduction in morbidity and mortality, and suggested that they should be routinely offered to all patients with heart failure (HF).

As others have said before me, not all BBs are treated equally. BBs with intrinsic sympathomimetic activity (e.g., acebutolol and pindolol) should generally be avoided in patients with HF. But do clinically important differences exist between BBs with beta-nonselective activity (carvedilol) and beta₁-selective activity (e.g., atenolol and metoprolol) in patients with HF and acute myocardial infarction (AMI)?

James DiNicolantonio, Pharm.D., and his colleagues conducted a systematic review and meta-analysis comparing outcomes between clinical trial subjects with systolic HF or AMI receiving carvedilol and those receiving beta₁-selective BBs (specifically atenolol, metoprolol, bisoprolol, and nebivolol) (Am. J. Cardiol. 2013 Jan. 7 [doi: 10.1016/j.amjcard.2012.11.031]).

Studies were included if they were randomized, controlled clinical trials including adults older than 18 years. Outcomes included all-cause mortality, cardiovascular events including fatal and nonfatal strokes and MI, HF, and CV-related hospital readmissions. Eleven studies were included in the final meta-analyses.

A significant decrease in all-cause mortality in patients with HF was observed with carvedilol, compared with beta₁-selective BBs (relative risk, 0.85; 95% confidence interval, 0.78-0.93; number needed to treat = 22). In patients with AMI, carvedilol significantly decreased all-cause mortality by 45% (RR, 0.55; 95% CI, 0.32-0.94), compared with beta₁-selective BBs.

No statistically significant benefit of carvedilol was observed for HF readmissions or nonfatal MI in patients with AMIs.

The investigators remind us that in addition to being a beta-nonselective BB and an alpha₁-blocker, carvedilol may have unique vasodilating, antioxidant, and antiarrhythmic effects. The combination of these effects may account for the observed differences.

Dr. DiNicolantonio also highlights our current use and misuse of atenolol. Atenolol continues to be one of the most widely prescribed BBs. This is occurring in spite of the fact that atenolol has not been shown to improve CV prognosis after MI, improve outcomes in HF, or reduce the risk for heart disease despite blood pressure lowering.

Many clinics, including my own, have reminder systems for clinicians to consider the use of ACE-I therapy for patients with HF. To improve patient outcomes, these systems should remind us to consider carvedilol, or at least consider it in lieu of beta₁-selective BBs.

Dr. Ebbert is professor of medicine and primary care clinician at the Mayo Clinic in Rochester, Minn. The opinions expressed are solely those of the author.

During my training, the use of beta-blockers was considered to cause potential harm among patients with heart failure. However, I worked with seasoned cardiologists at Mayo who were convinced of the contrary even before large amounts of data began to emerge supporting their use.

Analyses of the Studies of Left Ventricular Dysfunction (SOLVD) ultimately taught us that the combination of beta-blockers (BBs) and enalapril was associated with a reduction in risk of death. Large meta-analyses also identified reduction in morbidity and mortality, and suggested that they should be routinely offered to all patients with heart failure (HF).

As others have said before me, not all BBs are treated equally. BBs with intrinsic sympathomimetic activity (e.g., acebutolol and pindolol) should generally be avoided in patients with HF. But do clinically important differences exist between BBs with beta-nonselective activity (carvedilol) and beta₁-selective activity (e.g., atenolol and metoprolol) in patients with HF and acute myocardial infarction (AMI)?

James DiNicolantonio, Pharm.D., and his colleagues conducted a systematic review and meta-analysis comparing outcomes between clinical trial subjects with systolic HF or AMI receiving carvedilol and those receiving beta₁-selective BBs (specifically atenolol, metoprolol, bisoprolol, and nebivolol) (Am. J. Cardiol. 2013 Jan. 7 [doi: 10.1016/j.amjcard.2012.11.031]).

Studies were included if they were randomized, controlled clinical trials including adults older than 18 years. Outcomes included all-cause mortality, cardiovascular events including fatal and nonfatal strokes and MI, HF, and CV-related hospital readmissions. Eleven studies were included in the final meta-analyses.

A significant decrease in all-cause mortality in patients with HF was observed with carvedilol, compared with beta₁-selective BBs (relative risk, 0.85; 95% confidence interval, 0.78-0.93; number needed to treat = 22). In patients with AMI, carvedilol significantly decreased all-cause mortality by 45% (RR, 0.55; 95% CI, 0.32-0.94), compared with beta₁-selective BBs.

No statistically significant benefit of carvedilol was observed for HF readmissions or nonfatal MI in patients with AMIs.

The investigators remind us that in addition to being a beta-nonselective BB and an alpha₁-blocker, carvedilol may have unique vasodilating, antioxidant, and antiarrhythmic effects. The combination of these effects may account for the observed differences.

Dr. DiNicolantonio also highlights our current use and misuse of atenolol. Atenolol continues to be one of the most widely prescribed BBs. This is occurring in spite of the fact that atenolol has not been shown to improve CV prognosis after MI, improve outcomes in HF, or reduce the risk for heart disease despite blood pressure lowering.

Many clinics, including my own, have reminder systems for clinicians to consider the use of ACE-I therapy for patients with HF. To improve patient outcomes, these systems should remind us to consider carvedilol, or at least consider it in lieu of beta₁-selective BBs.

Dr. Ebbert is professor of medicine and primary care clinician at the Mayo Clinic in Rochester, Minn. The opinions expressed are solely those of the author.