Carvedilol
Carvedilol is a non-selective beta-blocker with alpha1-adrenergic receptor antagonist properties, indicated for the chronic therapy of heart failure with reduced ejection fraction (HFrEF), hypertension, and left ventricular dysfunction following myocardial infarction in clinically stable patients. It is a non-selective, cardiac beta-blocker with peripheral vasodilating effects
Off-label indications for carvedilol include stable angina, atrial fibrillation, and cirrhotic esophageal variceal bleeding prophylaxis, and ventricular arrhythmias.
The 2017 ACC/AHA/HRS (American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society) guideline continues to recommend carvedilol (immediate or extended-release) as a beta-blocker of choice for HFrEF.
Several studies support this recommendation, but most importantly, it has support from the COPERNICUS trial published in 2002. This particular study found that carvedilol reduces the risk of death and hospitalizations for heart failure by 31% compared to a placebo group in patients with New York Heart Association class III and IV heart failure with an ejection fraction less than 25%.
Another paramount study is the COMET trial published in 2003, which compared carvedilol to metoprolol tartrate. This study showed that carvedilol reduced all-cause mortality compared to metoprolol tartrate in patients with HFrEF and an ejection fraction of equal to 35%. Criticism revolves around these results. Although the COMET trial compared carvedilol to metoprolol, it should be understood that patients randomized to receive metoprolol received metoprolol tartrate at 50 mg twice daily; this was an alternate and underdosed form of metoprolol that was not used in the MERIT-HF trial that showed a reduction in all-cause mortality with metoprolol succinate at 200 mg daily. This result highlights a common topic between these two beta-blockers in the treatment of heart failure. Further studies have shown no difference between carvedilol and metoprolol succinate in all-cause mortality or hospitalizations and a difference in favor of metoprolol succinate, although these were not randomized trials but meta-analysis and observational studies, respectively. Evidence to support carvedilol’s use in left ventricular dysfunction following a myocardial infarction (MI) is established by the CAPRICORN trial published in 2001. This study found a decrease in all-cause mortality in patients with left ventricular dysfunction following an acute MI.
Off-label indications for carvedilol include stable angina, atrial fibrillation, and cirrhotic esophageal variceal bleeding prophylaxis, and ventricular arrhythmias. These “off-label” uses can be extrapolated across most beta-blockers rather than just carvedilol alone.
For example, stable angina gets treated with beta-blockers, with an anti-anginal therapy target heart rate of 55 to 60, regardless of which beta-blocker is used. Rate control therapy in atrial fibrillation is also achievable with nearly any beta-blocker. Note that specific beta-blockers other than carvedilol are preferable for use in esophageal variceal bleeding prevention; however, some studies have suggested that carvedilol may be more effective in decreasing hepatic venous pressure or preventing variceal bleeding than other beta-blockers.