Nearly 5 million Americans are currently living with congestive heart failure (CHF). Approximately 550,000 new cases are diagnosed in the U.S. each year. More than 5 percent of people between the ages of 60 and 69 have CHF. The 1-year, 3-year, 5-year, and 10-year survival rates in the entire CHF group were 78.5%, 59.8%, 50.4% and 14.7%, respectively.
Medical therapy for CHF is the backbone of treatment modality for all CHF patients. Currently as per ACC/AHA recommendations all patients with CHF should be on a beta-blocker- medicines that block the beta receptors in the body. The FDA approved beta-blockers for CHF therapy are carvedilol, metoprolol succinate, and bisoprolol. Of these, the most common ones used in the US are carvedilol and metoprolol succinate.
These two beta-blockers are, pharmacologically, very different. While metoprolol succinate is a selective Beta-1 receptor blocker in the heart, carvedilol in non-selective. It has beta-1, beta-2, and alpha receptor blocking properties in addition to anti-oxidant properties. Thus, in addition to lowering heart rate and negative ionotropic effects, carvedilol also had vasodilatory effects which help in reducing afterload and is beneficial in patients with CHF. There has been no randomized, prospective trial comparing these two beta-blockers for the treatment of CHF. A few small retrospective post-hoc analyses of randomized trials have shown that there is no difference between the two in terms of survival in patients with CHF.
We analyzed data from the central VA database and identified patients who had reduced ejection fraction and CHF. These patients had an ejection fraction of less than 40% to be included in the study and were treated with either metoprolol succinate or carvedilol in addition to other heart failure medications. Since it was a retrospective study, we utilized propensity score matching to make the groups more comparable. The follow up the patients was up to 6 years. At end of follow up, we found that patients treated with carvedilol had a significantly higher probability of survival than patients treated with metoprolol succinate. We found that if 44 patients were treated with carvedilol instead of metoprolol succinate, one additional life would be saved.
Our study is the largest one done so far and has the longest follow up. However, as with all retrospective database studies, it has a number of confounders that can be addressed with conducting a prospective randomized trial comparing the two medications to assess what is the best beta blocker to use in CHF. Such a comparative efficacy trial will be easy to perform given the high prevalence of this disease and also because both the medications are now available in generic form. With this in mind, we have a proposal written up for such a trial which we are in the process of submitting to the veteran’s affairs cooperative study section for funding. The trial aims to follow patients for a one-year mean duration and is designed to look for survival benefit between the two beta blockers.We will also be looking for differences in rates of hospitalization for heart failure between the two drugs.
These findings are described in the article entitled Effect of carvedilol vs metoprolol succinate on mortality in heart failure with reduced ejection fraction, recently published in the American Heart Journal. This work was conducted by Tarek Ajam and Kahee Mohammed from the Saint Louis University School of Medicine, Samer Ajam, Stephen Sawada, and Masoor Kamalesh from the Krannert Institute of Cardiology, Indiana University School of Medicine, and Srikant Devaraj from Ball State University.