CHICAGO - November 2002 - Initiating low-dose beta-blockers prior to discharge in heart failure patients hospitalized for worsening symptoms significantly improves the use of a drug that has been shown in previous studies to reduce death and morbidity by more than 35 percent.
This finding is significant, said researchers from Duke University Medical Center and Northwestern University, because standard heart failure practice guidelines suggest waiting a period of two to four weeks after discharge prior to initiating beta-blocker therapy. This recommendation was based on a concern that beta-blocker initiation too soon after a hospitalization for heart failure may worsen heart failure symptoms, said the researchers.
Beta-blockers block the stimulatory effects of the neurohormones epinephrine and norepinephrine, the so-called "fight-or-flight" hormones. By blocking these hormones, beta-blockers reduce the stress on the heart and reverse myocardial remodeling. Most importantly, they have been shown to improve survival and reduce the need for hospitalization by 35 percent in several large-scale, prospective, randomized clinical trials. Despite these beneficial effects, it is estimated that nationally still only 30 to 40 percent of eligible patients receive beta-blocker therapy.
Such low usage led the researchers to initiate a trial to determine whether starting beta-blocker therapy in the hospital setting would improve usage. The results of that trial, reported today (Nov. 18, 2002) at the 75th annual scientific session of the American Heart Association, show that beginning beta-blocker therapy in-hospital can achieve a 91 percent usage rate 60 days after discharge.
"If we can dramatically improve the rate of beta-blocker usage by initiating therapy in-hospital, that would make a major impact these patients' lives," said Duke cardiologist Christopher O'Connor, M.D., who along with Duke's Wendy Gattis, Pharm.D., and Northwestern's Mihai Gheorghiade, M.D., directed the trial.
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"Strategies like this are extremely important as the death and disability of this group of patients continues to be alarmingly high despite the availability of life-saving therapies," O'Connor said.
Heart failure is marked by the inability of the heart muscles to pump enough oxygen and nutrients in the blood to the body's tissues. Also known as congestive heart failure, its many causes include coronary artery disease, high blood pressure, previous heart attack and valve problems.
An estimated 4.7 million Americans suffer from heart failure, with 500,000 new cases reported each year, and according to the researchers, it is the only cardiovascular disease that is rising in incidence. Once diagnosed with heart failure, about 50 percent of patients will die within five years.
For the trial, the researchers randomized 363 heart failure patients to one of two groups: one received the beta-blocker carvedilol prior to hospital discharge, while the other group could receive a beta-blocker at their physician's discretion, but it could not be started until at least two weeks after discharge, according to current standard practice. After 60 days, 91 percent of patients who were started on carvedilol prior to hospital discharge were still taking a beta-blocker, while 73 percent of physician-discretion group were taking them, a difference that was highly statistically significant.
In addition, patients initiated on carvedilol pre-discharge were closer to reaching the target beta-blocker dose at 60-days as compared to the patients in the post-discharge physician discretion arm, a finding that was also statistically significant.
"Not only was the usage rate higher, but we showed that early beta-blocker treatment was safe," Gattis said. "The patients initiated on carvedilol prior to discharge did not have a higher rate of serious adverse events including worsening heart failure, hypotension, or bradycardia as compared to the patients initiated post-discharge. Other important clinical events such as death or rehospitalizations were also less frequent at 60 days in the early treatment group, but because of small patient numbers and the short duration of follow-up did not reach statistical significance."
The safety issue is important, the researchers said, because until recently, initiation of beta-blockers was not recommended in patients with a recent episode of heart failure worsening. These new data should help encourage physicians to change long-held prescribing habits. The researchers said that many physicians, upon seeing their heart failure patients stabilized in-hospital, are hesitant to add another medication to the mix out of concern that patients' symptoms may worsen.
"We hope to change physicians' minds and get them to look at in-hospital beta-blocker use as a method to increase the overall use of beta-blockers in this population. Increased use of this evidence-based therapy will likely translate into improved outcomes for patients based on data from previous randomized trials," Gattis said.
O'Connor sees a similarity between the low rate of usage of beta-blockers for heart failure and another class of heart medications known as statins, which have been proven to lower cholesterol levels and, more importantly, to reduce the risk of death and myocardial infarction in patients with coronary heart disease.
"For a long time, the usage rate of statins was about 20 percent, even though clinical trials clearly demonstrated their effectiveness," O'Connor. "Then, later trials showed that it was not only safe to start statins in heart attack patients while still in the hospital, but that this early initiation of therapy led to a higher rate of use after discharge."
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Heart failure often leaves patients exhausted and breathless, and the normal activities of these patients can be severely restricted. Although there is no cure for the disorder, a variety of drugs are often used in the treatment of heart failure, including ACE-inhibitors, beta-blockers, diuretics and digoxin.
Patients with heart failure can be a difficult group to treat, said the researchers. They are frequently admitted to the hospital to care for the symptoms of the disease, and almost one-third will be re-admitted to the hospital within the first three months after discharge.
"It is hoped that implementing beta-blocker therapy early will ensure that patients are actually treated with evidence-based therapies, which indirectly should also contribute to improving outcomes for heart failure patients," Gattis said.
The current trial, dubbed Initiation Management Predischarge Process for Assessment of Carvedilol Therapy for Heart Failure (IMPACT-HF), was funded by GlaxoSmithKline, Philadelphia, the maker of carvedilol. O'Connor, Gattis, and Gheorghiade receive research support from and are consultants to GlaxoSmithKline.
Source: Duke University Medical Center and Northwestern University
