Investigators tried a different strategy of starting carvedilol before discharge in hospitalized heart failure patients. The pre-discharge carvedilol strategy significantly increased the use of beta-blockers compared with standard post-discharge initiation of beta-blockers. There was no excess of side effects and no increase in length of stay. Pre-discharge initiation of carvedilol may increase the use of potentially life-saving therapy in this population.

Large, prospective, randomized trials show that certain beta-blockers reduce morbidity and mortality in heart failure patients. In addition, published guidelines recommend their use in this setting.

However, only about 30% to 40% of eligible heart failure patients actually receive this potentially life-saving therapy. One problem is that a "vicious cycle" limits use of beta-blockers in heart failure patients, Dr. Gheorghiade said. Guidelines recommend waiting 2 to 4 weeks after hospitalization before initiating beta-blocker therapy. However, after discharge, the patient is often unlikely to receive a prescription. This may be because the primary care physician is reluctant to prescribe the medication. Some physicians may believe a prescription is not necessary if it is not part of the discharge regimen.

New strategies to break this vicious cycle may help broaden the use of beta-blockers in heart failure patients. One possible way is to initiate beta-blocker therapy before discharge. This strategy would contradict current guidelines, which suggest waiting until after hospitalization to initiate beta-blockers. On the other hand, data from the COPERNICUS trial suggest carvedilol is safe and effective soon after its initiation, even in patients who have severe heart failure.

Thus, Dr. Gheorghiade and colleagues studied the safety of initiating carvedilol therapy prior to discharge. They initiated a prospective, randomized, open-label trial, IMPACT-HF (Initiation Management Predischarge: process for Assessment of Carvedilol Therapy for Heart Failure).

The IMPACT-HF trial was a multi-center study including 363 patients who were hospitalized for worsening heart failure. All patients had a left ventricular ejection fraction of 40% or less. Some were randomized to pre-discharge carvedilol started at a low dose (3.125 mg bid). The rest received standard care, which was post-discharge beta-blocker at the physician's discretion. The primary endpoint was the number of patients who received beta-blocker at 60 days.

Baseline characteristics were similar between the two groups.

The most common comorbidities included hypertension, diabetes and hyperlipidemia. Both patient groups were similar in terms of heart failure signs and symptoms, NYHA class (mostly III-IV), edema, and medications at baseline.

Beta-blocker Initiation

More patients in the pre-discharge carvedilol group received a beta-blocker than in the group that received post-discharge beta-blocker initiation at the physician's discretion. According to Dr. Gheorghiade, 91% of patients in the pre-discharge carvedilol group were on beta-blockers at 60 days, compared with 73% in the post-discharge group (p < 0.0001). Mean time to first beta-blocker initiation in the post-discharge group was 20.3 days.

Beta-blocker Dosage

In addition, significantly more patients randomized to pre-discharge carvedilol were receiving a higher dose at 60 days. Investigators found that 36% of the pre-discharge carvedilol group reached the mean target dose, compared with 29% of the post-discharge group (p = 0.0183).

Clinical Outcomes

Pre-discharge initiation of carvedilol was not associated with an increased risk of worsening heart failure (9%, versus 14% in the post-discharge group) or other serious adverse events. In fact, there was a trend toward less death/rehospitalization in the carvedilol pre-discharge group.

Pre-discharge carvedilol did not adversely impact length of stay. The mean hospital stay was 5.9 versus 6.6 days for the pre- and post-discharge groups, respectively.

These results suggest that pre-discharge initiation of carvedilol in stabilized heart failure patients can increase use of beta-blocker therapy. Investigators achieved this improvement without increasing the side effect burden, or length of stay. Pre-discharge initiation of carvedilol may be a practical approach to improving the use of potentially life-saving therapy in this population.