Initiation Management Predischarge: Process for Assessment of Carvedilol Therapy in Heart Failure - IMPACT-HF

Aug 30, 2004
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Date Published:
01/01/2004
Date Updated:
08/30/2004
Original Posted Date:
08/30/2004
References

Description:

The goal of the Initiation Management Predischarge: Process for Assessment of Carvedilol Therapy in Heart Failure (IMPACT-HF) trial was to evaluate treatment with carvedilol initiation predischarge compared with postdischarge initiation (>2 weeks) in stabilized patients hospitalized for heart failure.

Hypothesis:

Predischarge initiation of the beta-blocker carvedilol may improve the use of beta-blockade therapy at two months.

Study Design

Study Design:

Patients Screened: 1,887
Patients Enrolled: 363
Mean Follow Up: 60 days
Mean Patient Age: Median age 67 years
Female: 47
Mean Ejection Fraction: Median LVEF at randomization 25%

Patient Populations:

LVEF <40% and hospitalized with a primary diagnosis of heart failure

Exclusions:

Treatment with a beta-blocker within 30 days of randomization; decompensated New York Heart Association functional class IV heart failure requiring inotropic support at randomization; second- or third-degree atrioventricular block, sick sinus syndrome, or symptomatic bradycardia without a functional pacemaker; bronchial asthma or related bronchospastic conditions; symptomatic hypotension defined by the investigator; cardiogenic shock; expected survival <60 days; hypersensitivity to carvedilol; clinically manifest hepatic impairment; or being pregnant or lactating

Primary Endpoints:

Number of patients treated with beta-blockade at 60 days after randomization

Secondary Endpoints:

Number of patients discontinuing beta-blockade, median dose achieved, and a composite of death, rehospitalization, unscheduled visit for heart failure, or ≥50% increase in oral diuretic, new oral diuretic, or any intravenous therapy with diuretics, inotropes, or other vasoactive agents

Drug/Procedures Used:

Patients with stable heart failure were randomized to carvedilol initiation prehospital discharge (n=185) or to postdischarge initiation (>2 weeks) of beta-blockade at the discretion of the physician (n=178).

Concomitant Medications:

Angiotensin-converting enzyme inhibitors: 74%
Diuretic: 81%
Digoxin: 47%

Principal Findings:

Baseline characteristics were similar between groups, with a median left ventricular ejection fraction (LVEF) of 25% in each group and median time from admission to randomization of 60.9 hours. Median time to initiation of beta-blocker therapy was 17 days in the postdischarge beta-blocker initiation group.

The primary endpoint of beta-blocker use at 60 days was significantly higher in the predischarge carvedilol initiation group compared with the postdischarge initiation group (91.2% vs. 73.4%, p<0.0001). Target beta-blocker dose was achieved more frequently in the predischarge initiation group (36.3% vs. 28.6%). The frequency of permanent beta-blocker discontinuation was similar between the two groups (10.5% in the predischarge initiation group vs. 10.6% in the postdischarge group).

There was no difference in the composite endpoint between groups (45.4% in the predischarge initiation group vs. 46.1% in the postdischarge group, p=0.9) or any of the individual components of the composite. There was no increase in serious adverse events in the predischarge initiation group, with hypotension reported in 1.6% of the predischarge group versus 0.6% of the postdischarge group and bradycardia in 1.6% and 0%, respectively. The median length of hospitalization was five days in both groups.

Interpretation:

Among stabilized patients hospitalized for heart failure, initiation of beta-blocker therapy with carvedilol predischarge was associated with increased beta-blocker use at 60-day follow-up compared with initiation of beta-blocker therapy after discharge at the discretion of the physician.

The Heart Failure Society of America heart failure guidelines recommend beta-blocker use in patients with chronic heart failure and reduced systolic function, but that beta-blockers should not be routinely initiated during a hospitalization for worsening heart failure. Data from the Acute Decompensated Heart Failure (ADHERE) registry show that beta-blocker use in these patients is widely underutilized, with only 58% of eligible patients receiving the therapy at hospital discharge.

The recommendation to not initiate beta-blocker use during hospitalization for worsening heart failure is based on concern that beta-blocker therapy may worsen heart failure symptoms and short-term outcomes. However, the present data do not show an increase in adverse events in the predischarge initiation group. Additionally, a subgroup analysis of the COPERNICUS study showed no increase in worsening heart failure symptoms or adverse events.

A limitation of the present study is the open-label trial design, which may have contributed to the high treatment adherence at 60 days in both groups.

References:

Gattis WA, O'Connor CM, Gallup DS, Hasselblad V, Gheorghiade M, on behalf of the IMPACT-HF Investigators and Coordinators. Predischarge initiation of carvedilol in patients hospitalized for decompensated heart failure: results of the Initiation Management Predischarge: Process for Assessment of Carvedilol Therapy in Heart Failure (IMPACT-HF) trial. J Am Coll Cardiol 2004;43:1534-41.

Keywords: Registries, Follow-Up Studies, Carbazoles, Heart Failure, Hypotension, Stroke Volume, Bradycardia, Propanolamines


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