The safety of intravenous diuretics alone versus diuretics plus parenteral vasoactive therapies in hospitalized patients with acutely decompensated heart failure: A propensity score and instrumental variable analysis using the Acutely Decompensated Heart Failure National Registry (ADHERE) database

Received 30 October 2006; accepted 16 April 2007. published online 04 June 2007.

Background

The treatment of acute decompensated heart failure remains problematic and most often requires parenteral therapies. Significant concerns have been expressed regarding risks and benefits of individual therapies, especially nesiritide (NES), but few studies have compared the relative safety of varied intravenous therapies on clinical outcomes.

Methods

We compared the safety of intravenous diuretics (DIUR), inotropes (INO), and vasodilators (nitroglycerin [NTG]) on mortality rates and worsening renal function in 99963 inpatients with acutely decompensated heart failure (ADHF). Patients with a diagnosis of ADHF within 48 hours were grouped by intended primary treatment (intravenous agents administered during the first 2 hours of intravenous therapy). Treatments studied were (a) intended monotherapy (DIUR), (b) intended combination therapy (DIUR + NES, NTG, or INO), and (c) sequential therapy (intended DIUR monotherapy followed by a second agent administered >2 hours later). Propensity-matched cohorts and instrumental analysis were used to adjust for differences among patients in treatment groups.

Results

Intended DIUR monotherapy yielded an unadjusted inpatient mortality rate of 3.2%. After intended DIUR monotherapy, inpatient mortality was not higher for sequential use of NES than for sequential use of NTG (3.4% vs 6.2%, P = .0028). In all regimens, INOs were associated with higher inpatient mortality than were diuretics or vasodilators used alone. The rate of worsening renal function was higher with combination of diuretic-based regimens with NES (risk ratio 1.44, P < .0001) or NTG (RR 1.2, P = .012) compared with diuretics alone.

Conclusions

Compared with alternative intravenous regimens, administration of vasodilators, including NES, was not associated with increased inpatient mortality. A large randomized controlled clinical trial is being planned to prospectively address the question of risks and benefits of NES for ADHF.

a Midwest Heart Foundation, Lombard, IL

b Cardinal Health Clinical Research Group, Marlborough, MA

c Brigham and Women's Hospital, Harvard Medical School, Boston, MA

d Michael Pine and Associates, Inc, Chicago, IL

e The University of Chicago, Chicago, IL

f Pharmaceutical Economics and Policy, University of Southern California School of Pharmacy, Los Angeles, CA

g Baylor Heart and Vascular Institute, Dallas, TX

h Ahmanson-UCLA Cardiomyopathy Center, University of California, Los Angeles, Los Angeles, CA

Reprint requests: Maria Rosa Costanzo, MD, FACC, Edward Hospital Center for Advanced Heart Failure, Midwest Heart Specialists, 801 South Washington Street, PO Box 3226, Naperville, IL 60566.

Dr Costanzo, Dr Saltzberg, Dr Yancy, and Dr Fonarow have received honoraria and have served as consultants for Scios Inc. Dr Gupta has received honoraria from Scios Inc, Mountain View, CA. Dr Hay has served as a consultant to Scios Inc. The Acutely Decompensated Heart Failure National Registry (ADHERE) and this study were funded by Scios Inc. Access to the ADHERE database was provided by the Scientific Advisory Committee for ADHERE. The investigators designed and executed the analysis and prepared this manuscript independent of the sponsor, Scios Inc. The sponsor reviewed the results of the analysis and the manuscript. However, neither results nor manuscript were altered as a consequence of the sponsor's review.

Dr Costanzo had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The study concept and design were by Costanzo, Johannes, Pine, Gupta, Hay, Fonarow, and Yancy. Acquisition of data was done by Johannes, Pine, and Gupta; analysis and interpretation of data by Costanzo, Johannes, Pine, Gupta, Saltzberg, Hay, Yancy, and Fonarow; drafting of the manuscript by Costanzo, Johannes, Pine, and Gupta; critical revision of the manuscript for important intellectual content by Costanzo, Johannes, Pine, Gupta, Saltzberg, Hay, Yancy, and Fonarow. Statistical expertise was provided by Johannes, Pine, and Hay; funding obtained by Johannes and Gupta; and administrative, technical, or material support obtained by Johannes, Pine, Gupta, and Hay. Study supervision was done by Johannes, Pine, and Gupta.

PII: S0002-8703(07)00357-2

doi:10.1016/j.ahj.2007.04.033

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