Effect of nesiritide in patients with acute decompensated heart failure

Christopher O'Connor, Randall Starling, Adrian Hernandez, Paul Armstrong, Kenneth Dickstein, Vic Hasselblad, Gretchen Heizer, Michel Komajda, Barry Massie, John McMurray, Markku Nieminen, Craig Reist, Jean-Lucien Rouleau, Karl Swedberg, Kirkwood Adams, Stefan Anker, Dan Atar, Alexander Battler, Rodrigo Botero, Norman BohidarJaved Butler, Nadine Clausell, Ramon Corbalan, Maria Costanzo, Ulf Dahlstrom, Lawrence Deckelbaum, Raffael Diaz, Mark Dunlap, Justin Ezekowitz, David Feldman, G Felker, Gregg Fonarow, Daniel Gennevois, Stephen Gottlieb, James Hill, Judd Hollander, Jonathon Howlett, Michael Hudson, Robb Kociol, Henry Krum, Aleksandras Laucevicius, Wayne Levy, Gustavo Mendez, Marco Metra, Sanjay Mittal, Byung-Hee Oh, Naveen Pereira, Piotr Ponikowski, W Wilson Tang, Supachai Tanomsup, John Teerlink, Filippos Triposkiadis, Richard Troughton, Adriaan Voors, David Whellan, Faiez Zannad, Robert Califf

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Abstract

Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. Methods We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. Results Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5 vs. 42.1 , P = 0.03) and 24 hours (68.2 vs. 66.1 , P = 0.007), but the prespecified level for significance (Pa??0.005 for both assessments or Pa??0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4 in the nesiritide group versus 10.1 in the placebo group (absolute difference, a??0.7 percentage points; 95 confidence interval [CI], a??2.1 to 0.7; P = 0.31). There were no significant differences in rates of death from any cause at 30 days (3.6 with nesiritide vs. 4.0 with placebo; absolute difference, a??0.4 percentage points; 95 CI, a??1.3 to 0.5) or rates of worsening renal function, defined by more than a 25 decrease in the estimated glomerular filtration rate (31.4 vs. 29.5 ; odds ratio, 1.09; 95 CI, 0.98 to 1.21; P = 0.11). Conclusions Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis
Original languageEnglish
Pages (from-to)32 - 43
Number of pages12
JournalThe New England Journal of Medicine
Volume365
Issue number1
DOIs
Publication statusPublished - 2011

Cite this

O'Connor, C., Starling, R., Hernandez, A., Armstrong, P., Dickstein, K., Hasselblad, V., Heizer, G., Komajda, M., Massie, B., McMurray, J., Nieminen, M., Reist, C., Rouleau, J-L., Swedberg, K., Adams, K., Anker, S., Atar, D., Battler, A., Botero, R., ... Califf, R. (2011). Effect of nesiritide in patients with acute decompensated heart failure. The New England Journal of Medicine, 365(1), 32 - 43. https://doi.org/10.1056/NEJMoa1100171