Effect of ularitide on cardiovascular mortality in acute heart failure

M. Packer, C. O'Connor, J. J.V. McMurray, J. Wittes, W. T. Abraham, S. D. Anker, K. Dickstein, G. Filippatos, R. Holcomb, H. Krum, A. P. Maggioni, A. Mebazaa, W. F. Peacock, M. C. Petrie, P. Ponikowski, F. Ruschitzka, D. J. Van Veldhuisen, L. S. Kowarski, M. Schactman, J. HolzmeisterTRUE-AHF Investigators

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: In patients with acute heart failure, early intervention with an intravenous vasodilator has been proposed as a therapeutic goal to reduce cardiac-wall stress and, potentially, myocardial injury, thereby favorably affecting patients' long-term prognosis. METHODS: In this double-blind trial, we randomly assigned 2157 patients with acute heart failure to receive a continuous intravenous infusion of either ularitide at a dose of 15 ng per kilogram of body weight per minute or matching placebo for 48 hours, in addition to accepted therapy. Treatment was initiated a median of 6 hours after the initial clinical evaluation. The coprimary outcomes were death from cardiovascular causes during a median follow-up of 15 months and a hierarchical composite end point that evaluated the initial 48-hour clinical course. RESULTS: Death from cardiovascular causes occurred in 236 patients in the ularitide group and 225 patients in the placebo group (21.7% vs. 21.0%; hazard ratio, 1.03; 96% confidence interval, 0.85 to 1.25; P=0.75). In the intention-to-treat analysis, there was no significant between-group difference with respect to the hierarchical composite outcome. The ularitide group had greater reductions in systolic blood pressure and in levels of N-terminal pro-brain natriuretic peptide than the placebo group. However, changes in cardiac troponin T levels during the infusion did not differ between the two groups in the 55% of patients with paired data. CONCLUSIONS: In patients with acute heart failure, ularitide exerted favorable physiological effects (without affecting cardiac troponin levels), but short-term treatment did not affect a clinical composite end point or reduce long-term cardiovascular mortality.

Original languageEnglish (US)
Pages (from-to)1956-1964
Number of pages9
JournalNew England Journal of Medicine
Volume376
Issue number20
DOIs
StatePublished - May 18 2017

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Heart Failure
Mortality
Placebos
Cause of Death
Blood Pressure
Troponin T
Intention to Treat Analysis
Troponin
Brain Natriuretic Peptide
Therapeutics
Ularitide
Vasodilator Agents
Intravenous Infusions
Body Weight
Confidence Intervals
Wounds and Injuries

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Packer, M., O'Connor, C., McMurray, J. J. V., Wittes, J., Abraham, W. T., Anker, S. D., ... TRUE-AHF Investigators (2017). Effect of ularitide on cardiovascular mortality in acute heart failure. New England Journal of Medicine, 376(20), 1956-1964. https://doi.org/10.1056/NEJMoa1601895

Effect of ularitide on cardiovascular mortality in acute heart failure. / Packer, M.; O'Connor, C.; McMurray, J. J.V.; Wittes, J.; Abraham, W. T.; Anker, S. D.; Dickstein, K.; Filippatos, G.; Holcomb, R.; Krum, H.; Maggioni, A. P.; Mebazaa, A.; Peacock, W. F.; Petrie, M. C.; Ponikowski, P.; Ruschitzka, F.; Van Veldhuisen, D. J.; Kowarski, L. S.; Schactman, M.; Holzmeister, J.; TRUE-AHF Investigators.

In: New England Journal of Medicine, Vol. 376, No. 20, 18.05.2017, p. 1956-1964.

Research output: Contribution to journalArticle

Packer, M, O'Connor, C, McMurray, JJV, Wittes, J, Abraham, WT, Anker, SD, Dickstein, K, Filippatos, G, Holcomb, R, Krum, H, Maggioni, AP, Mebazaa, A, Peacock, WF, Petrie, MC, Ponikowski, P, Ruschitzka, F, Van Veldhuisen, DJ, Kowarski, LS, Schactman, M, Holzmeister, J & TRUE-AHF Investigators 2017, 'Effect of ularitide on cardiovascular mortality in acute heart failure', New England Journal of Medicine, vol. 376, no. 20, pp. 1956-1964. https://doi.org/10.1056/NEJMoa1601895
Packer M, O'Connor C, McMurray JJV, Wittes J, Abraham WT, Anker SD et al. Effect of ularitide on cardiovascular mortality in acute heart failure. New England Journal of Medicine. 2017 May 18;376(20):1956-1964. https://doi.org/10.1056/NEJMoa1601895
Packer, M. ; O'Connor, C. ; McMurray, J. J.V. ; Wittes, J. ; Abraham, W. T. ; Anker, S. D. ; Dickstein, K. ; Filippatos, G. ; Holcomb, R. ; Krum, H. ; Maggioni, A. P. ; Mebazaa, A. ; Peacock, W. F. ; Petrie, M. C. ; Ponikowski, P. ; Ruschitzka, F. ; Van Veldhuisen, D. J. ; Kowarski, L. S. ; Schactman, M. ; Holzmeister, J. ; TRUE-AHF Investigators. / Effect of ularitide on cardiovascular mortality in acute heart failure. In: New England Journal of Medicine. 2017 ; Vol. 376, No. 20. pp. 1956-1964.
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abstract = "BACKGROUND: In patients with acute heart failure, early intervention with an intravenous vasodilator has been proposed as a therapeutic goal to reduce cardiac-wall stress and, potentially, myocardial injury, thereby favorably affecting patients' long-term prognosis. METHODS: In this double-blind trial, we randomly assigned 2157 patients with acute heart failure to receive a continuous intravenous infusion of either ularitide at a dose of 15 ng per kilogram of body weight per minute or matching placebo for 48 hours, in addition to accepted therapy. Treatment was initiated a median of 6 hours after the initial clinical evaluation. The coprimary outcomes were death from cardiovascular causes during a median follow-up of 15 months and a hierarchical composite end point that evaluated the initial 48-hour clinical course. RESULTS: Death from cardiovascular causes occurred in 236 patients in the ularitide group and 225 patients in the placebo group (21.7{\%} vs. 21.0{\%}; hazard ratio, 1.03; 96{\%} confidence interval, 0.85 to 1.25; P=0.75). In the intention-to-treat analysis, there was no significant between-group difference with respect to the hierarchical composite outcome. The ularitide group had greater reductions in systolic blood pressure and in levels of N-terminal pro-brain natriuretic peptide than the placebo group. However, changes in cardiac troponin T levels during the infusion did not differ between the two groups in the 55{\%} of patients with paired data. CONCLUSIONS: In patients with acute heart failure, ularitide exerted favorable physiological effects (without affecting cardiac troponin levels), but short-term treatment did not affect a clinical composite end point or reduce long-term cardiovascular mortality.",
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AU - Packer, M.

AU - O'Connor, C.

AU - McMurray, J. J.V.

AU - Wittes, J.

AU - Abraham, W. T.

AU - Anker, S. D.

AU - Dickstein, K.

AU - Filippatos, G.

AU - Holcomb, R.

AU - Krum, H.

AU - Maggioni, A. P.

AU - Mebazaa, A.

AU - Peacock, W. F.

AU - Petrie, M. C.

AU - Ponikowski, P.

AU - Ruschitzka, F.

AU - Van Veldhuisen, D. J.

AU - Kowarski, L. S.

AU - Schactman, M.

AU - Holzmeister, J.

AU - TRUE-AHF Investigators

PY - 2017/5/18

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N2 - BACKGROUND: In patients with acute heart failure, early intervention with an intravenous vasodilator has been proposed as a therapeutic goal to reduce cardiac-wall stress and, potentially, myocardial injury, thereby favorably affecting patients' long-term prognosis. METHODS: In this double-blind trial, we randomly assigned 2157 patients with acute heart failure to receive a continuous intravenous infusion of either ularitide at a dose of 15 ng per kilogram of body weight per minute or matching placebo for 48 hours, in addition to accepted therapy. Treatment was initiated a median of 6 hours after the initial clinical evaluation. The coprimary outcomes were death from cardiovascular causes during a median follow-up of 15 months and a hierarchical composite end point that evaluated the initial 48-hour clinical course. RESULTS: Death from cardiovascular causes occurred in 236 patients in the ularitide group and 225 patients in the placebo group (21.7% vs. 21.0%; hazard ratio, 1.03; 96% confidence interval, 0.85 to 1.25; P=0.75). In the intention-to-treat analysis, there was no significant between-group difference with respect to the hierarchical composite outcome. The ularitide group had greater reductions in systolic blood pressure and in levels of N-terminal pro-brain natriuretic peptide than the placebo group. However, changes in cardiac troponin T levels during the infusion did not differ between the two groups in the 55% of patients with paired data. CONCLUSIONS: In patients with acute heart failure, ularitide exerted favorable physiological effects (without affecting cardiac troponin levels), but short-term treatment did not affect a clinical composite end point or reduce long-term cardiovascular mortality.

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