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 language | English (US) |
|---|---|
| Pages (from-to) | 1956-1964 |
| Number of pages | 9 |
| Journal | New England Journal of Medicine |
| Volume | 376 |
| Issue number | 20 |
| DOIs | |
| State | Published - May 18 2017 |
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ASJC Scopus subject areas
- Medicine(all)
Cite this
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 journal › Article
}
TY - JOUR
T1 - Effect of ularitide on cardiovascular mortality in acute heart failure
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
Y1 - 2017/5/18
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.
AB - 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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U2 - 10.1056/NEJMoa1601895
DO - 10.1056/NEJMoa1601895
M3 - Article
C2 - 28402745
AN - SCOPUS:85019818217
VL - 376
SP - 1956
EP - 1964
JO - New England Journal of Medicine
JF - New England Journal of Medicine
SN - 0028-4793
IS - 20
ER -