Aliskiren, Enalapril, or Aliskiren and Enalapril in Heart Failure

John J V McMurray; Henry Krum; William T Abraham; Kenneth Dickstein; Lars Valeur Køber; Akshay S Desai; Scott D Solomon; Nicola Greenlaw; M Atif Ali; Yanntong Chiang; Qing Shao; Georgia Tarnesby; Barry M Massie; ATMOSPHERE Committees Investigators

doi:10.1056/nejmoa1514859

Aliskiren, Enalapril, or Aliskiren and Enalapril in Heart Failure

John J V McMurray, Henry Krum, William T Abraham, Kenneth Dickstein, Lars Valeur Køber, Akshay S Desai, Scott D Solomon, Nicola Greenlaw, M Atif Ali, Yanntong Chiang, Qing Shao, Georgia Tarnesby, Barry M Massie, ATMOSPHERE Committees Investigators

Institut for Klinisk Medicin

141 Citationer (Scopus)

Abstract

BACKGROUND Among patients with chronic heart failure, angiotensin-converting-enzyme (ACE) inhibitors reduce mortality and hospitalization, but the role of a renin inhibitor in such patients is unknown. We compared the ACE inhibitor enalapril with the renin inhibitor aliskiren (to test superiority or at least noninferiority) and with the combination of the two treatments (to test superiority) in patients with heart failure and a reduced ejection fraction. METHODS After a single-blind run-in period, we assigned patients, in a double-blind fashion, to one of three groups: 2336 patients were assigned to receive enalapril at a dose of 5 or 10 mg twice daily, 2340 to receive aliskiren at a dose of 300 mg once daily, and 2340 to receive both treatments (combination therapy). The primary composite outcome was death from cardiovascular causes or hospitalization for heart failure. RESULTS After a median follow-up of 36.6 months, the primary outcome occurred in 770 patients (32.9%) in the combination-therapy group and in 808 (34.6%) in the enalapril group (hazard ratio, 0.93; 95% confidence interval [CI], 0.85 to 1.03). The primary outcome occurred in 791 patients (33.8%) in the aliskiren group (hazard ratio vs. enalapril, 0.99; 95% CI, 0.90 to 1.10); the prespecified test for noninferiority was not met. There was a higher risk of hypotensive symptoms in the combination-therapy group than in the enalapril group (13.8% vs. 11.0%, P = 0.005), as well as higher risks of an elevated serum creatinine level (4.1% vs. 2.7%, P = 0.009) and an elevated potassium level (17.1% vs. 12.5%, P<0.001). CONCLUSIONS In patients with chronic heart failure, the addition of aliskiren to enalapril led to more adverse events without an increase in benefit. Noninferiority was not shown for aliskiren as compared with enalapril.

Originalsprog	Engelsk
Tidsskrift	New England Journal of Medicine
Vol/bind	374
Udgave nummer	16
Sider (fra-til)	1521-1532
Antal sider	12
ISSN	0028-4793
DOI	https://doi.org/10.1056/nejmoa1514859
Status	Udgivet - 21 apr. 2016

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10.1056/nejmoa1514859

http://www.nejm.org/doi/pdf/10.1056/NEJMoa1514859

Citationsformater

McMurray, J. J. V., Krum, H., Abraham, W. T., Dickstein, K., Køber, L. V., Desai, A. S., Solomon, S. D., Greenlaw, N., Ali, M. A., Chiang, Y., Shao, Q., Tarnesby, G., Massie, B. M., & ATMOSPHERE Committees Investigators (2016). Aliskiren, Enalapril, or Aliskiren and Enalapril in Heart Failure. New England Journal of Medicine, 374(16), 1521-1532. https://doi.org/10.1056/nejmoa1514859

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title = "Aliskiren, Enalapril, or Aliskiren and Enalapril in Heart Failure",

abstract = "BACKGROUND Among patients with chronic heart failure, angiotensin-converting-enzyme (ACE) inhibitors reduce mortality and hospitalization, but the role of a renin inhibitor in such patients is unknown. We compared the ACE inhibitor enalapril with the renin inhibitor aliskiren (to test superiority or at least noninferiority) and with the combination of the two treatments (to test superiority) in patients with heart failure and a reduced ejection fraction. METHODS After a single-blind run-in period, we assigned patients, in a double-blind fashion, to one of three groups: 2336 patients were assigned to receive enalapril at a dose of 5 or 10 mg twice daily, 2340 to receive aliskiren at a dose of 300 mg once daily, and 2340 to receive both treatments (combination therapy). The primary composite outcome was death from cardiovascular causes or hospitalization for heart failure. RESULTS After a median follow-up of 36.6 months, the primary outcome occurred in 770 patients (32.9%) in the combination-therapy group and in 808 (34.6%) in the enalapril group (hazard ratio, 0.93; 95% confidence interval [CI], 0.85 to 1.03). The primary outcome occurred in 791 patients (33.8%) in the aliskiren group (hazard ratio vs. enalapril, 0.99; 95% CI, 0.90 to 1.10); the prespecified test for noninferiority was not met. There was a higher risk of hypotensive symptoms in the combination-therapy group than in the enalapril group (13.8% vs. 11.0%, P = 0.005), as well as higher risks of an elevated serum creatinine level (4.1% vs. 2.7%, P = 0.009) and an elevated potassium level (17.1% vs. 12.5%, P<0.001). CONCLUSIONS In patients with chronic heart failure, the addition of aliskiren to enalapril led to more adverse events without an increase in benefit. Noninferiority was not shown for aliskiren as compared with enalapril.",

keywords = "Aged, Amides, Angiotensin-Converting Enzyme Inhibitors, Chronic Disease, Diabetes Mellitus, Type 2, Double-Blind Method, Drug Therapy, Combination, Enalapril, Female, Follow-Up Studies, Fumarates, Heart Failure, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Renin, Stroke Volume, Treatment Failure, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't",

author = "McMurray, {John J V} and Henry Krum and Abraham, {William T} and Kenneth Dickstein and K{\o}ber, {Lars Valeur} and Desai, {Akshay S} and Solomon, {Scott D} and Nicola Greenlaw and Ali, {M Atif} and Yanntong Chiang and Qing Shao and Georgia Tarnesby and Massie, {Barry M} and {ATMOSPHERE Committees Investigators}",

year = "2016",

month = apr,

day = "21",

doi = "10.1056/nejmoa1514859",

language = "English",

volume = "374",

pages = "1521--1532",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachusetts Medical Society",

number = "16",

}

TY - JOUR

T1 - Aliskiren, Enalapril, or Aliskiren and Enalapril in Heart Failure

AU - McMurray, John J V

AU - Krum, Henry

AU - Abraham, William T

AU - Dickstein, Kenneth

AU - Køber, Lars Valeur

AU - Desai, Akshay S

AU - Solomon, Scott D

AU - Greenlaw, Nicola

AU - Ali, M Atif

AU - Chiang, Yanntong

AU - Shao, Qing

AU - Tarnesby, Georgia

AU - Massie, Barry M

AU - ATMOSPHERE Committees Investigators

PY - 2016/4/21

Y1 - 2016/4/21

N2 - BACKGROUND Among patients with chronic heart failure, angiotensin-converting-enzyme (ACE) inhibitors reduce mortality and hospitalization, but the role of a renin inhibitor in such patients is unknown. We compared the ACE inhibitor enalapril with the renin inhibitor aliskiren (to test superiority or at least noninferiority) and with the combination of the two treatments (to test superiority) in patients with heart failure and a reduced ejection fraction. METHODS After a single-blind run-in period, we assigned patients, in a double-blind fashion, to one of three groups: 2336 patients were assigned to receive enalapril at a dose of 5 or 10 mg twice daily, 2340 to receive aliskiren at a dose of 300 mg once daily, and 2340 to receive both treatments (combination therapy). The primary composite outcome was death from cardiovascular causes or hospitalization for heart failure. RESULTS After a median follow-up of 36.6 months, the primary outcome occurred in 770 patients (32.9%) in the combination-therapy group and in 808 (34.6%) in the enalapril group (hazard ratio, 0.93; 95% confidence interval [CI], 0.85 to 1.03). The primary outcome occurred in 791 patients (33.8%) in the aliskiren group (hazard ratio vs. enalapril, 0.99; 95% CI, 0.90 to 1.10); the prespecified test for noninferiority was not met. There was a higher risk of hypotensive symptoms in the combination-therapy group than in the enalapril group (13.8% vs. 11.0%, P = 0.005), as well as higher risks of an elevated serum creatinine level (4.1% vs. 2.7%, P = 0.009) and an elevated potassium level (17.1% vs. 12.5%, P<0.001). CONCLUSIONS In patients with chronic heart failure, the addition of aliskiren to enalapril led to more adverse events without an increase in benefit. Noninferiority was not shown for aliskiren as compared with enalapril.

AB - BACKGROUND Among patients with chronic heart failure, angiotensin-converting-enzyme (ACE) inhibitors reduce mortality and hospitalization, but the role of a renin inhibitor in such patients is unknown. We compared the ACE inhibitor enalapril with the renin inhibitor aliskiren (to test superiority or at least noninferiority) and with the combination of the two treatments (to test superiority) in patients with heart failure and a reduced ejection fraction. METHODS After a single-blind run-in period, we assigned patients, in a double-blind fashion, to one of three groups: 2336 patients were assigned to receive enalapril at a dose of 5 or 10 mg twice daily, 2340 to receive aliskiren at a dose of 300 mg once daily, and 2340 to receive both treatments (combination therapy). The primary composite outcome was death from cardiovascular causes or hospitalization for heart failure. RESULTS After a median follow-up of 36.6 months, the primary outcome occurred in 770 patients (32.9%) in the combination-therapy group and in 808 (34.6%) in the enalapril group (hazard ratio, 0.93; 95% confidence interval [CI], 0.85 to 1.03). The primary outcome occurred in 791 patients (33.8%) in the aliskiren group (hazard ratio vs. enalapril, 0.99; 95% CI, 0.90 to 1.10); the prespecified test for noninferiority was not met. There was a higher risk of hypotensive symptoms in the combination-therapy group than in the enalapril group (13.8% vs. 11.0%, P = 0.005), as well as higher risks of an elevated serum creatinine level (4.1% vs. 2.7%, P = 0.009) and an elevated potassium level (17.1% vs. 12.5%, P<0.001). CONCLUSIONS In patients with chronic heart failure, the addition of aliskiren to enalapril led to more adverse events without an increase in benefit. Noninferiority was not shown for aliskiren as compared with enalapril.

KW - Aged

KW - Amides

KW - Angiotensin-Converting Enzyme Inhibitors

KW - Chronic Disease

KW - Diabetes Mellitus, Type 2

KW - Double-Blind Method

KW - Drug Therapy, Combination

KW - Enalapril

KW - Female

KW - Follow-Up Studies

KW - Fumarates

KW - Heart Failure

KW - Humans

KW - Kaplan-Meier Estimate

KW - Male

KW - Middle Aged

KW - Renin

KW - Stroke Volume

KW - Treatment Failure

KW - Comparative Study

KW - Journal Article

KW - Multicenter Study

KW - Randomized Controlled Trial

KW - Research Support, Non-U.S. Gov't

U2 - 10.1056/nejmoa1514859

DO - 10.1056/nejmoa1514859

M3 - Journal article

C2 - 27043774

SN - 0028-4793

VL - 374

SP - 1521

EP - 1532

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 16

ER -

Aliskiren, Enalapril, or Aliskiren and Enalapril in Heart Failure

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