Background: Angiotensin-receptor blockers (ARBs) are effective treatments for patients with heart failure, but the relation between dose and clinical outcomes has not been explored. We compared the effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure.
Methods: This double-blind trial was undertaken in 255 sites in 30 countries. 3846 patients with heart failure of New York Heart Association class II-IV, left-ventricular ejection fraction 40% or less, and intolerance to angiotensin-converting-enzyme (ACE) inhibitors were randomly assigned to losartan 150 mg (n=1927) or 50 mg daily (n=1919). Allocation was by block randomisation stratified by centre and presence or absence of beta-blocker therapy, and all patients and investigators were masked to assignment. The primary endpoint was death or admission for heart failure. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00090259.
Findings: Six patients in each group were excluded because of poor data quality. With 4.7-year median follow-up in each group (IQR 3.7-5.5 for losartan 150 mg; 3.4-5.5 for losartan 50 mg), 828 (43%) patients in the 150 mg group versus 889 (46%) in the 50 mg group died or were admitted for heart failure (hazard ratio [HR] 0.90, 95% CI 0.82-0.99; p=0.027). For the two primary endpoint components, 635 patients in the 150 mg group versus 665 in the 50 mg group died (HR 0.94, 95% CI 0.84-1.04; p=0.24), and 450 versus 503 patients were admitted for heart failure (0.87, 0.76-0.98; p=0.025). Renal impairment (n=454 vs 317), hypotension (203 vs 145), and hyperkalaemia (195 vs 131) were more common in the 150 mg group than in the 50 mg group, but these adverse events did not lead to significantly more treatment discontinuations in the 150 mg group.
Interpretation: Losartan 150 mg daily reduced the rate of death or admission for heart failure in patients with heart failure, reduced left-ventricular ejection fraction, and intolerance to ACE inhibitors compared with losartan 50 mg daily. These findings show the value of up-titrating ARB doses to confer clinical benefit.
Funding: Merck (USA).
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/S0140-6736(09)61913-9 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Phase angle in bioelectrical impedance analysis for assessing congestion in acute heart failure.
PLoS One
January 2025
Cardiovascular Center, Division of Cardiology, Korea University Guro Hospital, Seoul, Republic of Korea.
Background: The phase angle (PhA) in bioelectrical impedance analysis (BIA) reflects the cell membrane integrity or body fluid equilibrium. We examined how the PhA aligns with previously known markers of acute heart failure (HF) and assessed its value as a screening tool.
Methods: PhA was measured in 50 patients with HF and 20 non-HF controls along with the edema index (EI), another BIA parameter suggestive of edema.
Permanent Left Bundle Branch Area DF-4 Defibrillator Lead Implantation-Feasibility, Procedural Caveats, Safety, and Follow-Up.
J Cardiovasc Electrophysiol
January 2025
Department of Cardiac Electrophysiology and Pacing, Arrhythmia Heart Failure Academy, The Madras Medical Mission, Chennai, Tamil Nadu, India.
Introduction: Permanent implantation of a DF-4 implantable cardiac defibrillator (ICD) lead in the left bundle branch area (LBBA-ICD) is the next paradigm in amalgamating cardiac resynchronization therapy (CRT) and defibrillation. We systematically investigated feasibility/success rate, procedural caveats, and complications associated with a permanent DF-4 LBBA ICD implant and pertinent data at short-term follow-up.
Methods: We prospectively attempted implantation of 7 Fr Durata (Abbott, Chicago, IL, USA) single coil DF-4 ICD lead at the LBBA using a fixed-curve non-deflectable CPS locator delivery sheath.
Hypertrophic heart failure promotes gut dysbiosis and gut leakage in interleukin 10-deficient mice.
Am J Physiol Heart Circ Physiol
January 2025
Department of Medicine, Division of Cardiovascular Disease, The University of Alabama at Birmingham, Birmingham, AL-35233.
Heart failure (HF) is a leading cause of death worldwide. We have shown that pressure overload (PO)-induced inflammatory cell recruitment leads to heart failure in IL-10 knockout (KO) mice. However, it's unclear if PO-induced inflammatory cells also target the gut mucosa, causing gut dysbiosis and leakage.
View Article and Find Full Text PDFCognitive impairment and limited health literacy are associated with poor health outcomes among patients with heart failure residing in rural areas.
J Rural Health
January 2025
University of Tennessee Knoxville, College of Nursing, Knoxville, Tennessee, USA.
Background: Cognitive impairment and limited health literacy are prevalent among patients with heart failure, particularly those residing in rural areas, and are linked to poor health outcomes. Little is known about the intricate relationships among cognitive function, health literacy, and rehospitalization and death in rural patients with heart failure.
Objectives: To determine the relationships among cognitive function, health literacy, and cardiac event-free survival (ie, heart failure hospitalizations and cardiac mortality) in rural patients with heart failure.
Epidemiological characteristics and risk factors for heart failure in Japanese patients with type 2 diabetes: A retrospective analysis of the J-DREAMS database.
J Diabetes Investig
January 2025
Department of Diabetes, Endocrinology and Metabolism, Center Hospital, National Center for Global Health and Medicine, Tokyo, Japan.
Aim: To determine the epidemiological characteristics and risk factors for heart failure (HF) among Japanese patients with type 2 diabetes.
Methods: A retrospective cohort analysis, using J-DREAMS database, was conducted from December 2015 to January 2020 with type 2 diabetes. The primary objectives were to describe patient characteristics stratified by HF history at baseline and new HF events during follow-up.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!