warfarin and Heart-Failure--Systolic

Heart failure is an independent risk factor for stroke. Anticoagulation is effective for prevention of cardio-embolic stroke secondary to atrial fibrillation or mechanical heart valves but is of uncertain benefit in heart failure patients. We performed this meta-analysis to obtain the best estimates of the efficacy and safety of warfarin as compared with antiplatelet therapy in patients with systolic heart failure who are in sinus rhythm.. A systematic search was performed using PubMed and Central Register of Controlled Trials databases for all randomized controlled trials, which compare warfarin with antiplatelet therapy given for at least one-month in heart failure patients with sinus rhythm and report at least one of the following outcomes: ischemic stroke, death, myocardial infarction, hospitalization due to worsening heart failure, intracranial hemorrhage, and major hemorrhage. Four randomized controlled trials involving adjusted-dose warfarin (4187 subjects) were included. When compared with antiplatelet therapy, warfarin reduced ischemic stroke by 0·74% per year (RR 0·49; 95% CI: 0·32-0·73: P = 0·0006; Number needed to treat = 135) but increased major hemorrhage by 0·99% per year (RR 2·15; 95% CI: 1·55-2·99: P < 0·00001; Number needed to harm = 101). Warfarin did not significantly affect the risk of death, myocardial infarction, hospitalization due to heart failure or intracranial hemorrhage as compared with antiplatelet therapy.. Warfarin as compared with antiplatelet therapy reduces risk of ischemic stroke, does not significantly affect death, myocardial infarction, hospitalization due to heart failure or intracranial hemorrhage and increases major hemorrhage in heart failure patients who are in sinus rhythm.

Topics: Anticoagulants; Heart Failure, Systolic; Heart Rate; Humans; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Warfarin

Systolic heart failure is a common syndrome whose incidence is expected to increase. Several treatment modalities, such as beta-blockers and angiotensin-converting enzyme inhibitors, improve survival. Whether antithrombotic treatment is effective remains to be elucidated, although observations suggest a prothrombotic state in heart failure. This article focuses on this prothrombotic state and discusses the risk of thromboembolic events, pathophysiological mechanisms, and the potential role of anticoagulant treatment.

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Aspirin; Fibrinolytic Agents; Heart Failure, Systolic; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Prognosis; Pulmonary Embolism; Randomized Controlled Trials as Topic; Renin-Angiotensin System; Thromboembolism; Warfarin

Left atrium (LA) dilation is associated with adverse cardiovascular (CV) outcomes. Blood stasis, thrombus formation and atrial fibrillation may occur, especially in heart failure (HF) patients. It is not known whether preventive antithrombotic treatment may decrease the incidence of CV events in HF patients with LA enlargement. We investigated the relationship between LA enlargement and CV outcomes in HF patients and the effect of different antithrombotic treatments.. Two-dimensional echocardiography with LA volume index (LAVi) measurement was performed in 1148 patients with systolic HF from the Warfarin versus Aspirin in Reduced Ejection Fraction (WARCEF) trial. Patients were randomized to warfarin or aspirin and followed for 3.4 ± 1.7 years. While the primary aim of the trial was a composite of ischaemic stroke, death, and intracerebral haemorrhage, the present report focuses on the individual CV events, whose incidence was compared across different LAVi and treatment subgroups. After adjustment for demographics and clinical covariates, moderate or severe LA enlargement was significantly associated with total death (hazard ratio 1.6 and 2.7, respectively), CV death (HR 1.7 and 3.3), and HF hospitalization (HR 2.3 and 2.6) but not myocardial infarction (HR 1.0 and 1.4) or ischaemic stroke (1.1 and 1.5). The increased risk was observed in both patients treated with warfarin or aspirin. In warfarin-treated patients, a time in therapeutic range >60% was associated with lower event rates, and an interaction between LAVi and time in therapeutic range was observed for death (P = 0.034).. In patients with systolic HF, moderate or severe LA enlargement is associated with death and HF hospitalization despite treatment with antithrombotic medications. The possibility that achieving a more consistent therapeutic level of anticoagulation may decrease the risk of death requires further investigation.

Topics: Anticoagulants; Argentina; Aspirin; Canada; Cardiac Volume; Dose-Response Relationship, Drug; Echocardiography; Female; Heart Atria; Heart Failure, Systolic; Humans; Incidence; Male; Middle Aged; Platelet Aggregation Inhibitors; Stroke Volume; Survival Rate; Thromboembolism; Treatment Outcome; United States; Warfarin

Patients with systolic heart failure (HF) are at increased risk of both ischemic stroke and death. Currently, no risk scores are available to identify HF patients at high risk of stroke or death. The Warfarin vs. Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial studied 2305 HF patients, in sinus rhythm, followed for up to 6 years (3.5±1.5 years). This trial showed no overall difference in those treated with warfarin vs aspirin with regard to death or stroke. The present study develops the first prognostic model to identify patients at higher risk of stroke or death based on their overall risk profile.. A scoring algorithm using 8 readily obtainable clinical characteristics as predictors, age, gender, hemoglobin, blood urea nitrogen, ejection fraction, diastolic blood pressure, diabetes status, and prior stroke or transient ischemic attack (C-index=0.65, 95% CI: 0.613-0.681), was developed. It was validated internally using a bootstrap method. In predicting 1-year survival for death alone, our 8-predictor model had an AUC of 0.63 (95% CI: 0.579-0.678) while the 14-predictor Seattle model had an AUC of 0.72. The Seattle model did not report stroke.. This novel prognostic model predicts the overall risk of ischemic stroke or death for HF patients. This model compares favorably for death with the Seattle model and has the added utility of including stroke as an endpoint. Use of this model will help identify those patients in need of more intensive monitoring and therapy and may help identify appropriate populations for trials of new therapies.. http://www.Clinicatrials.govNCT00041938.

Topics: Aged; Algorithms; Anticoagulants; Area Under Curve; Aspirin; Cause of Death; Double-Blind Method; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Models, Statistical; Prognosis; Risk Assessment; Risk Factors; Stroke; Warfarin

We sought to determine whether cognitive function in stable outpatients with heart failure (HF) is affected by HF severity. A retrospective, cross-sectional analysis was performed using data from 2, 043 outpatients with systolic HF and without prior stroke enrolled in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial. Multivariable regression analysis was used to assess the relationship between cognitive function measured using the Mini-Mental Status Exam (MMSE) and markers of HF severity (left ventricular ejection fraction [LVEF], New York Heart Association [NYHA] functional class, and 6-minute walk distance). The mean (SD) for the MMSE was 28.6 (2.0), with 64 (3.1%) of the 2,043 patients meeting the cut-off of MMSE <24 that indicates need for further evaluation of cognitive impairment. After adjustment for demographic and clinical covariates, 6-minute walk distance (β-coefficient 0.002, p<0.0001), but not LVEF or NYHA functional class, was independently associated with the MMSE as a continuous measure. Age, education, smoking status, body mass index, and hemoglobin level were also independently associated with the MMSE. In conclusion, six-minute walk distance, but not LVEF or NYHA functional class, was an important predictor of cognitive function in ambulatory patients with systolic heart failure.

Topics: Age Factors; Aged; Aspirin; Body Mass Index; Cognition; Cross-Sectional Studies; Educational Status; Exercise Tolerance; Female; Fibrinolytic Agents; Heart Failure, Systolic; Humans; Male; Middle Aged; Multivariate Analysis; Outpatients; Retrospective Studies; Severity of Illness Index; Smoking; Stroke Volume; Ventricular Function, Left; Walking; Warfarin

This study aimed to investigate the impact of baseline 6 min walk test distance (6MWTD) on time to major cardiovascular (CV) events in heart failure with reduced ejection fraction (HFrEF) and its impact in clinically relevant subgroups.. In the WARCEF (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction) trial, 6MWTD at baseline was available in 2102 HFrEF patients. Median follow-up was 3.4 years. All-cause death and heart failure hospitalization (HFH) exhibited a significant non-linear relationship with 6MWTD (P = 0.023 and 0.032, respectively), whereas a significant association between 6MWTD and CV death was shown in a linear model [hazard ratio (HR) per 10 m increase, 0.989; P = 0.011]. In linear splines with the best cut-off point at 200 m, the positive effect of a longer 6MWTD on all-cause death and HFH was only observed for 6MWTD > 200 m (HR per 10 m increase, 0.987; P = 0.0036 and 0.986; P = 0.0022, respectively). The associations between 6MWTD and CV outcomes were consistent across clinical subgroups; for age, a significant relationship between 6MWTD and HFH was observed in patients ≥60 years (HR per 10 m increase, 0.98; P < 0.001), but not in patients <60 years (HR per 10 m increase, 1.00; P = 0.98; P = 0.02 for the interaction).. In HFrEF, 6MWTD is independently associated with all-cause death, CV death, and HFH. 6MWTD of 200 m is the best cut-off point for predicting these adverse events. The prognostic impact of 6MWTD for HFH was only observed in older patients.

Topics: Aged; Child; Heart Failure, Systolic; Humans; Prognosis; Stroke Volume; Walk Test; Warfarin

This study sought to characterize cognitive decline (CD) over time and its predictors in patients with systolic heart failure (HF).. Despite the high prevalence of CD and its impact on mortality, predictors of CD in HF have not been established.. This study investigated CD in the WARCEF (Warfarin versus Aspirin in Reduced Ejection Fraction) trial, which performed yearly Mini-Mental State Examinations (MMSE) (higher scores indicate better cognitive function; e.g., normal score: 24 or higher). A longitudinal time-varying analysis was performed among pertinent covariates, including baseline MMSE and MMSE scores during follow-up, analyzed both as a continuous variable and a 2-point decrease. To account for a loss to follow-up, data at the baseline and at the 12-month visit were analyzed separately (sensitivity analysis).. A total of 1,846 patients were included. In linear regression, MMSE decrease was independently associated with higher baseline MMSE score (p < 0.0001), older age (p < 0.0001), nonwhite race/ethnicity (p < 0.0001), and lower education (p < 0.0001). In logistic regression, CD was independently associated with higher baseline MMSE scores (odds ratio [OR]: 1.13; 95% confidence interval [CI]: 1.07 to 1.20]; p < 0.001), older age (OR: 1.37; 95% CI: 1.24 to 1.50; p < 0.001), nonwhite race/ethnicity (OR: 2.32; 95% CI: 1.72 to 3.13 for black; OR: 1.94; 95% CI: 1.40 to 2.69 for Hispanic vs. white; p < 0.001), lower education (p < 0.001), and New York Heart Association functional class II or higher (p = 0.03). Warfarin and other medications were not associated with CD. Similar trends were seen in the sensitivity analysis (n = 1,439).. CD in HF is predicted by baseline cognitive status, demographic variables, and NYHA functional class. The possibility of intervening on some of its predictors suggests the need for the frequent assessment of cognitive function in patients with HF. (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction [WARCEF]; NCT00041938).

Topics: Aged; Anticoagulants; Aspirin; Cognitive Dysfunction; Female; Fibrinolytic Agents; Heart Failure, Systolic; Humans; Male; Middle Aged; Retrospective Studies; Stroke Volume; Time Factors; Warfarin

Topics: Fatal Outcome; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Myocardial Infarction; Pancreatic Neoplasms; Physician-Patient Relations; Urinary Tract Infections; Venous Thrombosis; Warfarin

Warfarin is often used in patients with systolic heart failure (HF) to prevent adverse outcomes. However, its long-term effect remains controversial. The objective of this study was to determine the association of warfarin use and outcomes in patients with advanced chronic systolic HF without atrial fibrillation (AF), previous thromboembolic events, or prosthetic valves. Of the 2,708 BEST patients, 1,642 were free of AF without a history of thromboembolic events and without prosthetic valves at baseline. Of these, 471 patients (29%) were receiving warfarin. Propensity scores for warfarin use were estimated for each patient and were used to assemble a matched cohort of 354 pairs of patients with and without warfarin use who were balanced on 62 baseline characteristics. Kaplan-Meier and Cox regression analyses were used to estimate the association between warfarin use and outcomes during 4.5 years of follow-up. Matched participants had a mean age ± SD of 57 ± 13 years with 24% women and 24% African-Americans. All-cause mortality occurred in 30% of matched patients in the 2 groups receiving and not receiving warfarin (hazard ratio 0.86, 95% confidence interval 0.62 to 1.19, p = 0.361). Warfarin use was not associated with cardiovascular mortality (hazard ratio 0.97, 95% confidence interval 0.68 to 1.38, p = 0.855), or HF hospitalization (hazard ratio 1.09, 95% confidence interval 0.82 to 1.44, p = 0.568). In conclusion, in patients with chronic advanced systolic HF without AF or other recommended indications for anticoagulation, prevalence of warfarin use was high. However, despite a therapeutic international normalized ratio in those receiving warfarin, its use had no significant intrinsic association with mortality and hospitalization.

Topics: Adult; Algorithms; Anticoagulants; Atrial Fibrillation; Case-Control Studies; Chronic Disease; Confidence Intervals; Female; Follow-Up Studies; Heart Failure, Systolic; Heart Valve Prosthesis; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Proportional Hazards Models; Regression Analysis; Thromboembolism; Treatment Outcome; Warfarin