Heart Failure Site-Based Research in the United States: Results of the Heart Failure Society of America Research Network Survey.

OBJECTIVES: This study sought to determine clinician and scientist involvement in heart failure (HF) clinical research and to describe the challenges of conducting clinical trials in the United States. BACKGROUND: Improvements in the current capability, potential, and deficiencies of the HF clinical research infrastructure in the United States are needed in order to enhance efficiency and impact. METHODS: The Heart Failure Society of America (HFSA) distributed an electronic survey regarding HF clinical trial activity for the purpose of understanding the barriers that exist to conducting high-quality HF clinical research. RESULTS: Overall, 1,794 HFSA members were queried, and 434 members (24%) completed surveys, whereas a total of 7,589 individuals with interest in HF were queried, and 615 completed surveys. Of the respondents, 410 (67%) were actively engaged in HF research and 120 (20%) were interested in research. Most respondents, 270, were physicians (44%); 311 of the total (76% of the total and 80% of physicians) practiced in academic institutions; 333 respondents (81%) had served as principal investigators and 73 (18%) as site coordinators. Respondents active in clinical research usually participated in 1 to 5 trials and enrolled 1 to 20 patients annually. Institutional review board (IRB) approval typically required 3 months, and contract completion required 3 to 6 months per site. The greatest barriers to research were insufficient site budgets, delay in contracting, inability to find participants meeting trial entry criteria, and unavailability of qualified study coordinators. CONCLUSIONS: Many U.S. clinical research sites are constrained by budgetary, staffing, and contractual issues. The HFSA Research Network seeks to unify interested sites and deconstruct barriers to permit high-value HF research.

Warfarin and aspirin in patients with heart failure and sinus rhythm.

BACKGROUND: It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm. METHODS: We designed this trial to determine whether warfarin (with a target international normalized ratio of 2.0 to 3.5) or aspirin (at a dose of 325 mg per day) is a better treatment for patients in sinus rhythm who have a reduced left ventricular ejection fraction (LVEF). We followed 2305 patients for up to 6 years (mean [±SD], 3.5±1.8). The primary outcome was the time to the first event in a composite end point of ischemic stroke, intracerebral hemorrhage, or death from any cause. RESULTS: The rates of the primary outcome were 7.47 events per 100 patient-years in the warfarin group and 7.93 in the aspirin group (hazard ratio with warfarin, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P=0.40). Thus, there was no significant overall difference between the two treatments. In a time-varying analysis, the hazard ratio changed over time, slightly favoring warfarin over aspirin by the fourth year of follow-up, but this finding was only marginally significant (P=0.046). Warfarin, as compared with aspirin, was associated with a significant reduction in the rate of ischemic stroke throughout the follow-up period (0.72 events per 100 patient-years vs. 1.36 per 100 patient-years; hazard ratio, 0.52; 95% CI, 0.33 to 0.82; P=0.005). The rate of major hemorrhage was 1.78 events per 100 patient-years in the warfarin group as compared with 0.87 in the aspirin group (P<0.001). The rates of intracerebral and intracranial hemorrhage did not differ significantly between the two treatment groups (0.27 events per 100 patient-years with warfarin and 0.22 with aspirin, P=0.82). CONCLUSIONS: Among patients with reduced LVEF who were in sinus rhythm, there was no significant overall difference in the primary outcome between treatment with warfarin and treatment with aspirin. A reduced risk of ischemic stroke with warfarin was offset by an increased risk of major hemorrhage. The choice between warfarin and aspirin should be individualized. (Funded by the National Institute of Neurological Disorders and Stroke; WARCEF ClinicalTrials.gov number, NCT00041938.).

Health literacy and the patient with heart failure--implications for patient care and research: a consensus statement of the Heart Failure Society of America.

BACKGROUND: Low health literacy compromises patient safety, quality health care, and desired health outcomes. Specifically, low health literacy is associated with decreased knowledge of one's medical condition, poor medication recall, nonadherence to treatment plans, poor self-care behaviors, compromised physical and mental health, greater risk of hospitalization, and increased mortality. METHODS: The health literacy literature was reviewed for: definitions, scope, risk factors, assessment, impact on health outcomes (cardiovascular disease and heart failure), and interventions. Implications for future research and for clinical practice to address health literacy in heart failure patients were summarized. RESULTS: General health literacy principles should be applied to patients with heart failure, similar to others with chronic conditions. Clinicians treating patients with heart failure should address health literacy using five steps: recognize the consequences of low health literacy, screen patients at risk, document literacy levels and learning preferences, and integrate effective strategies to enhance patients' understanding into practice. CONCLUSION: Although the literature specifically addressing low health literacy in patients with heart failure is limited, it is consistent with the larger body of health literacy evidence. Timely recognition of low health literacy combined with tailored interventions should be integrated into clinical practice.

Resource use and costs of treatment with anticoagulation and antiplatelet agents: results of the WATCH trial economic evaluation.

BACKGROUND: The Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial revealed no significant differences among 1587 symptomatic heart failure patients randomized to warfarin, clopidogrel, or aspirin in time to all-cause death, nonfatal myocardial infarction, or nonfatal stroke. We compared within-trial medical resource use and costs between treatments. METHODS AND RESULTS: We assigned country-specific costs to medical resources incurred during follow-up. Annualized rates of hospitalizations, inpatient and outpatient procedures, and emergency department visits did not differ significantly between groups. Annualized total costs averaged $5901 (95% confidence interval [CI], $4776-$7520) for the aspirin group, $5646 (95% CI, $4903-$6584) for the clopidogrel group, and $5830 (95% CI, $4838-$7400) for the warfarin group. CONCLUSIONS: Consistent with clinical findings, our analyses did not identify significant cost differences between treatments.

Randomized trial of warfarin, aspirin, and clopidogrel in patients with chronic heart failure: the Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial.

BACKGROUND: Chronic heart failure remains a major cause of mortality and morbidity. The role of antithrombotic therapy in patients with chronic heart failure has long been debated. The objective of this study was to determine the optimal antithrombotic agent for heart failure patients with reduced ejection fractions who are in sinus rhythm. METHODS AND RESULTS: This prospective, randomized clinical trial of open-label warfarin (target international normalized ratio of 2.5 to 3.0) and double-blind treatment with either aspirin (162 mg once daily) or clopidogrel (75 mg once daily) had a 30-month enrollment period and a minimum of 12 months of treatment. We enrolled 1587 men and women >/=18 years of age with symptomatic heart failure for at least 3 months who were in sinus rhythm and had left ventricular ejection fraction of

The Warfarin and Antiplatelet Therapy in Heart Failure trial (WATCH): rationale, design, and baseline patient characteristics.

BACKGROUND: The role of anticoagulation in patients with chronic heart failure has long been an area of interest and controversy. Traditionally the goal of anticoagulation has been to prevent embolic events, but recent trials also demonstrated that oral anticoagulation also prevents vascular events in patients with prior myocardial infarction, who constitute the majority of heart failure patients. Although antiplatelet agents also reduce postinfarction vascular events, few data are available in heart failure patients, and some evidence suggests that aspirin may also have the potential to worsen heart failure morbidity and mortality, possibly by interfering with the effects of angiotensin-converting enzyme inhibitors. Methods and results The Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial was undertaken to determine the optimal antithrombotic agent for heart failure patients. WATCH was a prospective-randomized trial in which symptomatic heart failure patients in sinus rhythm with ejection fractions < or =35% taking angiotensin-converting enzyme inhibitors (unless not tolerated) and diuretics were randomized to open-label warfarin (target International Normalized Ratio 2.5-3.0) or double-blind antiplatelet therapy with aspirin 162 mg or clopidogrel 75 mg. Two primary comparisons were specified: anticoagulation with warfarin versus antiplatelet therapy with aspirin and antiplatelet therapy with clopidogrel versus antiplatelet therapy with aspirin. The primary outcome is the composite of death from all causes, nonfatal myocardial infarction, and nonfatal stroke analyzed as time to first event using the intent-to-treat approach. The secondary endpoint was the broader composite of death from all causes, nonfatal myocardial infarction, non-fatal stroke, and hospitalizations for worsening heart failure, unstable angina pectoris, and systemic or pulmonary artery embolic events. Additional prespecified analyses include heart failure events, coronary events, and resource utilization. CONCLUSIONS: Although the trial was designed to enter 4500 patients, it was terminated 18 months prematurely in June 2003 by the VA Cooperative Study Program because of poor enrollment with a resulting reduction of its power to achieve its original objective. This manuscript describes the study rationale, protocol design, and the baseline characteristics of the 1587 patients who were entered into the study. The WATCH trial will help define the optimal approach to antithrombotic therapy in the contemporary management of patients with chronic heart failure resulting from left ventricular systolic dysfunction.