Ralph L. Sacco

Warfarin and Aspirin in Patients with Heart Failure and Sinus Rhythm

BACKGROUNDnIt is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm.nnnMETHODSnWe 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.nnnRESULTSnThe 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).nnnCONCLUSIONSnAmong 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.).

Endothelial function in individuals with coronary artery disease with and without type 2 diabetes mellitus

The goal of this study was to determine if individuals with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) had greater endothelial dysfunction (ED) than individuals with only CAD. Flow-mediated dilation (FMD), calculated as percentage increase in brachial artery diameter in response to postischemic blood flow, was measured after an overnight fast in 2 cohorts. The first cohort included 76 participants in the Northern Manhattan Study with CAD; 25 also had T2DM. The second cohort was composed of 27 individuals with both T2DM and CAD who were participants in a study of postprandial lipemia. Combined, we analyzed 103 patients with CAD: 52 with T2DM (T2DM+) and 51 without T2DM (T2DM-). The 52 CAD T2DM+ subjects had a mean FMD of 3.9% +/- 3.2%, whereas the 51 CAD T2DM- subjects had a greater mean FMD of 5.5% +/- 4.0% (P < .03). An investigation of various confounders known to affect FMD identified age and body mass index as the only significant covariates in a multiple regression model. Adjusting for age and body mass index, we found that FMD remained lower in T2DM+ subjects compared with T2DM- subjects (difference, -1.99%; P < .03). In patients with CAD, the concomitant presence of T2DM is independently associated with greater ED, as measured by FMD. This finding may be relevant to the greater early and late morbidity and mortality observed in patients with both CAD and T2DM.

CHA2DS2-VASC SCORE AND ADVERSE EVENTS IN PATIENTS WITH HEART FAILURE AND SINUS RHYTHM

The CHA2DS2-Vasc score was developed to predict stroke and other adverse clinical events in patients with atrial fibrillation. There is also interest in assessing its performance in patients with systolic heart failure (HF) in sinus rhythm, such as those enrolled in the WARCEF trial.nnCHA2DS2-Vasc