Low-risk Atrial Fibrillation Patients Research Articles

Soluble CD40 Ligand, Platelet Surface CD40 Ligand, and Total Platelet CD40 Ligand in Atrial Fibrillation: Relationship to Soluble P-Selectin, Stroke Risk Factors, and Risk Factor Intervention

Abnormal levels of soluble CD40 ligand (sCD40L) have been reported in patients with hypertension, coronary artery disease, diabetes mellitus, heart failure, and stroke, all of which are conditions that are associated with nonvalvular atrial fibrillation (AF). We hypothesized the following: (1) CD40 ligand (CD40L)-related indexes (ie, platelet surface expressed CD40L, the soluble fragment of CD40L [sCD40L], and the total amount of CD40L per platelet [pCD40L]) are elevated in patients with AF compared to control subjects; (2) these indexes correlate with soluble P-selectin (sP-selectin), which is an established platelet marker; and (3) these indexes differentiate "high-risk" from "low-risk" subjects.We performed a case-control study of 121 AF patients, 71 "disease control subjects," and 56 "healthy control subjects." Peripheral venous levels of platelet surface-expressed CD40L were analyzed by flow cytometry, while levels of sCD40L, pCD40L, and sP-selectin were measured by enzyme-linked immunosorbent assay.AF patients had significantly higher sCD40L levels compared to healthy control subjects (p = 0.042), with no difference in platelet surface CD40L and pCD40L levels. A positive correlation was noted between levels of sCD40L and pCD40L, and not with sP-selectin. CD40L-related indexes failed to distinguish between high-risk and low-risk AF patients. AF patients receiving optimal antithrombotic therapy had significantly lower pCD40L levels (p < 0.001) compared to control subjects. Optimized AF management also resulted in significant reductions in the levels of sCD40L (p = 0.023) and pCD40L (p < 0.001).CD40L-related indexes are not useful in the risk stratification of AF patients, and abnormal sCD40L levels can be reduced by intense multifactorial risk management. While there is a significant, albeit modest, excess of platelet activation in AF patients (as measured by sCD40L levels) compared to healthy control subjects, this is not in excess of that seen in patients with underlying cardiovascular diseases.

Aspirin Reasonable for Low-Risk Atrial Fibrillation Patients.

Aspirin is inferior to warfarin for prevention of thromboembolic events in most patients with atrial fibrillation, but are there subgroups for which aspirin is good enough? This study evaluated rates of stroke in 892 patients with atrial fibrillation who …

The stroke prevention in atrial fibrillation III study: Rationale, design, and patient features

Clinical trials have consistently shown warfarin's high degree of efficacy for stroke prevention in patients with nonvalvular atrial fibrillation (AF). However, aspirin therapy may be sufficient for large subgroups of low-risk AF patients. In addition, many elderly AF patients cannot receive or sustain adjusted-dose warfarin because of bleeding (minor and major), drug interactions, and other disutility. For such patients, a safer and easier to administer anticoagulation regimen is desirable. The Stroke Prevention in Atrial Fibrillation (SPAF) III Study has two components, based on stratification of patients as high-risk or low-risk for thromboembolism. In high-risk patients, adjusted-dose warfarin (INR 2.0 to 3.0) is compared with low-intensity, fixed-dose warfarin (INR 1.2 to 1.5 initial dose adjustment) plus aspirin (325 mg/d) in a randomized trial. Patients categorized as low-risk all receive aspirin 325 mg/d and are followed-up to assess the reliability and durability of the risk stratification scheme. Medications are administered open-label. Primary events (ischemic strokes and systemic emboli) are assessed by a local neurologist and verified by an Events Committee, neither having knowledge of assigned treatment. Transesophageal echocardiography is obtained at entry, when possible. High-risk criteria for the 1,044 patients in the randomized trial (mean age,=72 years) are impaired left ventricular function (45%), systolic blood pressure >160 mm Hg (32%), prior thromboembolism (38%), and female gender over age 75 years (24%). The mean INR is 2.4 for adjusted-dose and 1.3 for fixed-dose warfarin, with mean daily doses of 3.9 mg and 2.1 mg, respectively. Compared with high-risk patients, those categorized as low-risk (n=892) are younger (mean age, 67 years; P<.001), with lower mean systolic blood pressures, (P<.001), and less ischemic heart disease (P<.001), but similar diastolic blood pressures. Given the large variation in stroke rate among AF patients, blanket recommendations for antithrombotic prophylaxis of all AF patients are not optimal. Patient age, gender, left ventricular function, and systolic blood pressure may be useful markers of the inherent thromboembolic risk and may influence selection of antithrombotic therapy to prevent stroke in AF patients.