Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation: analysis of 2012 participants in the SPAF I-III clinical trials. The Stroke Prevention in Atrial Fibrillation (SPAF) Investigators. (9/1963)

BACKGROUND AND PURPOSE: Nonvalvular atrial fibrillation (AF) is a strong, independent risk factor for stroke, but the absolute rate of stroke varies widely among AF patients, importantly influencing the potential benefit of antithrombotic prophylaxis. We explore factors associated with ischemic stroke in AF patients taking aspirin. METHODS: We performed multivariate logistic regression analysis of 2012 participants given aspirin alone or in combination with low, inefficacious doses of warfarin in the Stroke Prevention in Atrial Fibrillation I-III trials followed for a mean of 2.0 years, during which 130 ischemic strokes were observed. RESULTS: Age (relative risk [RR]=1.8 per decade, P<0.001), female sex (RR=1.6, P=0.01), history of hypertension (RR=2.0, P<0.001), systolic blood pressure >160 mm Hg (RR=2.3, P<0.001), and prior stroke or transient ischemic attack (RR=2.9, P<0.001) were independently associated with increased stroke risk. Regular consumption of >/=14 alcohol-containing drinks per week was associated with reduced stroke risk (adjusted RR=0.4, P=0.04). Among SPAF III participants, estrogen hormone replacement therapy was associated with a higher risk of ischemic stroke (adjusted RR=3.2, P=0.007). With the use of these variables, a risk stratification scheme for primary prevention separated participants into those with high (7.1%/y, 22% of the cohort), moderate (2.6%/y, 37% of the cohort), and low (0.9%/y, 41% of the cohort) rates of stroke. Ischemic strokes in low-risk participants were less often disabling (P<0.001). CONCLUSIONS: Patients with AF who have high and low rates of stroke during treatment with aspirin can be identified. However, validation of our risk stratification scheme is necessary before it can be applied with confidence to clinical management. Postmenopausal estrogen replacement therapy and moderate alcohol consumption may additionally modify the risk of stroke in AF, but these findings require confirmation.  (+info)

Prediction of the international normalized ratio and maintenance dose during the initiation of warfarin therapy. (10/1963)

AIMS: A pharmacokinetic/pharmacodynamic model, with Bayesian parameter estimation, was used to retrospectively predict the daily International Normalized Ratios (INRs) and the maintenance doses during the initiation of warfarin therapy in 74 inpatients. METHODS: INRs and maintenance doses predicted by the model were compared with the actual INRs and the eventual maintenance dose. Cases with drugs or medical conditions interacting with warfarin or receiving concurrent heparin therapy were not excluded. As the study was retrospective, model predictions of the maintenance dose were not those that were administered. Mean prediction error (MPE) and percentage absolute prediction errors (PAPE) were used to assess the model predictions. RESULTS: INR MPE ranged from -0.07 to 0.06 and median PAPE from 10% to 20%. Dose MPE ranged from -0.7 to 0.17 mg and median PAPE from 16.7% to 37.5%. Accurate and precise dose predictions were obtained after 3 or more INR feedback's. CONCLUSIONS: This study shows that the model can accurately predict daily INRs and the maintenance dose in this sample of cases. The model can be incorporated into computer decision-support systems for warfarin therapy and may lead to improvement in the initiation of warfarin therapy.  (+info)

Hyperimmunoglobulin E syndrome associated with nephrotic syndrome. (11/1963)

A 21-year-old man was admitted to Kure National Hospital with nephrotic syndrome in September 1996. He had suffered from an intractable pruritic skin rash and recurrent subcutaneous abscesses caused by the hyperimmunoglobulin E syndrome since the age of 18 months. Renal biopsy gave a diagnosis of membranoproliferative glomerulonephritis. Steroid therapy decreased urinary protein loss and hypoproteinemia, and his pruritic skin rash was improved. Patients with hyperimmunoglobulin E syndrome have a defective immune response, especially to Staphylococcus aureus infection. Continuous antigen stimulation may have caused this patient's renal histological damage as in immune complex glomerulonephritis.  (+info)

Effects of lovastatin and warfarin on early carotid atherosclerosis: sex-specific analyses. Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group. (12/1963)

BACKGROUND: Few clinical trials have documented the efficacy of preventive treatment in asymptomatic women. METHODS AND RESULTS: Lovastatin and minidose warfarin were evaluated in a factorially designed, placebo-controlled, randomized trial. The primary outcome was 3-year change in the mean maximum intimal-medial thickness of the carotid arteries as measured by B-mode ultrasonography. Participants (n=919) were randomized to 1 of 4 treatment groups: lovastatin alone, warfarin alone, lovastatin+warfarin combination, or a double-placebo group. Eligible participants were asymptomatic for cardiovascular disease, with evidence of early carotid atherosclerosis and moderately elevated LDL cholesterol level. Almost half (n=445) of the participants were women. To avoid confounding, 117 women taking estrogen were excluded from analysis. Both sexes experienced reductions in disease progression with lovastatin; there was no evidence of an overall sex x treatment interaction (P=0.72). When estimates of the sex-specific results were examined post hoc, women experienced disease regression to the greatest extent with the lovastatin + warfarin combination (P=0.02), although the women on lovastatin alone also had a reduction in progression (P=0.09). Men experienced the greatest reduction with lovastatin alone (P=0.02), although there is a suggestion that warfarin may also reduce progression to some extent. CONCLUSIONS: Lovastatin is beneficial in reducing disease progression in women and men. Warfarin has no effect in women, although it may reduce progression in men. In men, warfarin does not add to the benefit of lovastatin and has no advantage over lovastatin alone.  (+info)

Lower extremity hematoma as a complication of warfarinization in patients with artificial heart valves. (13/1963)

Four cases of lower extremity hematoma in patients undergoing anticoagulant therapy after heart valve replacement are herein reported, with special emphasis on the comparative diagnostic value of ultrasonography and computerized tomography. Although conservative management is sufficient for patients with no neurological impairment, needle aspiration after autolysis of the hematoma, which can be confirmed by CT study, is also recommended.  (+info)

Treatment of pulmonary thromboembolism. (14/1963)

The epidemiology, diagnosis, treatment, and prophylaxis of PE are rapidly advancing. Our array of diagnostic imaging tools has expanded to include echocardiography and spiral chest CT with contrast. We have also gained a keen appreciation for the importance of risk stratification of our patients. The decision to administer thrombolysis or undertake embolectomy may now depend upon the presence of right ventricular dysfunction even if systemic arterial pressure is normal. Finally, the availability of low molecular weight heparins broadens our options for pharmacologic management.  (+info)

Enantioselective binding sites on bovine serum albumin to dansyl amino acids. (15/1963)

The enantioselective binding sites on bovine serum albumin were examined by HPLC using 19 racemic 5-N, N-dimethylamino-1-naphthalenesulfonyl derivatives of alpha-amino acids (dansyl amino acids) as chiral probes. On a bovine serum albumin bonded chiral stationary phase, seven L-forms eluted faster than their D-forms, while ten D-forms eluted before their L-forms. It was speculated that either two classes or two different binding sites exist on bovine serum albumin which can be distinguished by N-dansyl-L-proline and N-dansyl-D-norvaline. This was confirmed by fluorometric experiments where non-fluorescent 1-naphthalenesulfonyl derivatives were synthesized and competitive adsorption experiments were performed.  (+info)

Additional risk factors in atrial fibrillation patients not receiving warfarin. (16/1963)

OBJECTIVE: To study how many elderly inpatients with previously diagnosed atrial fibrillation were not receiving anticoagulant prophylaxis, and the prevalence of additional risk factors in these patients. METHODS: All new admissions to a department of medicine for the elderly were screened for atrial fibrillation. Additional risk factors were analysed in those with established atrial fibrillation who were not receiving warfarin. Previous hospital admissions, documentation of why prophylaxis was not being used and use of aspirin as an alternative agent were also examined. RESULTS: 56 patients had previously diagnosed atrial fibrillation; 82% were not taking warfarin and 71% of these were not on aspirin either. All patients not taking warfarin had one additional risk factor for stroke and 95% had two or more. Fifty-two percent had attended hospital when atrial fibrillation was present within the previous 3 years and there was nothing documented in their records to explain why anticoagulation had not been used. CONCLUSIONS: Most elderly inpatients with established atrial fibrillation were not taking warfarin. All had additional risk factors for stroke, which increase the absolute benefit of anticoagulation.  (+info)