Efficacy and Safety of Dabigatran Etexilate vs. Warfarin in Asian RE-LY Patients According to Baseline Renal Function or CHADS2 Score.

BACKGROUND: In Asian patients in RE-LY, dabigatran etexilate (DE) was as effective as warfarin, with a significantly lower bleeding risk. We evaluated the relationship between baseline renal function or CHADS2 score and efficacy or safety outcomes in these patients. METHODS AND RESULTS: Asian patients (n=2,782) were categorized according to baseline renal function or CHADS2 score, and efficacy and safety outcomes were analyzed for DE (110 mg and 150 mg b.i.d.) vs. warfarin. There was an increase in the rates of stroke/systemic embolism and major bleeding with worsening renal function and CHADS2 score. For stroke/systemic embolism (primary efficacy endpoint), there was no treatment interaction for dabigatran at either 110 or 150 mg b.i.d. compared with warfarin related to patients' baseline renal function (Pinteraction=0.56 for DE 110 mg and 0.62 for DE 150 mg vs. warfarin) or CHADS2 score (Pinteraction=0.68 for DE 110 mg and 0.31 for DE 150 mg vs. warfarin). For major bleeding, there was no treatment interaction by creatinine clearance category observed for either dose (Pinteraction=0.60 and 0.62 for DE 110 mg and DE 150 mg, respectively). Baseline CHADS2 score had no significant effect on bleeding event rates with DE vs. warfarin. CONCLUSIONS: Bleeding and stroke rates in Asian patients varied according to renal function and CHADS2 score, but the relative benefits of DE over warfarin were preserved when analyzed by subcategories.

Utility of urinalysis in discriminating cardioembolic stroke mechanism.

OBJECTIVE: To determine whether elevated urine erythrocyte (red blood cell) and leukocyte (white blood cell) counts, reflecting concomitant renal and cerebral emboli of cardiac origin, would be useful in discriminating cardioembolic (CE) from non-CE stroke in acute ischemic stroke. DESIGN: Consecutive patients presenting within 24 hours of ischemic stroke over 3(3/4) years were studied. Patient medical history and urinalysis data, including white blood cell count, red blood cell count, specific gravity, and glucose and protein levels at admission, were analyzed and compared with the final determination of stroke subtype. Multivariate analysis (CE vs non-CE stroke) was performed using a classification and regression tree that included all 5 urine variables as potential predictors. Additional predictors entered into the classification and regression tree model were age, presence of urinary tract infection at admission, history of hypertension, history of diabetes mellitus, and serum creatinine level. RESULTS: A total of 341 individuals met the study criteria. Their mean age was 68.6 years; 49.8% were female, 70.9% were white, and 38.7% had the CE stroke subtype. In bivariate analysis, age (P = .009), urine white blood cell count (P = .02), urine red blood cell count (P = .005), urine specific gravity (P = .02), and serum creatinine level (P = .02) were significantly higher in those with the CE vs the non-CE stroke subtype. In the classification and regression tree, 58.3% of those with CE stroke were correctly classified and 84.7% of those with non-CE stroke were correctly classified, for an overall accuracy of 71.5%. The best single predictor for the CE stroke subtype was a white blood cell count of greater than 14.5/microL, followed by a red blood cell count of greater than 41.7/microL and a serum creatinine level greater than 1.08 mg/dL (>95.5 micromol/L). Based on the distribution in the first 2 divisions in the tree, a patient could be placed into 1 of 4 categories that corresponded to 3 levels of CE stroke likelihood: low (25%), moderate (50%), and high (80%). CONCLUSION: Urinalysis may have utility in the early identification of the CE stroke subtype in patients with acute ischemic stroke.

Nephritic urinary sediment in embolic renal infarction.

Emboli to the renal arteries occurs most often in patients with underlying cardiac disease. Hematuria is a common feature of renal infarction, but the finding of erythrocyte casts in cases of renal infarction has not been commonly reported. We report a case of renal artery embolization in a patient who had transient nephritic urine sediment, and review the significance of this finding.

Eosinophiluria in atheroembolic renal disease.

PURPOSE AND PATIENTS: Eosinophiluria has been reported in acute interstitial nephritis and other renal diseases, but its presence in atheroembolic renal disease (AERD) has not been previously established. AERD has been identified as a cause of acute and chronic renal failure, particularly in elderly patients with advanced atherosclerosis and in those patients who have undergone manipulation or intervention of the abdominal aorta, renal artery, or coronary artery. The definitive diagnosis is made by renal biopsy. However, many patients are too acutely ill to tolerate renal biopsy and, in recent years, peripheral eosinophilia, hypocomplementemia, and thrombocytopenia have been recognized in association with AERD. Previous studies have reported that AERD is associated with an inactive renal sediment and an absence of urine eosinophils. We reviewed our experience over a 4-year period with 24 patients with renal biopsy-proven AERD. RESULTS: Urine eosinophils were evaluated in nine patients to help determine the cause of their renal deterioration. Seven of these patients presented with evidence of vascular disease. Three patients had procedures involving manipulation of the abdominal aorta. Physical examination revealed findings of atheroembolism in three of nine patients. Overall, eight of nine patients had a positive Hansel's stain for eosinophiluria. Six of eight patients had more than 5% of their urinary white cell count as eosinophils. The reason for failure of previous studies to detect eosinophiluria in AERD is unclear but may have been related to the use of Wright's stain instead of Hansel's stain. CONCLUSION: In the evaluation of acute renal insufficiency, eosinophiluria may indicate AERD in addition to the other known causes for this finding.

Cholesterol embolization: clinical findings and implications.

The clinical characteristics of 13 patients with cholesterol embolization are described. Embolization occurred spontaneously in 2 patients and after a vascular procedure in 11. Acute but vague symptoms were reported by 11 of the 13 patients; skin findings of purple toes or livedo reticularis and renal dysfunction were present in 12 patients, 5 of whom required dialysis. Blood pressure elevation occurred in all 13 patients, eosinophilia in 9 of 10 and elevated sediment rate in 5 of 6. Death occurred within 6 months in three patients. Two distinct patterns were observed: mild (five patients) and severe (eight patients). Compared with the severe pattern, patients with mild cholesterol embolization had early symptoms less frequently (two of five versus eight of eight), less severe renal insufficiency (serum creatinine 1.7 versus 7.4 mg/100 ml), less of an increase in blood pressure (22 versus 34 mm Hg) and later development of skin lesions (14 versus 6 weeks). Baseline blood pressure and development of eosinophilia were comparable in both groups. The presentation of cholesterol embolization is often subtle and may go unrecognized, particularly in its mild form. As vascular interventions increase in elderly atherosclerotic and hypertensive patients, so too will the incidence of this disorder.