PURPOSE: The genes for cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) have been identified as important genetic determinants of warfarin dosing and have been studied. We developed warfarin algorithm for Korean patients with stroke and compared the accuracy of warfarin dose prediction algorithms based on the pharmacogenetics. MATERIALS AND METHODS: A total of 101 patients on stable maintenance dose of warfarin were enrolled. Warfarin dosing algorithm was developed using multiple linear regression analysis. The performance of all the algorithms was characterized with coefficient of determination, determined by linear regression, and the mean of percent deviation was used to predict doses from the actual dose. In addition, we compared the performance of the algorithms using percentage of predicted dose falling within ±20% of clinically observed doses and dividing the patients into a low-dose group (≤3 mg/day), an intermediate-dose group (3-7 mg/day), and high-dose group (≥7 mg/day). RESULTS: A new developed algorithms including the variables of age, body weight, and CYP2C9 and VKORC1 genotype. Our algorithm accounted for 51% of variation in the warfarin stable dose, and performed best in predicting dose within 20% of actual dose and intermediate-dose group. CONCLUSION: Our warfarin dosing algorithm may be useful for Korean patients with stroke. Further studies to elucidate clinical utility of genotype-guided dosing and find the additional genetic association are necessary.
Aged ; *Algorithms ; Anticoagulants/*administration & dosage/therapeutic use ; Cytochrome P-450 CYP2C9/*genetics ; Dose-Response Relationship, Drug ; Female ; Genotype ; Humans ; International Normalized Ratio ; Linear Models ; Male ; Middle Aged ; Multivariate Analysis ; Pharmacogenetics ; Regression Analysis ; Republic of Korea ; Stroke/*drug therapy/ethnology ; Vitamin K Epoxide Reductases/*genetics ; Warfarin/*administration & dosage/therapeutic use

BACKGROUND/AIMS: Hyponatremia is a well-known risk factor for poor outcomes in Western studies of heart failure (HF) patients. We evaluated the predictive value of hyponatremia in hospitalized Asian HF patients. METHODS: The Clinical Characteristics and Outcomes in the Relation with Serum Sodium Level in Asian Patients Hospitalized for Heart Failure (the COAST) study enrolled hospitalized patients with systolic HF (ejection fraction < 45%) at eight centers in South Korea, Taiwan, and China. The relationship between admission sodium level and clinical outcomes was analyzed in 1,470 patients. RESULTS: The mean admission sodium level was 138 +/- 4.7 mmol/L, and 247 patients (16.8%) had hyponatremia defined as Na+ < 135 mmol/L. The 12-month mortality was higher in hyponatremic patients (27.9% vs. 14.6%, p < 0.001), and hyponatremia was an independent predictor of 12-month mortality (hazard ratio, 1.72; 95% confidence interval, 1.12 to 2.65). During hospital admission, 57% of hyponatremic patients showed improvement without improvement in their clinical outcomes (p = 0.620). The proportion of patients with optimal medical treatment was only 26.5% and 44.2% at admission and discharge, respectively, defined as the combined use of angiotensin-converting-enzyme inhibitor/angiotensin receptor blocker and beta-blocker. Underuse of optimal medical treatment was more pronounced in hyponatremic patients. CONCLUSIONS: In hospitalized Asian HF patients, hyponatremia at admission is common and is an independent predictor of poor clinical outcome. Furthermore, hyponatremic patients receive less optimal medical treatment than their counterparts.
Aged ; Aged, 80 and over ; Asia/epidemiology ; *Asian Continental Ancestry Group ; Biomarkers/blood ; Cardiovascular Agents/therapeutic use ; Disease-Free Survival ; Female ; Guideline Adherence ; Healthcare Disparities ; Heart Failure/*diagnosis/drug therapy/ethnology/mortality/physiopathology ; *Hospitalization ; Humans ; Hyponatremia/blood/*diagnosis/drug therapy/ethnology/mortality ; Male ; Middle Aged ; Practice Guidelines as Topic ; Predictive Value of Tests ; Proportional Hazards Models ; Risk Factors ; Sodium/*blood ; Stroke Volume ; Time Factors ; Treatment Outcome