These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.

Background Due to its association with death and disability, stroke is a focus of outcomes in atrial fibrillation (AF) research. International Classification of Disease 9th (ICD-9) edition codes are commonly used to identify stroke in research, particularly in large administrative data. We sought to assess the validity of ICD-9 codes in stroke case ascertainment and for AF across three institutions. Methods and Results Participating centers included Boston Medical Center (safety net hospital), Geisinger Health System (rural Pennsylvania), and the University of Alabama (academic center in the southeastern “stroke belt”). ICD-9 codes for ischemic stroke (433-434, 436) and intracranial hemorrhage (ICH) (430-432) identified 1,812 stroke cases with an associated code for atrial fibrillation (427.31) from 2006-2010. Cases were vetted through chart review with final adjudication by a stroke neurologist. Review deemed 94.2% of ICD-9 identified stroke cases valid with decreased accuracy for concurrent AF diagnosis (82.28%) and stroke attributable to AF (72.8%). Among events with “without infarction” modifiers, 7.2% were valid strokes. ICD-9 stroke code accuracy did not differ by stroke type or site. Stroke code 434 displayed higher accuracy than 433 (94.4% vs. 85.2%; p<0.01) and primary stroke codes were more accurate than non-primary codes (97.2% vs. 83.7%; p<0.0001). Conclusions Using ICD-9 stroke and AF codes to identify patients with stroke plus AF resulted in inaccuracies. Given the expanded financial and policy implications of patient-oriented research, conclusions derived solely from administrative data without validation of outcome events should be interpreted with caution.

Warfarin is the most commonly used oral anticoagulant in sub‐Saharan Africa. Dosing is challenging due to a narrow therapeutic index and high interindividual variability in dose requirements. To evaluate the genetic factors affecting warfarin dosing in black‐Africans, we performed a meta‐analysis of 48 studies (2,336 patients). Significant predictors for CYP2C9 and stable dose included rs1799853 (CYP2C9*2), rs1057910 (CYP2C9*3), rs28371686 (CYP2C9*5), rs9332131 (CYP2C9*6), and rs28371685 (CYP2C9*11) reducing dose by 6.8, 12.5, 13.4, 8.1, and 5.3 mg/week, respectively. VKORC1 variants rs9923231 (‐1639G>A), rs9934438 (1173C>T), rs2359612 (2255C>T), rs8050894 (1542G>C), and rs2884737 (497T>G) decreased dose by 18.1, 21.6, 17.3, 11.7, and 19.6 mg/week, respectively, whereas rs7294 (3730G>A) increased dose by 6.9 mg/week. Finally, rs12777823 (CYP2C gene cluster) was associated with a dose reduction of 12.7 mg/week. Few studies were conducted in Africa, and patient numbers were small, highlighting the need for further work in black‐Africans to evaluate genetic factors determining warfarin response.