Validating the Prognostic Utility of the ABCD-GENE Score in Asian Patients with Acute Coronary Syndrome Patients on Clopidogrel.

Background: The ABCD-GENE score, which links cytochrome P450 2C19 (CYP2C19) phenotype and high platelet reactivity (HPR) to the risk of major adverse cardiovascular events (MACE) in clopidogrel users, has been validated in white and Japanese populations. The prognostic implications of the score in other Asian cohorts, however, have been largely unchartered. The aim of this study was to validate the prognostic utility of the ABCD-GENE score in a heterogeneous Asian acute coronary syndrome (ACS) cohort. Methods and Results: In this single-centre, retrospective cohort evaluation of 423 ACS patients, the objectives were to characterise the best cut-off score for MACE prognostication by comparing the adjusted 1-year risk of MACE between groups above and below the candidate cut-off scores using Cox regression; and for on-clopidogrel HPR prediction using receiver operating characteristic (ROC) analysis and Youden's index. In the adjusted Cox model, an ABCD-GENE score cut-off at 10 points significantly predicts the 1-year risk of MACE (adjusted HR 3.771; 95% CI [1.041-13.661]). Female sex, baseline LDL, history of ACS and angiotensin receptor blocker use were additional independent predictors of MACE. On ROC analysis the ideal cut-off for HPR prediction was 7 points. However, that did not independently predict the 1-year risk of MACE (adjusted HR 1.595; 95% CI [0.425-5.989]). Conclusion: The original ABCD-GENE score 10-point cut-off moderately predicts MACE in a heterogeneous, Asian ACS population at 1 year. Additional predictors of MACE were also identified in the present cohort, and these findings should be prospectively validated in larger ACS cohorts.

Incidence of thromboembolic and bleeding events in patients with newly diagnosed nonvalvular atrial fibrillation: An Asian multicenter retrospective cohort study in Singapore.

BACKGROUND: Real-world effectiveness and safety of antithrombotics in nonvalvular atrial fibrillation (NVAF) patients in Singapore has not been thoroughly studied. HYPOTHESIS: Users of various antithrombotics experience a significantly different risk of stroke and major bleed compared with warfarin users. METHODS: This multicenter retrospective cohort study included patients age ≥ 21 years newly diagnosed with NVAF between July 2012 and September 2015. Using electronic medical records, data on patients' demographics, antithrombotics prescribed, and CHA2 DS2 -VASc and HAS-BLED risk factors were collected. Patients were followed for 1 year from diagnosis for the primary effectiveness and safety endpoints of incident stroke or systemic embolism and major bleed, respectively. The secondary safety endpoint was overall bleed. Hazard ratios (HR) were determined from Cox regression. RESULTS: Of 743 patients included, 224 were on warfarin, 156 on direct oral anticoagulants (DOACs), 277 on single antiplatelet therapy (SAPT), 28 on dual antiplatelet therapy (DAPT), and 58 on no therapy. Mean age (±SD) was 68.7 ± 13.0 years. Compared with warfarin users, SAPT (adjusted [adj.] HR: 3.70, 95% confidence interval [CI]: 1.21-11.3) and DAPT users (adj. HR: 10.1, 95% CI: 1.51-67.2) were more likely to develop thromboembolic outcomes. Also, DOAC users (adj. HR: 0.304, 95% CI: 0.158-0.585), SAPT users (adj. HR: 0.142, 95% CI: 0.0680-0.295), and DAPT users (adj. HR: 0.112, 95% CI: 0.0146-0.857) were less likely to experience any bleed compared with warfarin users. CONCLUSIONS: SAPT and DAPT are less effective than warfarin in NVAF patients. DOACs may be considered in view of lower risk of overall bleed.

Automated systems to identify relevant documents in product risk management.

BACKGROUND: Product risk management involves critical assessment of the risks and benefits of health products circulating in the market. One of the important sources of safety information is the primary literature, especially for newer products which regulatory authorities have relatively little experience with. Although the primary literature provides vast and diverse information, only a small proportion of which is useful for product risk assessment work. Hence, the aim of this study is to explore the possibility of using text mining to automate the identification of useful articles, which will reduce the time taken for literature search and hence improving work efficiency. In this study, term-frequency inverse document-frequency values were computed for predictors extracted from the titles and abstracts of articles related to three tumour necrosis factors-alpha blockers. A general automated system was developed using only general predictors and was tested for its generalizability using articles related to four other drug classes. Several specific automated systems were developed using both general and specific predictors and training sets of different sizes in order to determine the minimum number of articles required for developing such systems. RESULTS: The general automated system had an area under the curve value of 0.731 and was able to rank 34.6% and 46.2% of the total number of 'useful' articles among the first 10% and 20% of the articles presented to the evaluators when tested on the generalizability set. However, its use may be limited by the subjective definition of useful articles. For the specific automated system, it was found that only 20 articles were required to develop a specific automated system with a prediction performance (AUC 0.748) that was better than that of general automated system. CONCLUSIONS: Specific automated systems can be developed rapidly and avoid problems caused by subjective definition of useful articles. Thus the efficiency of product risk management can be improved with the use of specific automated systems.