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Late stent thrombosis in a patient with CYP2C19*3/*17 genotype and clopidogrel high on-treatment platelet reactivity

Tan SSN, Koh KT, Tiong LL, Ong TK, Fong AYY

Pharmacogenomics, 2018 10;19(15):1151-1157.
PMID: 30191759 DOI: 10.2217/pgs-2018-0082

AIM: Recurrent thrombotic events still occur despite dual antiplatelet therapy in patient's post percutaneous coronary intervention (PCI) could be attributed to high on-treatment platelet reactivity.
METHODS: A 44-year-old male, who had staged PCI to left anterior descending (LAD) 2 weeks after an anterior MI, with a drug-coated stent was readmitted with new anterior STEMI 35 days later. Coronary angiogram revealed mid-stent thrombus in situ. He had further uncomplicated PCI. Platelet function testing and genotyping showed clopidogrel high on-treatment platelet reactivity and CYP2C19*3/*17 genotype. Ticagrelor was commenced.
RESULTS & CONCLUSION: This case study is the first reported in Malaysia to document a patient with a CYP2C19*3/*17 genotype presenting with a stent thrombosis after an uncomplicated index PCI procedure.
Development and validation of Join Clinical Trial Questionnaire (JoinCT)

Tan SH, King TL, Tan SSN, Lai WH, Bujang MA, Voon PJ

Asia Pac J Clin Oncol, 2023 Nov 09.
PMID: 37943536 DOI: 10.1111/ajco.14034

AIM: Participant recruitment has always been a major challenge in clinical trials. This study aimed to develop and validate the Join Clinical Trial Questionnaire (JoinCT), exploring the willingness to join a clinical trial and associated factors in patients.
METHODS: This questionnaire development study involved four phases: (i) exploring and understanding the subject matter, (ii) questionnaire development, (iii) content validity testing, and lastly, (iv) field-testing of the questionnaire. For the field-testing phase, a cross-sectional self-administered survey of JoinCT was conducted among cancer patients with various socio-demographic backgrounds and medical conditions. Besides content validity, Cronbach's alpha was used to evaluate the internal consistency of domains, and confirmatory factor analysis was used to evaluate the model fit of the JoinCT framework.
RESULTS: A total of 389 respondents participated in the survey. Based on the results obtained from a field data collection phase, JoinCT consisted of four independent variables domains, namely "knowledge", "perception of benefits", "perception of risks", and "confidence". The only dependent variable was the willingness to participate in a clinical trial. The minimum Cronbach's alpha was 0.937, and the model fit for the overall framework of JoinCT is also excellent with Comparative Fit Index (> 0.90), root mean square error approximation (
Fulltext Barriers And Challenges Of Multidisciplinary Teams In Oncology Management: A Scoping Review Protocol

Law NLW, Hong LW, Tan SSN, Foo CJ, Lee D, Voon PJ

BMJ Open, 2024 Feb 10;14(2):e079559.
PMID: 38341218 DOI: 10.1136/bmjopen-2023-079559

INTRODUCTION: Multidisciplinary teams (MDTs) are integral to oncology management, involving specialised healthcare professionals who collaborate to develop individualised treatment plans for patients. However, as cancer care grows more complex, MDTs must continually adapt to better address patient needs. This scoping review will explore barriers and challenges MDTs have encountered in the past decade; and propose strategies for optimising their utilisation to overcome these obstacles and improve patient care.
METHODS AND ANALYSIS: The scoping review will follow Arksey and O'Malley's framework and begin with a literature search using keywords in electronic databases such as PubMed/MEDLINE, Scopus and PsychINFO, covering the period from January 2013 to December 2022 and limited to English language publications. Four independent reviewers will screen titles and abstracts based on predefined inclusion criteria, followed by full-text review of selected titles. Relevant references cited in the publications will also be examined. A Preferred Reporting Items for Systematic reviews and Meta-Analyses flow diagram will be utilised to illustrate the methodology. Data from selected publications will be extracted, analysed, and categorised for further analysis.
ETHICS AND DISSEMINATION: The results of the scoping review will provide a comprehensive overview of the barriers and challenges encountered by oncology MDTs over the past decade. These findings will contribute to the existing literature and provide insights into areas that require improvement in the functioning of MDTs in oncology management. The results will be disseminated through publication in a scientific journal, which will help to share the findings with the wider healthcare community and facilitate further research and discussion in this field.
TRIAL REGISTRATION DETAILS: The protocol for this scoping review is registered with Open Science Framework, available at DOI 10.17605/OSF.IO/R3Y8U.
Fulltext Effect of Dabigatran on Clotting Time in the Clotpro Ecarin Clotting Assay: A Prospective, Single-Arm, Open-Label Study

Fong AYY, Tiong LL, Tan SSN, Geruka D, Apil GG, Choo CW, et al.

Clin Appl Thromb Hemost, 2020 12 8;26:1076029620972473.
PMID: 33284050 DOI: 10.1177/1076029620972473

Routine coagulation tests do not enable rapid, accurate determination of direct oral anticoagulant (DOAC) therapy. The ecarin clotting assay (ECA), performed on the ClotPro viscoelastic testing device, may enable sensitive and specific detection of dabigatran. We assessed the association between trough plasma dabigatran concentration and clotting time (CT) in the ClotPro ECA, in patients with non-valvular atrial fibrillation (NVAF). Each patient provided a single venous blood sample, ∼1 hour before dabigatran dosing. The study included 118 patients, of whom 64 were receiving dabigatran 110 mg twice daily and 54 were receiving 150 mg twice daily. ECA CT was moderately correlated with trough plasma dabigatran concentration (r = 0.80, p < 0.001). Slight trends toward increased plasma dabigatran concentration and prolonged ECA CT were apparent with 150 mg versus the 110 mg dose (differences not statistically significant). Individuals with creatinine clearance below 50 mL/minute had significantly higher plasma dabigatran concentrations and significantly prolonged ECA CT versus those with creatinine clearance ≥50 mL/minute. In conclusion, this preliminary study has demonstrated that CT in the ClotPro ECA reflects the plasma concentration of dabigatran in patients with NVAF. The ECA could potentially be used to assess the impact of dabigatran on a patient's coagulation status.
Prevalence of true resistant hypertension in those referred for uncontrolled hypertension in Malaysia: A comparison using different definitions

Yeo JJP, Yeo LS, Tan SSN, Delailah DDRA, Lee SWH, Hu ATH, et al.

Hypertens Res, 2024 Feb;47(2):352-357.
PMID: 37673957 DOI: 10.1038/s41440-023-01418-4

Resistant hypertension is a well-recognised clinical challenge. However, the definition and epidemiology of true resistant hypertension (RH) are less understood, especially in Asia. This cross-sectional study examined the prevalence of RH referred from primary care clinics based on various guidelines. RH was defined as blood pressure (BP) being above the threshold using ambulatory blood pressure monitoring despite adequate lifestyle measures and optimal treatment with ≥3 medications at maximally tolerated doses. Between one in four (n = 94, 24.0% using Malaysian guidelines) and up to two-thirds (n = 249, 63.7% using 2018 American guidelines) of adults referred for uncontrolled hypertension met the criteria of true RH. Of those with RH, a further one-quarter (n = 26, 26.6%) were deemed to have refractory hypertension (elevated BP despite treatment with at least 5 antihypertensive medications). Adults with RH were generally younger, more likely to be male, had a higher BMI and were more likely to have gout, CKD, and angina compared to those with controlled hypertension. The prevalence of RH amongst Asian adults with poor hypertension control is high. A concerted effort is needed to reduce the high burden of RH, especially among this population.
Association of CYP2C19*2 polymorphism with clopidogrel response and 1-year major adverse cardiovascular events in a multiethnic population with drug-eluting stents

Tan SSN, Fong AYY, Mejin M, Gerunsin J, Kong KL, Chin FYY, et al.

Pharmacogenomics, 2017 08;18(13):1225-1239.
PMID: 28745576 DOI: 10.2217/pgs-2017-0078

BACKGROUND: Patients undergoing elective percutaneous coronary intervention (PCI) with drug-eluting stents (DES) who have impaired clopidogrel response, have a higher risk of subsequent major adverse cardiovascular events (MACE).
AIM OF THE STUDY: To establish the relationship between CYP2C19 genotype, clopidogrel responsiveness and 1-year MACE.
MATERIALS & METHODS: Aspirin/clopidogrel responses were assessed with Multiplate Analyzer and CYP2C19*2 allele by SpartanRx.
RESULTS: A total of 42.0% carried ≥1 CYP2C19*2 allele. Prevalences of aspirin and clopidogrel high on-treatment platelet reactivity (HPR; local cutoffs: 300 AU*min for aspirin and 600 AU*min for clopidogrel) were 11.5% and 19.8% respectively. In multivariate ana-lysis, clopidogrel HPR was found to be an independent predictor for 1-year MACE (adj HR: 3.48, p = 0.022 ).
CONCLUSION: Having clopidogrel HPR could be a potentially modifiable risk factor guided by phenotyping.