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  1. Kow CS, Ramachandram DS, Hasan SS
    Med Clin (Barc), 2022 Nov 11;159(9):e61.
    PMID: 35933189 DOI: 10.1016/j.medcli.2022.05.016
    Matched MeSH terms: Warfarin/therapeutic use
  2. Koh KH, Tan C, Tan S, Ngu L
    Nephrology (Carlton), 2009 Sep;14(6):622.
    PMID: 19712262 DOI: 10.1111/j.1440-1797.2008.01001.x
    Matched MeSH terms: Warfarin/therapeutic use
  3. Hassan Y, Awaisu A, Aziz NA, Ismail O
    Pharm World Sci, 2005 Feb;27(1):16-9.
    PMID: 15861930
    Phenytoin has been reported to have major interactions with warfarin. Phenytoin induces warfarin's metabolism. However, there are many case reports which provide conflicting conclusions. Here, we report a case of a 65-year-old man with mechanical heart valve on chronic warfarin therapy who experienced persistent fluctuations of INR and bleeding secondary to probable warfarin-phenytoin interactions. The patient's anticoagulation clinic visits prior to hospitalization were thoroughly evaluated and we continued to follow-up the case for 3 months post-hospitalization. The reported interaction could be reasonably explained from the chronology of events and the pattern of INR fluctuations whenever phenytoin was either added or discontinued from his drug regimen.
    Matched MeSH terms: Warfarin/therapeutic use
  4. Syn NL, Wong AL, Lee SC, Teoh HL, Yip JWL, Seet RC, et al.
    BMC Med, 2018 07 10;16(1):104.
    PMID: 29986700 DOI: 10.1186/s12916-018-1093-8
    BACKGROUND: Genotype-guided warfarin dosing has been shown in some randomized trials to improve anticoagulation outcomes in individuals of European ancestry, yet its utility in Asian patients remains unresolved.

    METHODS: An open-label, non-inferiority, 1:1 randomized trial was conducted at three academic hospitals in South East Asia, involving 322 ethnically diverse patients newly indicated for warfarin (NCT00700895). Clinical follow-up was 90 days. The primary efficacy measure was the number of dose titrations within the first 2 weeks of therapy, with a mean non-inferiority margin of 0.5 over the first 14 days of therapy.

    RESULTS: Among 322 randomized patients, 269 were evaluable for the primary endpoint. Compared with traditional dosing, the genotype-guided group required fewer dose titrations during the first 2 weeks (1.77 vs. 2.93, difference -1.16, 90% CI -1.48 to -0.84, P warfarin therapy, a pharmacogenetic algorithm meets criteria for both non-inferiority and superiority in reducing dose titrations compared with a traditional dosing approach, and performs well in prediction of actual maintenance doses. These findings imply that clinicians may consider applying a pharmacogenetic algorithm to personalize initial warfarin dosages in Asian patients.

    TRIAL REGISTRATION: ClinicalTrials.gov NCT00700895 . Registered on June 19, 2008.

    Matched MeSH terms: Warfarin/therapeutic use*
  5. Kow CS, Sunter W, Bain A, Zaidi STR, Hasan SS
    Am J Cardiovasc Drugs, 2020 Aug;20(4):301-309.
    PMID: 32458370 DOI: 10.1007/s40256-020-00415-z
    Many healthcare resources have been and continue to be allocated to the management of patients with COVID-19. Therefore, the ongoing care of patients receiving oral anticoagulation with warfarin is likely to be compromised amid this unprecedented crisis. This article discusses a stepwise algorithm for the management of outpatient warfarin therapy. Alternative management strategies are presented and discussed, including alternative pharmacological therapy options and self-monitoring. Our algorithm aims to help clinicians safely optimize the treatment of patients requiring anticoagulation therapy in the context of the global response to the current pandemic.
    Matched MeSH terms: Warfarin/therapeutic use*
  6. Che Yaakob CA, Dzarr AA, Ismail AA, Zuky Nik Lah NA, Ho JJ
    PMID: 20556784 DOI: 10.1002/14651858.CD007801.pub2
    BACKGROUND: Thromboembolic complications are much higher in pregnancy due to procoagulant changes. Heparin does not cross the placenta and the use of unfractionated heparin (UFH) is the current established practice in prophylaxis and treatment for thromboembolism in pregnancy.

    OBJECTIVES: To compare the effectiveness of anticoagulant therapies for the treatment of deep vein thrombosis in pregnancy. The anticoagulant drugs included are UFH, low molecular weight heparin (LMWH) and warfarin.

    SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (March 2010) and reference lists of retrieved studies.

    SELECTION CRITERIA: Randomised controlled trials comparing any combination of warfarin, UFH, LMWH and placebo in pregnant women.

    DATA COLLECTION AND ANALYSIS: We used methods described in the Cochrane Handbooks for Systemic Reviews of Interventions for assessing the eligibility of studies identified by the search strategy. A minimum of two review authors independently assessed each study.

    MAIN RESULTS: We did not identify any eligible studies for inclusion in the review.We identified three potential studies; after assessing eligibility, we excluded all three as they did not meet the prespecified inclusion criteria. One study compared LMWH and UFH in pregnant women with previous thromboembolic events and, for most of these women, anticoagulants were used as thromboprophylaxis. There were only three women who had a thromboembolic event during the current pregnancy and it was unclear whether the anticoagulant was used as therapy or prophylaxis. We excluded one study because it included only women undergoing caesarean birth. The third study was not a randomised trial.

    AUTHORS' CONCLUSIONS: There is no evidence from randomised controlled trials on the effectiveness of anticoagulation for deep vein thrombosis in pregnancy. Further studies are required.

    Matched MeSH terms: Warfarin/therapeutic use
  7. Yap SH, Ng YP, Roslan A, Kolanthaivelu J, Koh KW, P'ng HS, et al.
    Med J Malaysia, 2017 12;72(6):360-364.
    PMID: 29308774 MyJurnal
    INTRODUCTION: Atrial fibrillation (AF) is the most common cardiac arrhythmia with significant morbidity and mortality in relation to thromboembolic stroke. Our study aimed to evaluate the safety and efficacy of dabigatran in stroke prevention in elderly patient with nonvalvular AF with regard to the risk of ischemic stroke and intracranial haemorrhage (ICH) in real-world setting.

    METHODS: A retrospective cohort study of 200 patients on dabigatran and warfarin from January 2009 till September 2016 was carried out. Data were collected for 100 patients on dabigatran and 100 patients on warfarin.

    RESULTS: The mean follow-up period was 340.7±322.3 days for dabigatran group and 410.5±321.2 days for warfarin group. The mean time in therapeutic range (TTR) was 52±18.7%. The mean CHA2DS2 -VASc score for dabigatran group was 4.4±1.1 while 5.0±1.5 for warfarin group. None in dabigatran group experienced ischemic stroke compared to one patient in warfarin group (p=0.316). There was one patient in dabigatran group suffered from ICH compared to none in warfarin group (p=0.316). Four patients in warfarin group experienced minor bleeding, while none from dabigatran group (p=0.043).

    CONCLUSION: Overall bleeding events were significantly lower in dabigatran group compared to warfarin group. In the presence of suboptimal TTR rates and inconveniences with warfarin therapy, non-vitamin-K antagonist oral anticoagulants (NOAC) are the preferred agents for stroke prevention in elderly Asian patients for nonvalvular AF.

    Matched MeSH terms: Warfarin/therapeutic use*
  8. Jin-Poi T, Shatriah I, Ng SL, Zurkurnai Y, Yunus R
    JAMA Ophthalmol, 2013 Feb;131(2):263-5.
    PMID: 23411903 DOI: 10.1001/jamaophthalmol.2013.587
    Matched MeSH terms: Warfarin/therapeutic use
  9. Ng DL, Malik NMBA, Chai CS, Goh GM, Tan SB, Bee PC, et al.
    Health Qual Life Outcomes, 2020 Oct 20;18(1):347.
    PMID: 33081816 DOI: 10.1186/s12955-020-01600-z
    BACKGROUND: The use of warfarin in patients with non-valvular atrial fibrillation (NVAF) can be challenging. In this study, we evaluate the time in therapeutic range (TTR), health-related quality of life (HRQoL) and treatment satisfaction of patients on long-term warfarin for NVAF. The HRQoL and treatment satisfaction were compared based on the TTR.

    METHODS: A cross-sectional study was conducted among patients on warfarin for NVAF who attended the anticoagulant clinic of a tertiary cardiology referral center in Sarawak from 1st June 2018 to 31st May 2019. Patients' TTR was calculated by using Rosendaal technique, while their HRQoL and treatment satisfaction were assessed by using Short Form 12 Health Survey version 2 (SF12v2) and Duke Anticoagulant Satisfaction Scale (DASS), respectively.

    RESULTS: A total of 300 patients were included, with mean TTR score of 47.0 ± 17.3%. The physical component summary (PCS) and mental component summary (MCS) score of SF-12v2 were 47.0 ± 9.0 and 53.5 ± 9.6, respectively. The total score for DASS was 55.2 ± 21.3, while the score for limitations (L), hassles and burdens (H&B) and positive psychological impacts (PPI) were 18.0 ± 10.0, 15.6 ± 9.1 and 21.6 ± 5.9, respectively. Seventy-three (24.3%) patients had good TTR (≥ 60%), with mean of 70.2 ± 8.7%; while 227 (75.5%) patients with poor TTR had significantly lower mean of 39.5 ± 11.9% (p = 0.006). There was no significant difference in the score of PCS (p = 0.150), MCS (p = 0.919) and each domain of SF-12v2 (p = 0.184-0.684) between good and poor TTR, except for social functioning (p = 0.019). The total DASS score was also not significantly different between group (p = 0.779). Similar non-significant difference was also reported in all the DASS sub dimensions (p = 0.502-0.699).

    CONCLUSIONS: Majority of the patients on long-term warfarin for NVAF in the current study have poor TTR. Their HRQoL and treatment satisfaction are independent of their TTR. Achieving a good TTR do not compromise the HRQoL and treatment satisfaction. Therefore, appropriate measures should be taken to optimise INR control, failing which direct oral anticoagulant therapy should be considered.

    Matched MeSH terms: Warfarin/therapeutic use*
  10. Lee SC, Ng SS, Oldenburg J, Chong PY, Rost S, Guo JY, et al.
    Clin. Pharmacol. Ther., 2006 Mar;79(3):197-205.
    PMID: 16513444
    Chinese and Malay subjects have been reported to require less maintenance warfarin than Indians that could not be accounted for by cytochrome P450 (CYP) 2C9 variants. Vitamin K epoxide reductase complex 1 (VKORC1) is the target enzyme of warfarin, and VKORC1 intronic variants and haplotypes have recently been shown to influence VKORC1 activity and warfarin requirements.
    Matched MeSH terms: Warfarin/therapeutic use
  11. Ng SS, Lai NM, Nathisuwan S, Chaiyakunapruk N
    Clin Drug Investig, 2018 Jul;38(7):579-591.
    PMID: 29569095 DOI: 10.1007/s40261-018-0641-5
    INTRODUCTION: Anticoagulation therapy is the fundamental approach for stroke prevention in atrial fibrillation (AF) patients. Numerous systematic reviews comparing anticoagulation strategies have been published. We aim to summarize the efficacy and safety evidence of these strategies in AF patients from previously published systematic reviews.

    METHODS: We searched PubMed, EMBASE and Cochrane library from inception to Feb 24th, 2017, to identify systematic reviews and meta-analyses of randomized controlled trials that assessed interventions or strategies to improve oral anticoagulant use in AF patients.

    RESULTS: Thirty-four systematic reviews were eligible for inclusion but only 11 were included in the qualitative analyses, corresponding to 40 unique meta-analyses, as the remaining systematic reviews had overlapping primary studies. There was insufficient evidence to support the efficacy of genotype-guided dosing and pharmacist-managed anticoagulation clinics for stroke prevention in AF patients. Conversely, patient's self-management and novel oral anticoagulants (NOACs), in general were superior to warfarin for preventing stroke and reducing mortality. All interventions showed comparable risk of major bleeding with warfarin.

    CONCLUSION: Findings from this overview support the superiority of NOACs and patient's self-management for preventing stroke in AF patients. However, uncertainties remain on the benefits of genotype-guided dosing and pharmacist-managed anticoagulation clinics due to poor quality evidence, and future research is warranted.

    Matched MeSH terms: Warfarin/therapeutic use
  12. Lu HT, Nordin R, Othman N, Choy CN, Kam JY, Leo BC, et al.
    J Med Case Rep, 2016 Aug 10;10(1):221.
    PMID: 27510438 DOI: 10.1186/s13256-016-1018-0
    BACKGROUND: Many cases of cardiac masses have been reported in the literature, but in this case report we described a rare case of biatrial cardiac mass that represented a challenge for diagnosis and therapy. The differentiation between cardiac masses such as thrombi, vegetations, myxomas and other tumors is not always straightforward and an exact diagnosis is important because of its distinct treatment strategy. Transthoracic/esophageal echocardiography and cardiac magnetic resonance play an important role in establishing the diagnosis of cardiac masses. However, no current noninvasive diagnostic tool has the ability to absolutely diagnose cardiac masses; obtaining a pathological specimen by surgical resection of cardiac masses is the only reliable method to diagnose cardiac masses accurately. Our case report is an exception in that the final diagnosis was affirmed by empirical anticoagulation therapy based on clinical judgment and noninvasive characterization of biatrial mass.

    CASE PRESENTATION: We described a 54-year-old Malay man with severe mitral stenosis and atrial fibrillation who presented with a biatrial mass. Transthoracic/esophageal echocardiography and cardiac magnetic resonance detected a large, homogeneous right atrial mass typical of a thrombus, and a left atrial mass adhering to interatrial septum that mimicked atrial myxoma. The risk factors, morphology, location, and characteristics of the biatrial cardiac mass indicated a diagnosis of thrombi. However, our patient declined surgery. As a result, the nature of his cardiac masses was not specified by histology. Of note, his left atrial mass was completely regressed by long-term warfarin, leaving a residual right atrial mass. Thus, we affirmed the most probable diagnosis of cardiac thrombi. During the course of treatment, he had an episode of non-fatal ischemic stroke most probably because of a thromboembolism.

    CONCLUSIONS: Noninvasive characterization of cardiac mass is essential in clarifying the diagnosis and directing treatment strategy. Anticoagulation is a feasible treatment when the clinical assessment, risk factors, and imaging findings indicate a diagnosis of thrombi. After prolonged anticoagulation therapy, complete resolution of biatrial thrombi was achievable in our case.

    Matched MeSH terms: Warfarin/therapeutic use*
  13. Ngow H, Teh LK, Langmia IM, Lee WL, Harun R, Ismail R, et al.
    Xenobiotica, 2008 Jun;38(6):641-51.
    PMID: 18570163 DOI: 10.1080/00498250801999087
    1. A retrospective study was conducted to explore the importance of CYP2C9 genotyping for the initiation and maintenance therapy of warfarin in clinical practice. A total of 191 patients on warfarin therapy in a local hospital were recruited after written informed consent. Their medical records were reviewed and no intervention of warfarin dose was performed. 2. A total of 5 ml of blood were taken from each subject for DNA extraction and identification of 1, 2, 3 and 4 CYP2C9 alleles, using a nested-allele-specific-multiplex-polymerase chain reaction (PCR). Half the patients were Malays and the remaining were Chinese. 3. Two genotypes were detected; 93.2% had CYP2C9 1/1 and 6.8% were CYP2C9 1/3. Warfarin doses were higher in patients with CYP2C91/1. Patients with the 1/3 genotype experienced a higher rate of serious and life-threatening bleeding; 15.4 versus 6.2 per 100 patients per 6 months. 4. The observation clearly highlights the inadequacy of the current dosing regimens and the need to move toward a more individualized approach to warfarin therapy. Prospective clinical studies are now being conducted to assess dosing algorithms that incorporate the contribution of the genotype to allow the individualization of warfarin dose.
    Matched MeSH terms: Warfarin/therapeutic use
  14. Thanimalai S, Shafie AA, Hassali MA, Sinnadurai J
    Int J Clin Pharm, 2013 Oct;35(5):736-43.
    PMID: 23715759 DOI: 10.1007/s11096-013-9796-6
    BACKGROUNDS: Limited evidence is available regarding pharmacist managed anticoagulation clinic in the Southeast Asian region where there is marked difference in terms of care model, genetic composition and patient demographics.

    OBJECTIVES: This study aimed at comparing the anticoagulation clinic managed by the pharmacist with physician advisory and the usual medical care provided in Kuala Lumpur Hospital (KLH) in terms of anticoagulation control and adverse outcomes.

    SETTING: A 2,302 bedded government tertiary referral hospital in Malaysia.

    METHODS: A 6-month retrospective cohort study of the effectiveness of two models of anticoagulation care, the pharmacist managed anticoagulation clinic which is known as warfarin medication therapy adherence clinic (WMTAC) and usual medical clinic (UMC) in KLH was conducted, where a random number generator was used to recruit patients. The UMC patients received standard medical care where they are managed by rotational medical officers in the physicians' clinic. As for the WMTAC with physician advisory, the pharmacist will counsel and review the patients internationalised normalization ratio at each clinic visit and also adjust the patients' warfarin dose accordingly. Patients are referred to physicians if immediate attention is required.

    MAIN OUTCOME MEASURE: The main therapeutic outcome is time in therapeutic range (TTR) both actual and expanded TTR and thromboembolic and bleeding complications.

    RESULTS: Each of the WMTAC and usual medical care recruited 92 patients, which totals to 184 patients. The patient demographics in terms of age, race and indication of treatment were comparable. At the end of the 6 months follow-up, patients in the WMTAC group had significantly higher actual-TTR (65.1 vs. 48.3 %; p < 0.05) compared to those in usual medical care group. Rates of admission were 6.5 versus 28.2 events per 100 person-years for the WMTAC and UMC groups, respectively. Though the bleeding incidences were not significantly different, it was reduced.

    CONCLUSIONS: These findings will impact local warfarin patient management services and policies because there was no available evidence supporting the role of pharmacists in the management of warfarin patients prior to this study.
    Matched MeSH terms: Warfarin/therapeutic use
  15. Abdullah WZ, Roshan TM, Hussin A, Zain WS, Abdullah D
    Blood Coagul Fibrinolysis, 2013 Dec;24(8):893-5.
    PMID: 24030118 DOI: 10.1097/MBC.0b013e3283642ee2
    Treatment with thalidomide is associated with vascular thrombosis. The effect of thalidomide on platelet activation is unclear, although the use of aspirin is justified for thromboprophylaxis. A study on platelet activation markers was done among multiple myeloma patients receiving thalidomide therapy with warfarin as thromboprophylaxis. Strict criteria and procedure were set to avoid misinterpretation of platelet activation other than due to the thalidomide's effect. Blood specimen pre and post thalidomide therapy were used for flow cytometric analysis. Platelet surface P-selectin, CD62P expression and PAC-1 (antibody that recognizes conformational change of the GPIIb/IIIa complex) were examined by using three-colour flowcytometer. Increased expression marker for PAC-1 was observed after 4 weeks of thalidomide treatment (P 
    Matched MeSH terms: Warfarin/therapeutic use
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