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Comparing effectiveness of two anticoagulation management models in a Malaysian tertiary hospital

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/administration & dosage*
Fulltext Pulmonary embolectomy in heparin-induced thrombocytopenia and thrombosis? Safety of heparin use

Sachithanandan A

Interact Cardiovasc Thorac Surg, 2010 Nov;11(5):681.
PMID: 20962169 DOI: 10.1510/icvts.2010.247460A
Matched MeSH terms: Warfarin/administration & dosage
Plasma Metabolites as Predictors of Warfarin Outcome in Atrial Fibrillation

Bawadikji AA, Teh CH, Sheikh Abdul Kader MAB, Abdul Wahab MJB, Syed Sulaiman SA, Ibrahim B

Am J Cardiovasc Drugs, 2020 Apr;20(2):169-177.
PMID: 31435902 DOI: 10.1007/s40256-019-00364-2

BACKGROUND: Warfarin is prescribed as an oral anticoagulant to treat/prevent thromboembolism in conditions such as atrial fibrillation. As there is a narrow therapeutic window, treatment with warfarin is challenging. Pharmacometabonomics using nuclear magnetic resonance (NMR) spectroscopy may provide novel techniques for the identification of novel biomarkers of warfarin.
PURPOSE: The aim was to determine the metabolic fingerprint that predicts warfarin response based on the international normalized ratio (INR) in patients who are already receiving warfarin (phase I: identification) and to ascertain the metabolic fingerprint that discriminates stable from unstable INR in patients starting treatment with warfarin (phase II: validation).
EXPERIMENTAL APPROACH: A total of 94 blood samples were collected for phase I: 44 patients with stable INR and 50 with unstable INR. Meanwhile, 23 samples were collected for phase II: nine patients with stable INR and 14 with unstable INR. Data analysis was performed using multivariate analysis including principal component analysis and partial least square-discriminate analysis (PLS-DA), followed by univariate and multivariate logistic regression (MVLR) to develop a model to identify unstable INR biomarkers.
KEY RESULTS: For phase I, the PLS-DA model showed the following results: sensitivity 93.18%, specificity 91.49% and accuracy 92.31%. In the MVLR analysis of phase I, ten regions were associated with unstable INR. For phase II, the PLS-DA model showed the following results: sensitivity 66.67%, specificity 61.54% and accuracy 63.64%.
CONCLUSIONS AND IMPLICATIONS: We have shown that the pharmacometabonomics technique was able to differentiate between unstable and stable INR with good accuracy. NMR-based pharmacometabonomics has the potential to identify novel biomarkers in plasma, which can be useful in individualizing treatment and controlling warfarin side effects, thus, minimizing undesirable effects in the future.

Matched MeSH terms: Warfarin/administration & dosage
Contribution of VKORC1 and CYP2C9 polymorphisms in the interethnic variability of warfarin dose in Malaysian populations

Gan GG, Phipps ME, Lee MM, Lu LS, Subramaniam RY, Bee PC, et al.

Ann Hematol, 2011 Jun;90(6):635-41.
PMID: 21110192 DOI: 10.1007/s00277-010-1119-6

Within the Asian populations, Indian patients had been reported to require higher warfarin dose compared with the Chinese and Malay patients, and this could not entirely be explained by cytochrome P450 (CYP)2C9 gene variants. Genetic variants of vitamin K epoxide oxidase reductase complex subunit 1 (VKORC1) has been well established as one of key determinants in the different responses of warfarin amongst patients. Adult patients who attended an anticoagulation clinic with stable INR were recruited. VKORC1 and CYP2C9 genotype were sequenced, and clinical characteristics were assessed. A total of 91 Malays, 96 Chinese, and 46 Indian patients were recruited. The mean age was 55 years and 51.5% were males. The mean dose of warfarin for all patients was 3.7 mg, and the mean daily dose of warfarin was significantly higher in Indians compared with the Chinese and Malay patients, 4.9 versus 3.5 and 3.3 mg, respectively (p warfarin dose in patients with GG genotype required a significant higher warfarin dose compared with those with AG and AA genotype (4.9 vs. 3.7 vs. 3.1 mg, respectively; p warfarin dose. In conclusion, VKORC1 and CYP2C9 polymorphism contribute to the difference dose requirement amongst the patients but other additional possible factors may play a role in the Indian race.
Study site: Anticoagulation clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia

Matched MeSH terms: Warfarin/administration & dosage*