A multi-component intervention to prevent major bleeding in older patients receiving warfarin. A randomised, controlled trial

Baylor College of Medicine, Section of Health Services Research, Houston Center for Quality of Care and Utilization Studies, Veterans Affairs Medical Center (152), Building 110T, 2002 Holcombe Boulevard, Houston, TX 77030, USA.
Annals of internal medicine (Impact Factor: 17.81). 11/2000; 133(9):687-95.
Source: PubMed


Warfarin is effective in the treatment and prevention of many venous thromboembolic disorders, but it often leads to bleeding.
To develop a multicomponent program of management of warfarin therapy and to determine its effect on the frequency of warfarin-related major bleeding in older patients.
Randomized, controlled trial.
University hospital in Cleveland, Ohio.
325 patients 65 years of age or older who started warfarin therapy during hospitalization.
Patients were stratified according to baseline risk for major bleeding and were randomly assigned to receive the intervention (n = 163) or usual care (n = 162) by their primary physicians for 6 months. The intervention consisted of patient education about warfarin, training to increase patient participation, self-monitoring of prothrombin time, and guideline-based management of warfarin dosing.
Major bleeding, death, recurrent venous thromboembolism, and therapeutic control of anticoagulant therapy at 6 months.
In an intention-to-treat analysis, major bleeding was more common at 6 months in the usual care group than in the intervention group (cumulative incidence, 12% vs. 5.6%; P = 0.0498, log-rank test). The most frequent site of major bleeding in both groups was the gastrointestinal tract. Death and recurrent venous thromboembolism occurred with similar frequency in both groups at 6 months. Throughout 6 months, the proportion of total treatment time during which the international normalized ratio was within the therapeutic range was higher in the intervention group than in the usual care group (56% vs. 32%; P < 0.001). After 6 months, major bleeding occurred with similar frequencies in the intervention and usual care groups.
A multicomponent comprehensive program of warfarin management reduced the frequency of major bleeding in older patients. Although the generalizability and cost-effectiveness of this program remain to be demonstrated, these findings support the premise that efforts to reduce the likelihood of major bleeding will lead to safe and effective use of warfarin therapy in older patients.

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    • "In this study, patients with the CYP2C9*2 and CYP2C9*3 alleles required lower doses of warfarin. This observation has since been reported in many clinical studies [115–117] and seems to be especially noticeable at the beginning of the anticoagulant treatment [118–120]. Stabilisation of treatment is also a parameter that was found to be influenced by polymorphisms of CYP2C9. "
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    ABSTRACT: Interindividual variability in drug response is a major clinical problem. Polymedication and genetic polymorphisms modulating drug-metabolising enzyme activities (cytochromes P450, CYP) are identified sources of variability in drug responses. We present here the relevant data on the clinical impact of the major CYP polymorphisms (CYP2D6, CYP2C19 and CYP2C9) on drug therapy where genotyping and phenotyping may be considered, and the guidelines developed when available. CYP2D6 is responsible for the oxidative metabolism of up to 25 % of commonly prescribed drugs such as antidepressants, antipsychotics, opioids, antiarrythmics and tamoxifen. The ultrarapid metaboliser (UM) phenotype is recognised as a cause of therapeutic inefficacy of antidepressant, whereas an increased risk of toxicity has been reported in poor metabolisers (PMs) with several psychotropics (desipramine, venlafaxine, amitriptyline, haloperidol). CYP2D6 polymorphism influences the analgesic response to prodrug opioids (codeine, tramadol and oxycodone). In PMs for CYP2D6, reduced analgesic effects have been observed, whereas in UMs cases of life-threatening toxicity have been reported with tramadol and codeine. CYP2D6 PM phenotype has been associated with an increased risk of toxicity of metoprolol, timolol, carvedilol and propafenone. Although conflicting results have been reported regarding the association between CYP2D6 genotype and tamoxifen effects, CYP2D6 genotyping may be useful in selecting adjuvant hormonal therapy in postmenopausal women. CYP2C19 is responsible for metabolising clopidogrel, proton pump inhibitors (PPIs) and some antidepressants. Carriers of CYP2C19 variant alleles exhibit a reduced capacity to produce the active metabolite of clopidogrel, and are at increased risk of adverse cardiovascular events. For PPIs, it has been shown that the mean intragastric pH values and the Helicobacter pylori eradication rates were higher in carriers of CYP2C19 variant alleles. CYP2C19 is involved in the metabolism of several antidepressants. As a result of an increased risk of adverse effects in CYP2C19 PMs, dose reductions are recommended for some agents (imipramine, sertraline). CYP2C9 is responsible for metabolising vitamin K antagonists (VKAs), non-steroidal anti-inflammatory drugs (NSAIDs), sulfonylureas, angiotensin II receptor antagonists and phenytoin. For VKAs, CYP2C9 polymorphism has been associated with lower doses, longer time to reach treatment stability and higher frequencies of supratherapeutic international normalised ratios (INRs). Prescribing algorithms are available in order to adapt dosing to genotype. Although the existing data are controversial, some studies have suggested an increased risk of NSAID-associated gastrointestinal bleeding in carriers of CYP2C9 variant alleles. A relationship between CYP2C9 polymorphisms and the pharmacokinetics of sulfonylureas and angiotensin II receptor antagonists has also been observed. The clinical impact in terms of hypoglycaemia and blood pressure was, however, modest. Finally, homozygous and heterozygous carriers of CYP2C9 variant alleles require lower doses of phenytoin to reach therapeutic plasma concentrations, and are at increased risk of toxicity. New diagnostic techniques made safer and easier should allow quicker diagnosis of metabolic variations. Genotyping and phenotyping may therefore be considered where dosing guidelines according to CYP genotype have been published, and help identify the right molecule for the right patient.
    Molecular Diagnosis & Therapy 04/2013; 17(3). DOI:10.1007/s40291-013-0028-5 · 2.89 Impact Factor
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    • "We know of only one such randomized single center study, and that showed a significant reduction in the number of thromboembolic complications in patients with a mean age of 64 to 67 over an average follow-up of one year [16]. Another trial indicated that self-testing in elderly patients may effectively reduce excessive bleeding rates [17]. Against this background, the SPOG 60+ (structured teaching and self-management program for patients who are over 60 years of age and receiving OAC) trial aimed to compare self-management with routine care in elderly patients receiving long-term anticoagulation treatment by using thromboembolic and hemorrhagic complications as the combined primary outcome. "
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    ABSTRACT: Unlabelled: BACKGROUND - RATIONALE FOR STUDY: In elderly patients, long-term self-management of oral anticoagulation has been shown to reduce the number of major thromboembolic and bleeding complications and improve the quality of oral anticoagulation (OAC) control compared to routine care for a mean follow-up period of three years. This article presents the results of the predefined secondary endpoint treatment-related quality of life (QoL). Methods and results: The effect of self-management on five aspects of QoL was evaluated in comparison with routine care. A validated questionnaire specifically designed for patients receiving OAC was used. The evaluation was possible for 141 patients, comprising 90% of surviving patients on OAC. At baseline, all patients had high scores for the following QoL-aspects: general treatment satisfaction, self-efficacy, daily hassles and strained social network. A high proportion of patients in both groups explicitly reported high distress, indicating that general psychological distress seems to be of particular concern in this population. After about 3 years of follow-up, patients performing self-management showed a significantly greater improvement in general treatment satisfaction than controls (median score increase [25th percentile, 75th percentile]: 0.9 [0.0, 1.6] vs. 0.0 [-0.2, 0.6], p=0.002; scale 1-6). Changes in general psychological distress, self-efficacy, daily hassles and strained social network were not significant. Conclusion: Treatment related quality of life in elderly patients performing self-management of OAC was similar as for patients in routine care setting, with a tendency of higher general treatment satisfaction, after three years of follow up.
    Thrombosis Research 06/2012; 130(3):e60-6. DOI:10.1016/j.thromres.2012.06.012 · 2.45 Impact Factor
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    • "Given the potential scope of IT-based resources to support patient education7,8,9,10, they can also be used to educate patients receiving more complicated treatments, such as warfarin therapy.11,12 Warfarin is a complex drug and is often associated with life-threatening adverse drug-related complications, hence patients receiving warfarin therapy require extensive education to optimize therapeutic outcomes.1,13,14,15,16 Unfortunately, to date, the provision of warfarin education to patients in different clinical settings has generally been inadequate.17,18,19 "
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    ABSTRACT: To explore healthcare professionals' views about the benefits and challenges of using information technology (IT) resources for educating patients about their warfarin therapy. A cross-sectional survey of both community and hospital-based healthcare professionals (e.g., doctors, pharmacists and nurses) involved using a purpose-designed questionnaire. The questionnaires were distributed using a multi-modal approach to maximise response rates. Of the total 300 questionnaires distributed, 109 completed surveys were received (43.3% response rate). Over half (53.2%) of the healthcare participants were aged between 40-59 years, the majority (59.5%) of whom were female. Fifty nine (54.1%) participants reported having had no access to warfarin-specific IT-based patient education resources, and a further 19 (38.0%) of the participants who had IT-access reported that they never used such resources. According to the healthcare participants, the main challenges associated with educating their patients about warfarin therapy included: patient-related factors, such as older age, language barriers, cognitive impairments and/or ethnic backgrounds or healthcare professional factors, such as time constraints. The healthcare professionals reported that there were several aspects about warfarin therapy which they found difficult to educate their patients about which is why they identified computers and interactive touch screen kiosks as preferred IT devices to deliver warfarin education resources in general practices, hospital-based clinics and community pharmacies. At the same time, the healthcare professionals also identified a number of facilitators (e.g., to reinforce warfarin education, to offer reliable and easily comprehensible information) and barriers (e.g., time and costs of using IT resources, difficulty in operating the resources) that could impact on the effective implementation of these devices in educating patients about their warfarin therapy. The findings of the study suggest that there is a need for improving healthcare professionals' use of, and access to IT-based warfarin education resources for patients. The study findings also suggest addressing the concerns raised by the healthcare professionals when implementing such IT resources successfully to help educate patients about their warfarin therapy.
    04/2012; 10(2):97-104. DOI:10.4321/S1886-36552012000200006
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