Initiation of warfarin therapy in elderly medical inpatients: A safe and accurate regimen

Siguret, Virginie; Gouin, I.; Debray, Matthieu; Perret‐Guillaume, Christine; Boddaert, Jacques; Mahé, Isabelle; Donval, Valérie; Seux, Marie-Laure; Romain-Pilotaz, Marjolaine; Gisselbrecht, Mathilde; Verny, Marc; Pautas, Éric

doi:10.1016/j.amjmed.2004.07.053

Cited by 90 publications

(52 citation statements)

References 27 publications

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“…35 In addition, our definition of therapeutic dose was ad hoc as definitions vary among studies. 4,8,11,21,22 Our definition was appropriate for orthopedic patients who tend to use warfarin for a limited timeframe. A final minor limitation was that only 19 patients were taking a statin and only 1 was taking amiodarone, so we had inadequate statistical power to determine how these, and other drugs that interact with warfarin, affected warfarin dose.…”

Section: Discussionmentioning

confidence: 99%

“…For either strategy, the actual maintenance dose is eventually found through a process of trial and error as the starting dose is adjusted according to the INR value-often starting on the third or fourth day of therapy. 9,21,22,28 Our results demonstrate that the INR response is only one of several factors that should be used to estimate the therapeutic dose in orthopedic patients: the accuracy of dose refinements based solely on INR is inherently limited, heightening the chance of excessive or inadequate warfarin dose adjustments.After INR response, the next variable to enter the stepwise regression was the initial warfarin dose, which explained 20.3% of the variability in therapeutic dose. This finding is interesting because 34 (37%) of the included patients were given initial doses that did not take VKORC1 genotype into account, while the remainder received genetically tailored doses.…”

mentioning

confidence: 99%

“…4 The purpose of this study was to develop a dose-refinement nomogram to guide clinicians in adjusting warfarin doses. This nomogram would be similar to prior algorithms, 21,22 but will have 2 advantages: (1) it will allow for, but not require, a first dose that is tailored to clinical and/or genetic factors and (2) it will incorporate genetics and clinical factors that are independent predictors of how much the dose should be refined. 1,11 If successful, the proposed warfarin nomogram would simplify and standardize warfarin initiation.…”

Section: Introductionmentioning

confidence: 99%

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Genetic-based dosing in orthopedic patients beginning warfarin therapy

Millican

Lenzini

Milligan

et al. 2007

Blood

159

139

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IntroductionWarfarin sodium is characterized by a narrow therapeutic range (eg, an international normalized ratio [INR]) of 2.0-3.0), a marked interindividual variation in dosing requirements, and an increased risk of adverse events when the dose is too high or low. 1,2 To minimize the high incidence of such events, [3][4][5] particularly during the first few weeks of initiating therapy, 1,6 most guidelines recommend prescribing warfarin at or near the anticipated maintenance dose and then adjusting the dose by trial and error. 1,7,8 While algorithms for predicting this maintenance dose a priori have improved, [9][10][11][12][13][14][15][16] there remains little guidance on how this starting dose should be adjusted a posteriori based on the subsequent INR values. We hypothesized that use of genetic markers could help optimize these dose refinements.Two common single nucleotide polymorphisms (SNPs) in the cytochrome P450 (CYP) 2C9 system are associated with impaired metabolism of warfarin, [3][4][5][6]11,17 while SNPs in the gene for vitamin K epoxide reductase complex 1 (VKORC1) correlate with warfarin sensitivity and resistance. 2,[18][19][20] No prior study has examined the impact of these SNPs on warfarin-dose adjustments. Given the current knowledge about these markers, we hypothesize that for a given INR, a patient who is a slow metabolizer of warfarin may need a more cautious adjustment in their dose than a similar patient who is a normal metabolizer. Failure to tailor dose refinements during warfarin induction in poor metabolizers may have contributed to the 3-fold increased risk of (laboratory or clinical) adverse events among poor metabolizers in our initial prospective study of pharmacogenetic-based warfarin therapy. 4 The purpose of this study was to develop a dose-refinement nomogram to guide clinicians in adjusting warfarin doses. This nomogram would be similar to prior algorithms, 21,22 but will have 2 advantages: (1) it will allow for, but not require, a first dose that is tailored to clinical and/or genetic factors and (2) it will incorporate genetics and clinical factors that are independent predictors of how much the dose should be refined. 1,11 If successful, the proposed warfarin nomogram would simplify and standardize warfarin initiation. Patients, materials, and methodsThe study was a retrospective analysis of 2 cohorts of orthopedic surgery patients who had participated in 2 prospective studies of pharmacogeneticbased warfarin therapy. The Human Research Protection Office at Washington University Medical Center approved these studies. PatientsFor patients in both cohorts, we offered participation if they were scheduled for primary or revision total knee or hip arthroplasty at Washington University Medical Center and if they were 18 years or older. We excluded patients who had previously taken warfarin or who had contraindications to warfarin treatment. To allow time for genotyping, we also excluded patients scheduled for surgery fewer than 7 days following referral to our anticoagulation s...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Genetic-based dosing in orthopedic patients beginning warfarin therapy

Millican

Lenzini

Milligan

et al. 2007

Blood

159

139

View full text Add to dashboard Cite

show abstract

“…2,6,7 In a previous study, a warfarin induction algorithm specifically designed for elderly inpatients and based on the international normalized ratio (INR) measured after three daily intakes of 4 mg was validated. 8 Rules were then developed for adjusting warfarin dosages after Day 3. These induction and adjustment guidelines were included in a computer program for assisting in warfarin dosage selection in elderly inpatients.…”

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confidence: 99%

Improving Anticoagulation Control in Hospitalized Elderly Patients on Warfarin

Gouin‐Thibault

Lévy

Pautas

et al. 2010

J American Geriatrics Society

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OBJECTIVES:To determine the effect of patient characteristics and of specific guidelines that were developed for managing warfarin therapy in older adults and included in an in-house computer program on anticoagulation quality. DESIGN: Thirteen-month observational study. SETTING: Acute care, extended care, and rehabilitation geriatric wards of a teaching hospital in Paris, France. PARTICIPANTS: Hospitalized patients (N 5 307, mean age 86.1 AE 6.1) treated with warfarin with a therapeutic international normalized ratio range of 2.0 to 3.0. INTERVENTION: Patients were assigned according to care unit to the computer-generated dosing group (CGD) or the standard management group (SM; usual physician-based care). MEASUREMENTS: Relationships between anticoagulation quality criteria and covariates (age, sex, warfarin indication, treatment phase, follow-up duration, model of care). RESULTS: According to multivariate analysis, only model of care and follow-up duration independently influenced anticoagulation control; the proportion of time within therapeutic INR range 2.0 to 3.0 was significantly greater in the CGD group than in the SM group (59% vs 48%, P 5.004). When a wider INR range was analyzed (1.8-3.2), the proportion of time within range was 73% versus 64% (P 5.006). Use of the computer was associated with fewer days with INRs greater than 3, a smaller percentage of INRs of 4 or greater, a longer time to the first INR of 4.0 or greater, and a smaller mean number of INRs per month than SM (all Po.01). CONCLUSION: Initiation regimen and long-term rules that have specifically been developed and included in a computerized dosage program improve quality of anticoagulation in elderly inpatients, allowing them to benefit from a quality of care as high as that of younger ambulatory patients. J Am Geriatr Soc 58:242-247, 2010.

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“…In clinical and pharmacogenetic models for predicting maintenance dose, age is associated with lower dose requirements [77]. Low dose VKA initiation algorithms have been suggested in the elderly to reduce bleeding complications [78] as the initial phase of AC is the period at highest haemorrhagic risk [79]. Several bleeding scores have been developed in the setting of VTE [80][81][82][83], but a recently published analysis on patients from the Swiss national VTE cohort showed poor performance of all these scores in patients N65 years (area under the ROC curves ranging from 0.49 to 0.6) [84].…”

Section: Managing the Switch To Vkas In Elderly Patients With Pementioning

confidence: 99%

Diagnosis and management of pulmonary embolism in the elderly

Robert‐Ebadi

Righini

2014

European Journal of Internal Medicine

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a b s t r a c t a r t i c l e i n f oElderly patients are a population not only at particularly high risk of venous thromboembolism including pulmonary embolism (PE), but also at high risk of adverse clinical outcomes and treatment-related complications. Major progresses have been achieved in the diagnosis and treatment of PE over the last two decades. Nevertheless, some of elderly patients' specificities still represent important challenges in the management of PE in this population, from its suspicion to its diagnosis and treatment, and are discussed in this review. Perspectives for the future are from a diagnostic point of view the potential implementation of age-adjusted D-dimer cut-offs that will allow ruling out PE in a greater proportion of elderly patients without the need for thoracic imaging. From a therapeutic point of view, acquisition of post-marketing clinical experience with the use of new oral anticoagulants is still necessary, and in the meantime, these drugs should be prescribed with great caution in thoroughly selected elderly patients.

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Initiation of warfarin therapy in elderly medical inpatients: A safe and accurate regimen

Cited by 90 publications

References 27 publications

Genetic-based dosing in orthopedic patients beginning warfarin therapy

Genetic-based dosing in orthopedic patients beginning warfarin therapy

Improving Anticoagulation Control in Hospitalized Elderly Patients on Warfarin

Diagnosis and management of pulmonary embolism in the elderly

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