Evaluation of Warfarin Dose Requirements in Patients with Chronic Kidney Disease and End‐Stage Renal Disease

Sakaan, Sami; Hudson, Joanna Q.; Oliphant, Carrie S.; Tolley, Elizabeth A.; Cummings, Carolyn; Alabdan, Numan; Self, Timothy H.

doi:10.1002/phar.1445

Cited by 18 publications

(11 citation statements)

References 27 publications

(34 reference statements)

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“…The liver is the principle organ for the synthesis of clotting factors and metabolism of many drugs including warfarin; and if dysfunction may result in warfarin toxicity [ 20 , 41 ]. Moreover, renal failure [ 34 , 57 ], thyroid disease [ 23 ] and malignancies [ 45 ] can all complicate anticoagulation by increasing INR and bleeding tendency. Other factors that may have contributed to the unstable INR include food intake [ 12 ], failure to adhere to instructions (skipping doses or overdosing), lack of timely follow-up and dose adjustment.…”

Section: Discussionmentioning

confidence: 99%

Characteristics of patients with thromboembolic disorders on warfarin therapy in resource limited settings

Kamuren

Kigen

Keter

et al. 2018

BMC Health Serv Res

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BackgroundWarfarin is a drug with narrow therapeutic index used in the management of thromboembolic disorders. Several factors affect its plasma concentrations with a resultant risk of toxicity. We examined the database of patients on warfarin therapy in order to establish the factors that affect the stability of INR and correlated them to clinical outcomes in resource limited settings.MethodsWe analysed retrospective data of patients admitted to adult medical wards at Moi Teaching and Referral Hospital (MTRH) in 2015. Inclusion criteria were patients with thromboembolic and related disorders and on warfarin treatment. Derived data included demographics, indications for warfarin use, co-prescribed drugs, co-morbidities, INR measurements, duration of hospital stay and clinical outcomes. Descriptive statistics were used to summarize the data. Pearson’s correlation coefficient was used to assess relationships between duration of hospitalization and number of INR tests. Regression splines were used to capture INR trends during the follow up period. Data was analysed using R v. 3.3.1.ResultsA total of 310 patients had thromboembolic disorders, out of which 63 met the study criteria.The median age was 48 years, while the mean number of INR measurements was once every four days. Majority of patients did not achieve stable INR values, with only two having consecutive INR values within therapeutic goal. Patients who died had high INR levels. The median duration of hospital stay was 9 days (IQR: 7.0, 16.5). There was a significant correlation between length of stay in hospital and the number of times that INR were measured (Corr = 0.667, p < 0.001). The two most common indications for warfarin were DVT (64.4%) and atrial fibrillation (24.7%). All the patients had one or more comorbid conditions except for 11 with DVT alone, with cardiovascular diseases and infections being the most frequent, and on concomitant medications, majority of which are known to interact with warfarin.ConclusionsIt was difficult to achieve stable INR under the prevailing conditions despite the frequent tests.The potential factors that may have contributed to the fluctuations include drug-drug interactions, frequency of INR tests, comorbidities and the short duration of hospital stay.

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Section: Discussionmentioning

confidence: 99%

Characteristics of patients with thromboembolic disorders on warfarin therapy in resource limited settings

Kamuren

Kigen

Keter

et al. 2018

BMC Health Serv Res

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“…For example, medications such as beta-blockers and ACE inhibitors appear to be under-prescribed post-myocardial infarction in older patients with CKD. 34 Conversely, in other circumstances, CKD may increase the potential for medication side effects – for example from spironolactone 35 or warfarin 36 . Similarly, guidelines are conflicting regarding the optimal blood pressure targets and choice of blood pressure-lowering agents for older patients with CKD.…”

Section: Clinical and Public Health Implications Of Ckd In Older Adultsmentioning

confidence: 99%

Epidemiology and Public Health Concerns of CKD in Older Adults

Fung

Tamura

2016

Advances in Chronic Kidney Disease

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Chronic kidney disease is increasingly common in older adults. Estimating the glomerular filtration rate can be challenging in this population, with sarcopenia affecting the accuracy of various formulae. Competing risks of death influence the risk of progression to end stage kidney disease. In managing chronic kidney disease in this population, one must take into consideration other comorbidities including assessment of geriatric syndromes. More research is still needed to guide medical management in this heterogeneous population.

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“…12 However, in patients with ESRD, nonrenal clearance is diminished through downregulation of cytochrome P450 gene expression. 13 A consequent increase in the S/R enantiomer ratio 14 is the putative explanation for three important observations in ESRD patients: (1) reduced warfarin dose requirements; 15 (2) diminished time in therapeutic range regardless of international normalized ratio (INR) intensity; 16 and (3) increased time with excessive INR. 17 Nonetheless, decreased protein binding in ESRD 18 probably accounts for the 31% drop in warfarin concentration following hemodialysis, owing to partial filtration of unbound warfarin.…”

Section: Vitamin K Antagonistsmentioning

confidence: 99%

Direct Oral Anticoagulants in End-Stage Renal Disease

Klil-Drori

Tagalakis

2018

Semin Thromb Hemost

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Patients with end-stage renal disease (ESRD) were excluded from pivotal clinical trials with oral anticoagulants. While such patients are at an increased risk of venous and arterial thromboembolism, their risk of bleeding is also elevated. It is thus of little surprise that stroke prevention with vitamin K antagonists (VKAs) in ESRD patients with atrial fibrillation is controversial, with observational evidence ranging from beneficial to harmful. This uncertainty extends to the less studied use of VKAs for venous thromboembolism in ESRD. The direct oral anticoagulants (DOACs) apixaban and rivaroxaban have now permissive labeling in the United States for atrial fibrillation in patients with ESRD; this expanded labeling has not yet occurred either in Europe or for venous thromboembolism. This review summarizes the current evidence for the pharmacology of DOACs in ESRD as well as their utilization and safety in patients with ESRD and atrial fibrillation.

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Evaluation of Warfarin Dose Requirements in Patients with Chronic Kidney Disease and End‐Stage Renal Disease

Abstract: Our findings suggest that CKD and ESRD patients require ~20% lower warfarin doses to maintain a therapeutic INR and may require less time to achieve a therapeutic INR compared with patients with NKF.

Cited by 18 publications

References 27 publications

Characteristics of patients with thromboembolic disorders on warfarin therapy in resource limited settings

Characteristics of patients with thromboembolic disorders on warfarin therapy in resource limited settings

Epidemiology and Public Health Concerns of CKD in Older Adults

Direct Oral Anticoagulants in End-Stage Renal Disease

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