Patient Presentation Overview: A 76-year-old male presents to establish cardiac care from a neighboring state.
Positive Past Medical History: Diabetes mellitus type II, hypertension, hyperlipidemia, presumed transient ischemic attack, chronic kidney disease (CKD), and atrial fibrillation.
Medications (Name, Dose, and Frequency): Metoprolol succinate 100 mg daily, atorvastatin 40 mg daily, ASA 81 mg daily, and lisinopril 10 mg daily
Medication Allergies: None
Pertinent Social, Family History: He lives alone and is able to complete all of his activities of daily living without problems. He still drives short distances and recently moved to live with his adult children.
Review of Systems: He denies any falls in the past and does not use an assistive device for ambulation. He denies chest pain and dyspnea on exertion. He denies lower extremity edema, orthopnea, and paroxysmal nocturnal dyspnea. He denies any palpitations, syncope, or presyncope.
Vitals
Blood Pressure: 135/80 mm Hg
Heart Rate: 90 bpm
Weight: 75 kg
Focused Physical Exam
General: Appears well, not distressed, well nourished
Neck: Supple, no visible jugular venous distension
Cardiovascular: Irregular S1 without murmur or gallop
Respiratory: Clear to auscultation bilaterally
Abdomen: Soft and non-tender to palpitation
Neurological: No focal deficient, can perform sit to stand without assistance
Extremities: Warm and well perfused, no edema or venous stasis changes
Pertinent Laboratory Data
Hemoglobin: 13 gm/dL
Creatinine: 2.0 (estimated glomerular filtration rate [eGFR] 32 ml/min/m2 by CKD-EPI equation)
Pertinent Cardiac Studies
Electrocardiogram (ECG): An ECG confirms atrial fibrillation with a ventricular rate of 90.
Transthoracic Echocardiography: Transthoracic echocardiogram shows a normal left ventricular ejection fraction and no regional dysfunction. There is left ventricular hypertrophy and marked left atrial enlargement. Filling pressures appear normal.
Additional Pertinent Comments: The patient and his family are unsure if he has ever been prescribed anticoagulants in the past and would prefer a medication that did not require frequent laboratory assessment.
The correct answer is: B. Dabigatran 75 mg twice daily.
For this patient with CKD stage 3 (based on eGFR between 30-35 ml/min/m2), it would appear from the literature that any of the newer anticoagulants would be acceptable alternatives as long as appropriate renal dose adjustment has been performed. Apixaban has been demonstrated to be associated with reduced bleeding risk relative to warfarin among patients with CKD stage 3. Rivaroxaban has been shown to have a lower risk of fatal bleeding. Edoxaban has also been shown to be associated with significantly lower bleeding risk among patients with eCrCl<90 ml/kg/min. and lower rates of intracranial hemorrhage relative to warfarin, but higher rates of gastrointestinal bleeding.
Among the answer options provided, the critical aspect pertaining to the choice of the anticoagulant is appropriate renal dose adjustment for CKD stage 3. It should be noted by clinicians that the U.S. Food and Drug Administration (FDA) approved label for the newer anticoagulants is based on levels of estimated creatinine clearance. In clinical practice, clinicians commonly use estimates of glomerular filtration rate which, although similar to estimated creatinine clearance, are not necessarily interchangeable values.
The dose of rivaroxaban in Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) was 15 mg daily for stage 3 CKD. The dose of apixaban was reduced to 2.5 mg twice daily in ARISTOTLE when two of the following criteria were met: age ≥80 years, weight ≤60 kg and creatinine ≥1.5 mg/dl. Thus, age and body weight are important determinants of appropriate dosing for apixaban; for the patient in this case, a dose of apixaban 5 mg twice daily would have been used in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial based on age and weight. Based on the results of the Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) trial, edoxaban is recommended to be used at a lower dose of 30 mg daily among patients with CKD stage 3.
Dabigatran 75 mg PO twice daily has been approved by the FDA only for patients with CKD stage 4; this is a controversial label that has not received approval from other regulatory bodies worldwide,1 mainly because of a lack of randomized evidence to support this dose. The FDA-approved dose of dabigatran for stroke prevention among patients with CKD stage 3 is 150 mg PO twice daily.
There have been specific concerns raised about the safety of use of novel oral anticoagulants (NOACs) in geriatric patients with CKD.2 A meta-analysis by Sardar et al. evaluated data among elderly (>75 years) patients from 10 randomized trials for a variety of clinical indications. They found no significant increase in major bleeding in this population with use of NOACs versus conventional therapy. Additionally, they reported a lower risk of stroke and systemic embolism with NOAC versus conventional therapy among patients with atrial fibrillation.3
References
- Hart RG, Eikelboom JW, Ingram AJ, Herzog CA. Anticoagulants in atrial fibrillation patients with chronic kidney disease. Nat Rev Nephrol 2012;8:569-78.
- Harper P, Young L, Merriman E. Bleeding risk with dabigatran in the frail elderly. N Engl J Med 2012;366:864-6.
- Sardar P, Chatterjee S, Chaudhari S, Lip GY. New oral anticoagulants in elderly adults: evidence from a meta-analysis of randomized trials. J Am Geriatr Soc 2014;62:857-64.
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