Stroke Prevention in Atrial Fibrillation in Patients With Chronic Kidney Disease
2016; Lippincott Williams & Wilkins; Volume: 133; Issue: 15 Linguagem: Inglês
10.1161/circulationaha.115.018549
ISSN1524-4539
Autores Tópico(s)Cardiac Imaging and Diagnostics
ResumoHomeCirculationVol. 133, No. 15Stroke Prevention in Atrial Fibrillation in Patients With Chronic Kidney Disease Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBStroke Prevention in Atrial Fibrillation in Patients With Chronic Kidney Disease Arman Qamar, MD and Deepak L. Bhatt, MD, MPH Arman QamarArman Qamar From Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA. and Deepak L. BhattDeepak L. Bhatt From Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA. Originally published12 Apr 2016https://doi.org/10.1161/CIRCULATIONAHA.115.018549Circulation. 2016;133:1512–1515Case Presentation: A 68-year-old woman with hypertension, diabetes mellitus, and congestive heart failure presented to the emergency department with palpitations. On physical examination, her heart rate was 130 bpm and irregularly irregular, her blood pressure was 120/70 mm Hg, and she weighed 60 kg. The ECG demonstrated atrial fibrillation (AF) with a rapid ventricular rate. Laboratory evaluation was remarkable for a serum creatinine of 1.3 mg/dL. Her symptoms resolved with heart rate control.BackgroundAF is the most common arrhythmia in patients with chronic kidney disease (CKD) and is associated with increased risk of stroke and thromboembolism. The risk of stroke increases as renal function declines. Conversely, patients with CKD, particularly those on hemodialysis, are at an increased risk of bleeding. Oral anticoagulation is the most effective form of thromboprophylaxis in patients with AF at increased risk of stroke. Concern for bleeding has resulted in the underuse of anticoagulation in these patients.Warfarin and novel oral anticoagulants (NOACs) have been shown to be effective in preventing stroke in the general population of patients with AF. However, most randomized trials of antithrombotic therapy have excluded patients with severe renal impairment (estimated creatinine clearance [eCrCl] 905 or 2.5 mg twice daily150 mg twice daily60 mg once daily20 mg once daily with evening meal51–905 or 2.5 mg twice daily150 mg twice daily60 mg once daily20 mg once daily with evening meal31–505 or 2.5 mg twice daily150 mg twice daily30 mg once daily15 mg once daily with evening meal15–305 or 2.5 mg twice daily75 mg twice daily30 mg once daily15 mg once daily with evening meal<15 not on dialysis5 or 2.5 mg twice dailyNot recommendedNot recommendedNot recommended 95 mL/min.Contemporary trials of apixaban, dabigatran, edoxaban, and rivaroxaban showed efficacy and safety that were comparable or superior to those of warfarin in patients with AF and moderate CKD (eCrCl, 30–49 mL·min−1·1.73 m−2; Figure).8–12 The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial demonstrated that apixaban compared with warfarin was associated with a lower risk of stroke, thromboembolism, major bleeding, and death in patients with moderate CKD.9 Similarly, in the RE-LY trial, dabigatran was superior to warfarin in patients with moderate CKD in preventing stroke and thromboembolism.10 In patients with moderate CKD in the Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48 (ENGAGE-AF TIMI 48) trial, edoxaban compared with warfarin showed similar efficacy in preventing stroke and a lower risk of bleeding and cardiovascular death.11 In agreement with previous studies, the 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) trial demonstrated a trend toward lower risk of stroke, thromboembolism, and fatal bleeding with rivaroxaban compared with warfarin in the subgroup with moderate CKD.12 Overall, these findings suggest that in patients with moderate CKD, NOACs have a favorable net clinical benefit.Download figureDownload PowerPointFigure. Efficacy and safety of novel oral anticoagulants (NOACs) vs warfarin in the subgroup of patients with moderate chronic kidney disease (CKD) from randomized, clinical trials in atrial fibrillation. Comparison of hazard ratios and 95% confidence intervals (CIs) for primary efficacy and safety outcomes for 150 and 110 mg dabigatran twice daily, 15 mg rivaroxaban once daily, 5 mg apixaban twice daily, and 30 mg edoxaban once daily. CKD was defined as estimated creatinine clearance (eCrCl) of 30 to 49 mL·min−1·1.73 m−2 or as 25 to 49 mL/min for apixaban. *Apixaban 2.5 mg twice daily if patient had any 2 of the following: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. Reproduced from Qamar and Bhatt8 with permission from the publisher. Copyright © 2015 Nature Publishing Group.None of the NOACs have been well studied in patients with AF who are on dialysis or have eCrCl <30 mL·min−1·1.73 m−2. Dabigatran, edoxaban, and rivaroxaban are not approved for use in patients on dialysis. Apixaban is approved on the basis of pharmacokinetic data. In a retrospective analysis of 29 977 patients with AF on hemodialysis in the United States, Chan et al13 found dabigatran or rivaroxaban to be associated with an increased risk of hospitalization or death resulting from bleeding compared with warfarin.Summary and Management of Presented CaseThe efficacy and safety of NOACs are superior or comparable to those of warfarin in patients with AF and moderate CKD. If clinicians choose to use NOACs in patients with moderate CKD, frequent monitoring of renal function and dose adjustments are crucial. Large-scale, randomized, controlled trials would be desirable to examine the efficacy and safety of NOACs and warfarin in patients with severe renal impairment (eCrCl <30 mL·min−1·1.73 m−2) and those on dialysis. Until then, in the absence of major contraindications, warfarin with careful international normalized ratio monitoring should generally be prescribed in patients with AF and severe renal impairment, including those on dialysis, although apixaban is an approved option.Our patient represents a patient with AF with moderate CKD. Despite her modest creatinine elevation, her eCrCl calculates to 39.2 mL/min, underscoring the importance of not basing decisions on creatinine alone. Her annual stroke risk is 6.7% based on a CHA2DS2-VASc score of 5. We recommended anticoagulation with apixaban 5 mg twice daily for the prevention of stroke and systemic embolism, with a plan for close monitoring of her renal function. We chose apixaban because of the lower risk of bleeding compared with warfarin.9 Thromboprophylaxis with adjusted dosing of dabigatran, edoxaban, or rivaroxaban or with warfarin would also have been reasonable.DisclosuresDr Bhatt discloses the following relationships: Advisory Board: Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; Board of Directors: Boston VA Research Institute and Society of Cardiovascular Patient Care; chair: American Heart Association Get With The Guidelines Steering Committee; Data Monitoring Committee: Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, and Population Health Research Institute; honoraria: American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org), Belvoir Publications (editor in chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (editor in chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor; associate editor), Population Health Research Institute (clinical trial steering committee), Slack Publications (chief medical editor, Cardiology Today's Intervention), and WebMD (CME steering committees); other: Clinical Cardiology (deputy editor); research funding: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Forest Laboratories, Ischemix, Medtronic, Pfizer, Roche, Sanofi Aventis, and The Medicines Company; site coinvestigator: Biotronik and St. Jude Medical; trustee: American College of Cardiology; and unfunded research: FlowCo, PLx Pharma, and Takeda. Dr Qamar reports no conflicts.FootnotesCorrespondence to Deepak L. Bhatt, MD, MPH, FAHA, Brigham and Women's Hospital Heart & Vascular Center, 75 Francis St, Boston, MA 02115. E-mail [email protected]References1. Bonde AN, Lip GY, Kamper AL, Hansen PR, Lamberts M, Hommel K, Hansen ML, Gislason GH, Torp-Pedersen C, Olesen JB. Net clinical benefit of antithrombotic therapy in patients with atrial fibrillation and chronic kidney disease: a nationwide observational cohort study.J Am Coll Cardiol. 2014; 64:2471–2482. doi: 10.1016/j.jacc.2014.09.051.CrossrefMedlineGoogle Scholar2. Olesen JB, Lip GY, Kamper AL, Hommel K, Køber L, Lane DA, Lindhardsen J, Gislason GH, Torp-Pedersen C. Stroke and bleeding in atrial fibrillation with chronic kidney disease.N Engl J Med. 2012; 367:625–635. doi: 10.1056/NEJMoa1105594.CrossrefMedlineGoogle Scholar3. Carrero JJ, Evans M, Szummer K, Spaak J, Lindhagen L, Edfors R, Stenvinkel P, Jacobson SH, Jernberg T. 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