Key Points
-
Atrial fibrillation (AF) and chronic kidney disease (CKD) share common risk factors, including older age, hypertension and diabetes mellitus.
-
CKD increases the risk of incident AF, whereas AF increases the risk of development and progression of CKD.
-
AF and CKD are associated with an increased risk of thromboembolic events; patients with severe CKD also exhibit a paradoxical increase in bleeding risk.
-
In trials that compared non-vitamin K antagonist oral anticoagulants (NOACs) with warfarin, the relative efficacy and safety of NOACs were consistent in patients with and without mild or moderate CKD.
-
Patients with end-stage renal disease (ESRD) were excluded from NOAC trials; these patients are at high risk of thromboembolism and bleeding, but no high-quality evidence exists to guide their management.
-
In patients with ESRD, vitamin K antagonists might increase the risk of bleeding and thrombotic events; however, good anticoagulation control might reduce the risk of ischaemic stroke without increasing bleeding risk.
Abstract
Atrial fibrillation (AF) and chronic kidney disease (CKD) are increasingly prevalent in the general population and share common risk factors such as older age, hypertension and diabetes mellitus. The presence of CKD increases the risk of incident AF, and, likewise, AF increases the risk of CKD development and/or progression. Both conditions are associated with substantial thromboembolic risk, but patients with advanced CKD also exhibit a paradoxical increase in bleeding risk. In the landmark randomized clinical trials that compared non-vitamin K antagonist oral anticoagulants (NOACs) with warfarin for thromboprophylaxis in patients with AF, the efficacy and safety of NOACs in patients with mild-to-moderate CKD were similar to those in patients without CKD. Dose adjustment of NOACs as per the prescribing label is required in this population. Owing to limited trial data, evidence-based recommendations for the management of patients with AF and severe CKD or end-stage renal disease on dialysis are lacking. Observational cohort studies have reported conflicting results, and the management of these particularly vulnerable patients remains challenging and requires careful assessment of stroke and bleeding risk and, where appropriate, use of warfarin with good-quality anticoagulation control.
Similar content being viewed by others
References
Hill, N. R. et al. Global Prevalence of Chronic Kidney Disease - A Systematic Review and Meta-Analysis. PloS One 11, e0158765 (2016).
Jha, V. et al. Chronic kidney disease: global dimension and perspectives. Lancet 382, 260–272 (2013).
Benjamin, E. J. et al. Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation 135, e146–e603 (2017).
Lip, G. Y. et al. Atrial fibrillation. Nat. Rev. Dis. Primers 2, 16016 (2016).
Baber, U. et al. Association of chronic kidney disease with atrial fibrillation among adults in the United States: REasons for Geographic and Racial Differences in Stroke (REGARDS) Study. Circul. Arrhythmia Electrophysiol. 4, 26–32 (2011).
Liao, J. N. et al. Incidence and risk factors for new-onset atrial fibrillation among patients with end-stage renal disease undergoing renal replacement therapy. Kidney Int. 87, 1209–1215 (2015).
Soliman, E. Z. et al. Chronic kidney disease and prevalent atrial fibrillation: the Chronic Renal Insufficiency Cohort (CRIC). Am. Heart J. 159, 1102–1107 (2010).
Alonso, A. et al. Chronic kidney disease is associated with the incidence of atrial fibrillation: the Atherosclerosis Risk in Communities (ARIC) study. Circulation 123, 2946–2953 (2011).
Ohyama, Y., Imai, M. & Kurabayashi, M. Estimated glomerular filtration rate and proteinuria are separately and independently associated with the prevalence of atrial fibrillation in general population. PloS One 8, e79717 (2013).
Suzuki, S. et al. Estimated glomerular filtration rate and proteinuria are associated with persistent form of atrial fibrillation: analysis in Japanese patients. J. Cardiol. 61, 53–57 (2013).
McManus, D. D., Corteville, D. C., Shlipak, M. G., Whooley, M. A. & Ix, J. H. Relation of kidney function and albuminuria with atrial fibrillation (from the Heart and Soul Study). Am. J. Cardiol. 104, 1551–1555 (2009).
Nelson, S. E., Shroff, G. R., Li, S. & Herzog, C. A. Impact of chronic kidney disease on risk of incident atrial fibrillation and subsequent survival in medicare patients. J. Am. Heart Assoc. 1, e002097 (2012).
Bansal, N. et al. Incident atrial fibrillation and risk of end-stage renal disease in adults with chronic kidney disease. Circulation 127, 569–574 (2013).
Guo, Y. et al. Sequential changes in renal function and the risk of stroke and death in patients with atrial fibrillation. Int. J. Cardiol. 168, 4678–4684 (2013).
Watanabe, H. et al. Close bidirectional relationship between chronic kidney disease and atrial fibrillation: the Niigata preventive medicine study. Am. Heart J. 158, 629–636 (2009).
Zimmerman, D. et al. Systematic review and meta-analysis of incidence, prevalence and outcomes of atrial fibrillation in patients on dialysis. Nephrol., Dialysis Transplant. 27, 3816–3822 (2012).
Kirchhof, P. et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur. Heart J. 37, 2893–2962 (2016).
January, C. T. et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J. Am. College Cardiol. 64, e1–76 (2014).
Bos, M. J., Koudstaal, P. J., Hofman, A. & Breteler, M. M. Decreased glomerular filtration rate is a risk factor for hemorrhagic but not for ischemic stroke: the Rotterdam Study. Stroke; J. Cerebral Circul. 38, 3127–3132 (2007).
Iseki, K., Kinjo, K., Kimura, Y., Osawa, A. & Fukiyama, K. Evidence for high risk of cerebral hemorrhage in chronic dialysis patients. Kidney Int. 44, 1086–1090 (1993).
Ovbiagele, B. et al. Association of chronic kidney disease with cerebral microbleeds in patients with primary intracerebral hemorrhage. Stroke; J. Cerebral Circul. 44, 2409–2413 (2013).
Sood, P. et al. Chronic kidney disease and end-stage renal disease predict higher risk of mortality in patients with primary upper gastrointestinal bleeding. Am. J. Nephrol. 35, 216–224 (2012).
Kuo, C. C., Kuo, H. W., Lee, I. M., Lee, C. T. & Yang, C. Y. The risk of upper gastrointestinal bleeding in patients treated with hemodialysis: a population-based cohort study. BMC Nephrol. 14, 15 (2013).
Luo, J. C. et al. Nonpeptic ulcer, nonvariceal gastrointestinal bleeding in hemodialysis patients. Am. J. Med. 126, 264.e25–264.e32 (2013).
Connolly, S. J. et al. Dabigatran versus warfarin in patients with atrial fibrillation. N. Engl. J. Med. 361, 1139–1151 (2009).
Patel, M. R. et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N. Engl. J. Med. 365, 883–891 (2011).
Granger, C. B. et al. Apixaban versus warfarin in patients with atrial fibrillation. N. Engl. J. Med. 365, 981–992 (2011).
Giugliano, R. P. et al. Edoxaban versus warfarin in patients with atrial fibrillation. N. Engl. J. Med. 369, 2093–2104 (2013).
Stroke Prevention in Atrial Fibrillation Investigators. Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial. Lancet 348, 633–638 (1996).
Hart, R. G., Pearce, L. A., Asinger, R. W. & Herzog, C. A. Warfarin in atrial fibrillation patients with moderate chronic kidney disease. Clin. J. Am. Soc. Nephrol. 6, 2599–2604 (2011).
Vassalotti, J. A., Li, S., McCullough, P. A. & Bakris, G. L. Kidney early evaluation program: a community-based screening approach to address disparities in chronic kidney disease. Semin. Nephrol. 30, 66–73 (2010).
Minutolo, R. et al. Detection and awareness of moderate to advanced CKD by primary care practitioners: a cross-sectional study from Italy. Am. J. Kidney Dis. 52, 444–453 (2008).
Plantinga, L. C. et al. Patient awareness of chronic kidney disease: trends and predictors. Arch. Internal Med. 168, 2268–2275 (2008).
Chugh, S. S. et al. Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation 129, 837–847 (2014).
Freedman, B., Potpara, T. S. & Lip, G. Y. Stroke prevention in atrial fibrillation. Lancet 388, 806–817 (2016).
Lau, Y. C., Proietti, M., Guiducci, E., Blann, A. D. & Lip, G. Y. H. Atrial fibrillation and thromboembolism in patients with chronic kidney disease. J. Am. College Cardiol. 68, 1452–1464 (2016).
Hobbs, F. D. et al. A randomised controlled trial and cost-effectiveness study of systematic screening (targeted and total population screening) versus routine practice for the detection of atrial fibrillation in people aged 65 and over. The SAFE study. Health Technol. Assess. 9, iii–iv, ix–x, 1–74 (2005).
Goldstein, B. A. et al. Trends in the incidence of atrial fibrillation in older patients initiating dialysis in the United States. Circulation 126, 2293–2301 (2012).
Buiten, M. S. et al. The dialysis procedure as a trigger for atrial fibrillation: new insights in the development of atrial fibrillation in dialysis patients. Heart 100, 685–690 (2014).
Lentine, K. L. et al. Incidence, predictors, and associated outcomes of atrial fibrillation after kidney transplantation. Clin. J. Am. Soc. Nephrol. 1, 288–296 (2006).
Schnabel, R. B. et al. 50 year trends in atrial fibrillation prevalence, incidence, risk factors, and mortality in the Framingham Heart Study: a cohort study. Lancet 386, 154–162 (2015).
Bansal, N., Hsu, C. Y. & Go, A. S. Intersection of cardiovascular disease and kidney disease: atrial fibrillation. Curr. Opin. Nephrol. Hypertens. 23, 275–282 (2014).
Foley, R. N., Curtis, B. M., Randell, E. W. & Parfrey, P. S. Left ventricular hypertrophy in new hemodialysis patients without symptomatic cardiac disease. Clin. J. Am. Soc. Nephrol. 5, 805–813 (2010).
Levin, A. & Foley, R. N. Cardiovascular disease in chronic renal insufficiency. Am. J. Kidney Dis. 36, S24–S30 (2000).
Bansal, N. et al. A longitudinal study of left ventricular function and structure from CKD to ESRD: the CRIC study. Clin. J. Am. Soc. Nephrol. 8, 355–362 (2013).
Eckardt, K. U. et al. Left ventricular geometry predicts cardiovascular outcomes associated with anemia correction in CKD. J. Am. Soc. Nephrol. 20, 2651–2660 (2009).
Foley, R. N. et al. Serial change in echocardiographic parameters and cardiac failure in end-stage renal disease. J. Am. Soc. Nephrol. 11, 912–916 (2000).
Yamamoto, K. T. et al. Dietary phosphorus is associated with greater left ventricular mass. Kidney Int. 83, 707–714 (2013).
Gutierrez, O. M. et al. Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease. Circulation 119, 2545–2552 (2009).
Melamed, M. L. & Thadhani, R. I. Vitamin D therapy in chronic kidney disease and end stage renal disease. Clin. J. Am. Soc. Nephrol. 7, 358–365 (2012).
Ketteler, M., Schlieper, G. & Floege, J. Calcification and cardiovascular health: new insights into an old phenomenon. Hypertension 47, 1027–1034 (2006).
Ochodnicky, P., Henning, R. H., van Dokkum, R. P. & de Zeeuw, D. Microalbuminuria and endothelial dysfunction: emerging targets for primary prevention of end-organ damage. J. Cardiovasc. Pharmacol. 47 (Suppl. 2), S151–S162; discussion S172-156 (2006).
Krane, V. & Wanner, C. Statins, inflammation and kidney disease. Nat. Rev. Nephrol. 7, 385–397 (2011).
Gupta, J. et al. Association between albuminuria, kidney function, and inflammatory biomarker profile in CKD in CRIC. Clin. J. Am. Soc. Nephrol.: CJASN 7, 1938–1946 (2012).
Upadhyay, A. et al. Inflammation, kidney function and albuminuria in the Framingham Offspring cohort. Nephrol. Dialysis Transplant. 26, 920–926 (2011).
Khatib, R., Joseph, P., Briel, M., Yusuf, S. & Healey, J. Blockade of the renin-angiotensin-aldosterone system (RAAS) for primary prevention of non-valvular atrial fibrillation: a systematic review and meta analysis of randomized controlled trials. Int. J. Cardiol. 165, 17–24 (2013).
Schlaich, M. P. et al. Sympathetic activation in chronic renal failure. J. Am. Soc. Nephrol. 20, 933–939 (2009).
Pecoits-Filho, R. et al. Associations between circulating inflammatory markers and residual renal function in CRF patients. Am. J. Kidney Dis. 41, 1212–1218 (2003).
Bansal, N. et al. Atrial Fibrillation and Risk of ESRD in Adults with CKD. Clin. J. Am. Soc. Nephrol. 11, 1189–1196 (2016).
Goette, A. et al. EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication. Europace 18, 1455–1490 (2016).
Chen, S. C. et al. Echocardiographic parameters are independently associated with rate of renal function decline and progression to dialysis in patients with chronic kidney disease. Clin. J. Am. Soc. Nephrol. 6, 2750–2758 (2011).
Olesen, J. B. et al. Stroke and bleeding in atrial fibrillation with chronic kidney disease. N. Engl. J. Med. 367, 625–635 (2012).
Banerjee, A. et al. A prospective study of estimated glomerular filtration rate and outcomes in patients with atrial fibrillation: the Loire Valley Atrial Fibrillation Project. Chest 145, 1370–1382 (2014).
Friberg, L., Rosenqvist, M. & Lip, G. Y. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Eur. Heart J. 33, 1500–1510 (2012).
Go, A. S. et al. Impact of proteinuria and glomerular filtration rate on risk of thromboembolism in atrial fibrillation: the anticoagulation and risk factors in atrial fibrillation (ATRIA) study. Circulation 119, 1363–1369 (2009).
Wetmore, J. B. et al. Atrial fibrillation and risk of stroke in dialysis patients. Ann. Epidemiol. 23, 112–118 (2013).
Wetmore, J. B. et al. Stroke and the “stroke belt” in dialysis: contribution of patient characteristics to ischemic stroke rate and its geographic variation. J. Am. Soc. Nephrol. 24, 2053–2061 (2013).
Wizemann, V. et al. Atrial fibrillation in hemodialysis patients: clinical features and associations with anticoagulant therapy. Kidney Int. 77, 1098–1106 (2010).
Lenihan, C. R., Montez-Rath, M. E., Scandling, J. D., Turakhia, M. P. & Winkelmayer, W. C. Outcomes after kidney transplantation of patients previously diagnosed with atrial fibrillation. Am. J. Transplant 13, 1566–1575 (2013).
Huang, K. W. et al. Different peptic ulcer bleeding risk in chronic kidney disease and end-stage renal disease patients receiving different dialysis. Dig. Dis. Sci. 59, 807–813 (2014).
Jalal, D. I., Chonchol, M. & Targher, G. Disorders of hemostasis associated with chronic kidney disease. Semin. Thromb. Hemost 36, 34–40 (2010).
Molino, D., De Lucia, D. & Gaspare De Santo, N. Coagulation disorders in uremia. Semin. Nephrol. 26, 46–51 (2006).
Lutz, J., Menke, J., Sollinger, D., Schinzel, H. & Thurmel, K. Haemostasis in chronic kidney disease. Nephrol, Dialysis Transplant. 29, 29–40 (2014).
Calenda, B. W., Fuster, V., Halperin, J. L. & Granger, C. B. Stroke risk assessment in atrial fibrillation: risk factors and markers of atrial myopathy. Nature reviews. Cardiology 13, 549–559 (2016).
Watson, T., Shantsila, E. & Lip, G. Y. Mechanisms of thrombogenesis in atrial fibrillation: Virchow's triad revisited. Lancet 373, 155–166 (2009).
Keller, C., Katz, R., Cushman, M., Fried, L. F. & Shlipak, M. Association of kidney function with inflammatory and procoagulant markers in a diverse cohort: a cross-sectional analysis from the Multi-Ethnic Study of Atherosclerosis (MESA). BMC Nephrol. 9, 9 (2008).
Healey, J. S., Morillo, C. A. & Connolly, S. J. Role of the renin-angiotensin-aldosterone system in atrial fibrillation and cardiac remodeling. Curr. Opin. Cardiol. 20, 31–37 (2005).
Chue, C. D., Townend, J. N., Steeds, R. P. & Ferro, C. J. Arterial stiffness in chronic kidney disease: causes and consequences. Heart 96, 817–823 (2010).
Wang, M. C., Tsai, W. C., Chen, J. Y. & Huang, J. J. Stepwise increase in arterial stiffness corresponding with the stages of chronic kidney disease. Am. J. Kidney Dis. 45, 494–501 (2005).
Carrero, J. J. et al. Prolactin levels, endothelial dysfunction, and the risk of cardiovascular events and mortality in patients with CKD. Clin. J. Am. Soc. Nephrol. 7, 207–215 (2012).
Ghosh, A. K. & Vaughan, D. E. PAI-1 in tissue fibrosis. J. Cell. Physiol. 227, 493–507 (2012).
Sobel, B. E., Taatjes, D. J. & Schneider, D. J. Intramural plasminogen activator inhibitor type-1 and coronary atherosclerosis. Arterioscler Thromb. Vasc. Biol. 23, 1979–1989 (2003).
Mercier, E. et al. Tissue factor coagulation pathway and blood cells activation state in renal insufficiency. Hematol. J. 2, 18–25 (2001).
Lip, G., Freedman, B., De Caterina, R. & Potpara, T. S. Stroke prevention in atrial fibrillation: Past, present and future. Comparing the guidelines and practical decision-making. Thromb. Haemostasis 117, 1230–1239 (2017).
Dahal, K., Kunwar, S., Rijal, J., Schulman, P. & Lee, J. Stroke, major bleeding, and mortality outcomes in warfarin users with atrial fibrillation and chronic kidney disease: a meta-analysis of observational studies. Chest 149, 951–959 (2016).
Tan, J., Liu, S., Segal, J. B., Alexander, G. C. & McAdams-DeMarco, M. Warfarin use and stroke, bleeding and mortality risk in patients with end stage renal disease and atrial fibrillation: a systematic review and meta-analysis. BMC Nephrol. 17, 157 (2016).
Chan, K. E., Lazarus, J. M., Thadhani, R. & Hakim, R. M. Warfarin use associates with increased risk for stroke in hemodialysis patients with atrial fibrillation. J. Am. Soc. Nephrol. 20, 2223–2233 (2009).
Winkelmayer, W. C., Liu, J., Setoguchi, S. & Choudhry, N. K. Effectiveness and safety of warfarin initiation in older hemodialysis patients with incident atrial fibrillation. Clin. J. Am. Soc. Nephrol. 6, 2662–2668 (2011).
Keskar, V. et al. The association of anticoagulation, ischemic stroke, and hemorrhage in elderly adults with chronic kidney disease and atrial fibrillation. Kidney Int. 91, 928–936 (2017).
Shen, J. I. et al. Outcomes after warfarin initiation in a cohort of hemodialysis patients with newly diagnosed atrial fibrillation. Am. J. Kidney Dis. 66, 677–688 (2015).
Knoll, F. et al. Coumarins and survival in incident dialysis patients. Nephrol. Dialysis Transplant. 27, 332–337 (2012).
Chen, J. J. et al. Anti-platelet or anti-coagulant agent for the prevention of ischemic stroke in patients with end-stage renal disease and atrial fibrillation — a nation-wide database analyses. Int. J. Cardiol. 177, 1008–1011 (2014).
Chan, P. H. et al. Ischaemic stroke in patients with atrial fibrillation with chronic kidney disease undergoing peritoneal dialysis. Europace 18, 665–671 (2016).
Bonde, A. N. et al. Net clinical benefit of antithrombotic therapy in patients with atrial fibrillation and chronic kidney disease: a nationwide observational cohort study. J. Am. College Cardiol. 64, 2471–2482 (2014).
Genovesi, S. et al. Warfarin use, mortality, bleeding and stroke in haemodialysis patients with atrial fibrillation. Nephrol, Dialysis Transplant. 30, 491–498 (2015).
Findlay, M. D. et al. Risk factors of ischemic stroke and subsequent outcome in patients receiving hemodialysis. Stroke 46, 2477–2481 (2015).
Abbott, K. C., Trespalacios, F. C., Taylor, A. J. & Agodoa, L. Y. Atrial fibrillation in chronic dialysis patients in the United States: risk factors for hospitalization and mortality. BMC Nephrol. 4, 1 (2003).
Friberg, L., Benson, L. & Lip, G. Y. Balancing stroke and bleeding risks in patients with atrial fibrillation and renal failure: the Swedish Atrial Fibrillation Cohort study. Eur. Heart J. 36, 297–306 (2015).
Sjogren, V. et al. Safety and efficacy of well managed warfarin. A Rep. From Swedish Qual. Register Auricula. Thromb. Haemost. 113, 1370–1377 (2015).
Proietti, M., Lane, D. A. & Lip, G. Y. Chronic kidney disease, time in therapeutic range and adverse clinical outcomes in anticoagulated patients with non-valvular atrial fibrillation: observations from the SPORTIF trials. EBioMedicine 8, 309–316 (2016).
Bonde, A. N. et al. Effect of reduced renal function on time in therapeutic range among anticoagulated atrial fibrillation patients. J. Am. College Cardiol. 69, 752–753 (2017).
Yang, F. et al. Warfarin utilisation and anticoagulation control in patients with atrial fibrillation and chronic kidney disease. Heart 103, 818–826 (2017).
Garcia, D. A., Lopes, R. D. & Hylek, E. M. New-onset atrial fibrillation and warfarin initiation: high risk periods and implications for new antithrombotic drugs. Thromb. Haemostasis 104, 1099–1105 (2010).
Jun, M. et al. The association between kidney function and major bleeding in older adults with atrial fibrillation starting warfarin treatment: population based observational study. BMJ 350, h246 (2015).
Andrews, J. et al. Warfarin use is associated with progressive coronary arterial calcification: insights from serial intravascular ultrasound. JACC Cardiovasc. Imag. https://doi.org/10.1016/j.jcmg.2017.04.010 (2017).
Koos, R. et al. Relation of circulating Matrix Gla-Protein and anticoagulation status in patients with aortic valve calcification. Thromb. Haemostasis 101, 706–713 (2009).
Brodsky, S. V. et al. Warfarin-related nephropathy occurs in patients with and without chronic kidney disease and is associated with an increased mortality rate. Kidney Int. 80, 181–189 (2011).
Yang, Y., Liu, T., Zhao, J. & Li, G. Warfarin-related nephropathy: prevalence, risk factors and prognosis. Int. J. Cardiol. 176, 1297–1298 (2014).
Galloway, P. A. et al. Vitamin K antagonists predispose to calciphylaxis in patients with end-stage renal disease. Nephron 129, 197–201 (2015).
Mazurek, M. et al. Regional Differences in Antithrombotic Treatment for Atrial Fibrillation: Insights from the GLORIA-AF Phase II Registry. Thromb. Haemostasis 117, 2376–2388 (2017).
Ruff, C. T. et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 383, 955–962 (2014).
Raparelli, V. et al. Adherence to oral anticoagulant therapy in patients with atrial fibrillation. Focus on non-vitamin K antagonist oral anticoagulants. Thromb. Haemostasis 117, 209–218 (2017).
Hijazi, Z. et al. Efficacy and safety of dabigatran compared with warfarin in relation to baseline renal function in patients with atrial fibrillation: a RE-LY (Randomized Evaluation of Long-term Anticoagulation Therapy) trial analysis. Circulation 129, 961–970 (2014).
Fox, K. A. et al. Prevention of stroke and systemic embolism with rivaroxaban compared with warfarin in patients with non-valvular atrial fibrillation and moderate renal impairment. Eur. Heart J. 32, 2387–2394 (2011).
Hohnloser, S. H. et al. Efficacy of apixaban when compared with warfarin in relation to renal function in patients with atrial fibrillation: insights from the ARISTOTLE trial. Eur. Heart J. 33, 2821–2830 (2012).
Bohula, E. A. et al. Impact of renal function on outcomes with edoxaban in the ENGAGE AF-TIMI 48 Trial. Circulation 134, 24–36 (2016).
Nielsen, P. B., Lane, D. A., Rasmussen, L. H., Lip, G. Y. & Larsen, T. B. Renal function and non-vitamin K oral anticoagulants in comparison with warfarin on safety and efficacy outcomes in atrial fibrillation patients: a systemic review and meta-regression analysis. Clin. Res. Cardiol. 104, 418–429 (2015).
Hijazi, Z. et al. Efficacy and Safety of Apixaban Compared With Warfarin in Patients With Atrial Fibrillation in Relation to Renal Function Over Time: Insights From the ARISTOTLE Randomized Clinical Trial. JAMA Cardiol. 1, 451–460 (2016).
Fordyce, C. B. et al. On-treatment outcomes in patients with worsening renal function with rivaroxaban compared with warfarin: insights from ROCKET AF. Circulation 134, 37–47 (2016).
Bohm, M. et al. Changes in renal function in patients with atrial fibrillation: an analysis from the RE-LY trial. J. Am. College Cardiol. 65, 2481–2493 (2015).
Chan, Y. H. et al. Acute Kidney Injury in Asians With Atrial Fibrillation Treated With Dabigatran or Warfarin. J. Am. College Cardiol. 68, 2272–2283 (2016).
Heidbuchel, H. et al. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace. 17, 1467–1507 (2015).
Food & Drug Administration, U. S. FDA approved drug products: label information for PRADAXA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022512s009lbl.pdf Vol. 2018.
Food & Drug Administration, U. S. FDA approved drug products: label information for ELIQUIS. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/202155s012lbl.pdf Vol. 2018.
Wang, X. et al. Pharmacokinetics, pharmacodynamics, and safety of apixaban in subjects with end-stage renal disease on hemodialysis. J. Clin. Pharmacol. 56, 628–636 (2016).
Stangier, J., Rathgen, K., Stahle, H. & Mazur, D. Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate: an open-label, parallel-group, single-centre study. Clin. Pharmacokinet. 49, 259–268 (2010).
Mavrakanas, T. A., Samer, C. F., Nessim, S. J., Frisch, G. & Lipman, M. L. Apixaban Pharmacokinetics at Steady State in Hemodialysis Patients. J. Am. Soc. Nephrol. 28, 2241–2248 (2017).
De Vriese, A. S. et al. Dose-finding study of rivaroxaban in hemodialysis patients. Am. J. Kidney Dis. 66, 91–98 (2015).
Koretsune, Y. et al. Short-term safety and plasma concentrations of edoxaban in Japanese patients with non-valvular atrial fibrillation and severe renal impairment. Circ. J. 79, 1486–1495 (2015).
Food & Drug Administration, U. S. FDA approved drug products: label information for SAVAYSA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/206316s012lbl.pdf Vol. 2018.
Chan, K. E., Edelman, E. R., Wenger, J. B., Thadhani, R. I. & Maddux, F. W. Dabigatran and rivaroxaban use in atrial fibrillation patients on hemodialysis. Circulation 131, 972–979 (2015).
Yao, X., Shah, N. D., Sangaralingham, L. R., Gersh, B. J. & Noseworthy, P. A. Non-vitamin K antagonist oral anticoagulant dosing in patients with atrial fibrillation and renal dysfunction. J. Am. College Cardiol. 69, 2779–2790 (2017).
Olesen, J. B., Torp-Pedersen, C., Hansen, M. L. & Lip, G. Y. The value of the CHA2DS2-VASc score for refining stroke risk stratification in patients with atrial fibrillation with a CHADS2 score 0-1: a nationwide cohort study. Thromb. Haemostasis 107, 1172–1179 (2012).
Piccini, J. P. et al. Renal dysfunction as a predictor of stroke and systemic embolism in patients with nonvalvular atrial fibrillation: validation of the R(2)CHADS(2) index in the ROCKET AF (Rivaroxaban Once-daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) and ATRIA (AnTicoagulation and Risk factors In Atrial fibrillation) study cohorts. Circulation 127, 224–232 (2013).
Banerjee, A. et al. Renal impairment and ischemic stroke risk assessment in patients with atrial fibrillation: the Loire Valley Atrial Fibrillation Project. J. Am. College Cardiol. 61, 2079–2087 (2013).
Roldan, V. et al. Does chronic kidney disease improve the predictive value of the CHADS2 and CHA2DS2-VASc stroke stratification risk scores for atrial fibrillation? Thromb. Haemostasis 109, 956–960 (2013).
Apostolakis, S., Guo, Y., Lane, D. A., Buller, H. & Lip, G. Y. Renal function and outcomes in anticoagulated patients with non-valvular atrial fibrillation: the AMADEUS trial. Eur. Heart J. 34, 3572–3579 (2013).
Lip, G. Y., Nieuwlaat, R., Pisters, R., Lane, D. A. & Crijns, H. J. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest 137, 263–272 (2010).
Lip, G. Y. Stroke and bleeding risk assessment in atrial fibrillation: when, how, and why? Eur. Heart J. 34, 1041–1049 (2013).
Chao, T. F. et al. Incidence and prediction of ischemic stroke among atrial fibrillation patients with end-stage renal disease requiring dialysis. Heart Rhythm. 11, 1752–1759 (2014).
Wang, T. K., Sathananthan, J., Marshall, M., Kerr, A. & Hood, C. Relationships between anticoagulation, risk scores and adverse outcomes in dialysis patients with atrial fibrillation. Heart Lung Circ. 25, 243–249 (2016).
Shih, C. J. et al. Risks of death and stroke in patients undergoing hemodialysis with new-onset atrial fibrillation: a competing-risk analysis of a nationwide cohort. Circulation 133, 265–272 (2016).
Khalid, F. et al. Impact of restarting warfarin therapy in renal disease anticoagulated patients with gastrointestinal hemorrhage. Ren. Fail. 35, 1228–1235 (2013).
Murphy, M. et al. Modified HASBLED bleeding risk score in dialysis patients with atrial Fibrillation. Circulation 132, A12014 (2015).
Yoon, C. Y. et al. Warfarin use in patients with atrial fibrillation undergoing hemodialysis: a nationwide population-based study. Stroke 48, 2472–2479 (2017).
Kittelson, J. M. et al. Bivariate evaluation of thromboembolism and bleeding in clinical trials of anticoagulants in patients with atrial fibrillation. Thromb. Haemostasis 116, 544–553 (2016).
Chao, T. F. et al. Relationship of aging and incident comorbidities to stroke risk in patients with atrial fibrillation. J. Am. College Cardiol. 71, 122–132 (2018).
Esteve-Pastor, M. A. et al. Assessing bleeding risk in atrial fibrillation patients: comparing a bleeding risk score based only on modifiable bleeding risk factors against the HAS-BLED Score. The AMADEUS trial. Thromb. Haemostasis 117, 2261–2266 (2017).
Freedman, B. et al. Screening for atrial fibrillation: a report of the AF-SCREEN International Collaboration. Circulation 135, 1851–1867 (2017).
Herzog, C. A. et al. Cardiovascular disease in chronic kidney disease. A clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 80, 572–586 (2011).
Ageno, W. et al. Managing reversal of direct oral anticoagulants in emergency situations. Anticoagulation Education Task Force White Paper. Thromb. Haemostasis 116, 1003–1010 (2016).
De Caterina, R. et al. Vitamin K antagonists in heart disease: current status and perspectives (Section III). Position paper of the ESC Working Group on Thrombosis — Task Force on Anticoagulants in Heart Disease. Thromb. Haemostasis 110, 1087–1107 (2013).
Pollack, C. V. Jr. et al. Idarucizumab for dabigatran reversal. N. Engl. J. Med. 373, 511–520 (2015).
Boriani, G. et al. Chronic kidney disease in patients with cardiac rhythm disturbances or implantable electrical devices: clinical significance and implications for decision making-a position paper of the European Heart Rhythm Association endorsed by the Heart Rhythm Society and the Asia Pacific Heart Rhythm Society. Europace 17, 1169–1196 (2015).
Kefer, J. et al. Impact of chronic kidney disease on left atrial appendage occlusion for stroke prevention in patients with atrial fibrillation. Int. J. Cardiol. 207, 335–340 (2016).
Potpara, T. S. et al. Management of atrial fibrillation in patients with chronic kidney disease in Europe Results of the European Heart Rhythm Association Survey. Europace. 17, 1862–1867 (2015).
Bonde, A. N. et al. Renal function, time in therapeutic range and outcomes in warfarin-treated atrial fibrillation patients: a retrospective analysis of nationwide registries. Thromb. Haemostasis 117, 2291–2299 (2017).
US National Library of Medicine. ClinicalTrials.gov https://www.clinicaltrials.gov/ct2/show/NCT02886962 (2018).
US National Library of Medicine. ClinicalTrials.gov https://www.clinicaltrials.gov/ct2/show/NCT02933697 (2018).
US National Library of Medicine. ClinicalTrials.gov https://www.clinicaltrials.gov/ct2/show/NCT02942407 (2018).
Potpara, T. S. & Lip, G. Y. Postapproval observational studies of non-vitamin K antagonist oral anticoagulants in atrial fibrillation. JAMA 317, 1115–1116 (2017).
Pisters, R. et al. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 138, 1093–1100 (2010).
Ple, H. et al. Alteration of the platelet transcriptome in chronic kidney disease. Thromb. Haemostasis 108, 605–615 (2012).
Author information
Authors and Affiliations
Contributions
All authors researched the data for this article, wrote the text and reviewed or edited the manuscript before submission.
Corresponding author
Ethics declarations
Competing interests
G.Y.H.L. is a consultant for Bayer/Janssen, BMS/Pfizer, Biotronik, Medtronic, Boehringer Ingelheim, Novartis, Verseon and Daiichi-Sankyo and a speaker for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim and Daiichi-Sankyo. He does not personally receive any fees from these companies. T.S.P. declares no competing interests.
Glossary
- Concentric LVH
-
Increased left ventricle muscle mass in response to high pressure load (for example, due to chronic hypertension).
- Renal microinfarcts
-
Small areas of renal tissue damage due to ischaemia.
- Virchow's triad
-
The concept that three abnormalities predispose to thrombus formation: abnormal blood flow, abnormal blood constituents and abnormal vessel walls.
- Left ventricular afterload
-
The pressure against which the heart must work to eject blood during systole.
Rights and permissions
About this article
Cite this article
Potpara, T., Ferro, C. & Lip, G. Use of oral anticoagulants in patients with atrial fibrillation and renal dysfunction. Nat Rev Nephrol 14, 337–351 (2018). https://doi.org/10.1038/nrneph.2018.19
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrneph.2018.19
- Springer Nature Limited
This article is cited by
-
Clinical benefits and risks of anticoagulation therapy according to the degree of chronic kidney disease in patients with atrial fibrillation
BMC Cardiovascular Disorders (2023)
-
UK prescribing practice of anticoagulants in patients with chronic kidney disease: a nephrology and haematology-based survey
BMC Nephrology (2023)
-
Prevalence and bleeding risk associated with the concomitant use of direct oral anticoagulants and antiarrhythmic drugs in patients with atrial fibrillation, based on the French healthcare insurance database
European Journal of Clinical Pharmacology (2023)
-
Estimated glomerular filtration rate and the risk of stroke in individuals with diabetes mellitus and atrial fibrillation insight from a large contemporary population study
Journal of Thrombosis and Thrombolysis (2023)
-
Influence of renal insufficiency on anticoagulant effects and safety of warfarin in Chinese patients: analysis from a randomized controlled trial
Naunyn-Schmiedeberg's Archives of Pharmacology (2021)