心房颤动合并慢性肾脏疾病患者口服抗凝的治疗策略
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摘要
口服抗凝药物(oral anticoagulants,OACs)在预防心房颤动(atrial fibrillation,AF)导致的卒中和全身栓塞性疾病中发挥着重要作用,被广泛用于缺血中、高危的AF患者。AF大多同时合并慢性肾脏疾病(chronic kidney disease,CKD)。严重肾功能不全是AF患者发生卒中的独立危险因素,同时肾功能不全对OACs的体内处置也会产生不同程度的影响。因此,临床上对AF合并CKD患者的口服抗凝治疗方案需要更加谨慎。本文拟综述国内已批准的OACs在AF合并CKD患者的药代动力学变化及安全有效性,为指导临床上OACs的合理使用提供依据。
Oral anticoagulants(OACs) have been widely used in patients with atrial fibrillation(AF) who have moderate or high risk of thromboembolism to reduce stroke and systemic embolism.AF and chronic kidney disease(CKD) frequently coexist.Stage 3 CKD is an independent risk factor for stroke in patients with AF.Besides,all OACs undergo renal clearance to varying degrees,and hence dosing,efficacy,and safety require special consideration in patients with CKD.This review is intended to explore the pharmacokinetic changes and safety and efficacy of approved OACs in patients with AF and CKD.Based on this,the OACs selection scheme and dose recommendation for this population are provided,in order to provide guidance for the rational use of OACs.
Oral anticoagulants(OACs) have been widely used in patients with atrial fibrillation(AF) who have moderate or high risk of thromboembolism to reduce stroke and systemic embolism.AF and chronic kidney disease(CKD) frequently coexist.Stage 3 CKD is an independent risk factor for stroke in patients with AF.Besides,all OACs undergo renal clearance to varying degrees,and hence dosing,efficacy,and safety require special consideration in patients with CKD.This review is intended to explore the pharmacokinetic changes and safety and efficacy of approved OACs in patients with AF and CKD.Based on this,the OACs selection scheme and dose recommendation for this population are provided,in order to provide guidance for the rational use of OACs.
引文
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[2] Olesen JB,Lip GY,Kamper AL,et al.Stroke and bleeding in atrial fibrillation with chronic kidney disease[J].N Engl J Med,2012,367(7):625-635.
[3] 黄从新,张澍,黄德嘉,等.心房颤动:目前的认识和治疗建议-2015[J].中国心脏起搏与心电生理杂志,2015,29(5):377-434.
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[13] Eiser AR.Warfarin,calciphylaxis,atrial fibrillation,and patients on dialysis:outlier subsets and practice guidelines[J].Am J Med,2014,127(4):253-254.
[14] Wheeler DS,Giugliano RP.Rangaswami J.Anticoagulation-related nephropathy[J].J Thromb Haemost,2016,14(3):461-467.
[15] Liesenfeld KH,Lehr T,Dansirikul C,et al.Population pharmacokinetic analysis of the oral thrombin inhibitor dabigatran etexilate in patients with non-valvular atrial fibrillation from the RE-LY trial[J].J Thromb Haemost,2011,9(11):2168-2175.
[16] Stangier J,Rathgen K,St?hle H,et al.Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate:an open-label,parallel-group,single-centre study[J].Clin Pharmacokinet,2010,49(4):259-268.
[17] Kooiman J,van der Hulle T,Maas H,et al.Pharmacokinetics and Pharmacodynamics of Dabigatran 75 mg b.i.d.in Patients With Severe Chronic Kidney Disease[J].J Am Coll Cardiol,2016,67(20):2442-2444.
[18] Ribes-Cruz JJ,Torregrosa-Maicas I,Ramos-Tomas C,et al.Dabigatran-induced upper intestinal bleeding in a patient with chronic kidney disease[J].Nefrologia,2013,33(6):864-866.
[19] Hijazi Z,Hohnloser SH,Oldgren J,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[J].Circulation,2014,129(9):961-970.
[20] Romanelli RJ,Nolting L,Dolginsky M,et al.Dabigatran Versus Warfarin for Atrial Fibrillation in Real-World Clinical Practice:A Systematic Review and Meta-Analysis[J].Circ Cardiovasc Qual Outcomes,2016,9(2):126-134.
[21] Lauffenburger JC,Farley JF,Gehi AK,et al.Effectiveness and safety of dabigatran and warfarin in real-world US patients with non-valvular atrial fibrillation:a retrospective cohort study[J].J Am Heart Assoc,2015,4(4):e001798.
[22] Hernandez I,Zhang Y.Risk of Bleeding With Dabigatran in 2010-2011 Medicare Data[J].JAMA Intern Med,2015,175(7):1245-1247.
[23] Graham DJ,Reichman ME,Wernecke M,et al.Cardiovascular,bleeding,and mortality risks in elderly Medicare patients treated with dabigatran or warfarin for nonvalvular atrial fibrillation[J].Circulation,2015,131(2):157-164.
[24] Chan KE,Edelman ER,Wenger JB,et al.Dabigatran and rivaroxaban use in atrial fibrillation patients on hemodialysis[J].Circulation,2015,131(11):972-979.
[25] Matsumoto M,Hori M,Tanahashi N,et al.Rivaroxaban versus warfarin in Japanese patients with non-valvular atrial fibrillation in relation to hypertension:a subgroup analysis of the J-ROCKET AF trial[J].Hypertens Res,2014,37(5):457-462.
[26] Kubitza D,Becka M,Mueck W,et al.Effects of renal impairment on the pharmacokinetics,pharmacodynamics and safety of rivaroxaban,an oral,direct Factor Ⅹa inhibitor[J].Br J Clin Pharmacol,2010,70(5):703-712.
[27] De Vriese AS,Caluwé R,Bailleul E,et al.Dose-finding study of rivaroxaban in hemodialysis patients[J].Am J Kidney Dis,2015,66(1):91-98.
[28] Dias C,Moore KT,Murphy J,et al.Pharmacokinetics,Pharmacodynamics,and Safety of Single-Dose Rivaroxaban in Chronic Hemodialysis[J].Am J Nephrol,2016,43(4):229-236.
[29] Granger CB,Alexander JH,Mcmurray JJ,et al.Apixaban versus warfarin in patients with atrial fibrillation[J].N Engl J Med,2011,365(11):981-992.
[30] Chang M,Yu Z,Shenker A,et al.Effect of renal impairment on the pharmacokinetics,pharmacodynamics,and safety of apixaban[J].J Clin Pharmacol,2016,56(5):637-645.
[31] Steuber TD,Shiltz DL,Cairns AC,et al.A Multicenter Analysis of Factors Associated With Apixaban-Related Bleeding in Hospitalized Patients With End-Stage Renal Disease on Hemodialysis[J].Ann Pharmacother,2017,51(11):954-960.
[32] Sarratt SC,Nesbit R.Moye R.Safety Outcomes of Apixaban Compared With Warfarin in Patients With End-Stage Renal Disease[J].Ann Pharmacother,2017,51(6):445-450.
[33] 中国慢性肾脏病患者合并高尿酸血症诊治共识专家组.中国慢性肾脏病患者合并高尿酸血症诊治专家共识[J].中华肾脏病杂志,2017,33(6):463-469. (收稿日期:2018-08-28)
[2] Olesen JB,Lip GY,Kamper AL,et al.Stroke and bleeding in atrial fibrillation with chronic kidney disease[J].N Engl J Med,2012,367(7):625-635.
[3] 黄从新,张澍,黄德嘉,等.心房颤动:目前的认识和治疗建议-2015[J].中国心脏起搏与心电生理杂志,2015,29(5):377-434.
[4] Owen RP,Gong L,Sagreiya H,et al.VKORC1 pharmacogenomics summary[J].Pharmacogenet Genomics,2010,20(10):642-644.
[5] Ansell J,Hirsh J,Hylek E,et al.Pharmacology and management of the vitamin k antagonists:american college of chest physicians evidence-based clinical practice guidelines (8th Edition)[J].Chest,2008,133(6 Suppl):160S-198S.
[6] Harder S.Renal profiles of anticoagulants[J].J Clin Pharmacol,2012,52(7):964-975.
[7] Limdi NA,Beasley TM,Baird MF,et al.Kidney function influences warfarin responsiveness and hemorrhagic complications[J].J Am Soc Nephrol,2009,20(4):912-921.
[8] Limdi NA,Limdi MA,Cavallari L,et al.Warfarin dosing in patients with impaired kidney function[J].Am J Kidney Dis,2010,56(5):823-831.
[9] January CT,Wann LS,Alpert JS,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].J Am Coll Cardiol,2014,64(21):e1-76.
[10] Nolin TD,Frye RF,Le P,et al.ESRD impairs nonrenal clearance of fexofenadine but not midazolam[J].J Am Soc Nephrol,2009,20(10):2269-2276.
[11] Limdi NA,Nolin TD,Booth SL,et al.Influence of kidney function on risk of supratherapeutic international normalized ratio-related hemorrhage in warfarin users:a prospective cohort study[J].Am J Kidney Dis,2015,65(5):701-709.
[12] Yalamanchili V,Reilly RF.Does the risk exceed the benefit for anticoagulation in end-stage renal disease patients with nonrheumatic atrial fibrillation?[J].Semin Dial,2011,24(4):387-388.
[13] Eiser AR.Warfarin,calciphylaxis,atrial fibrillation,and patients on dialysis:outlier subsets and practice guidelines[J].Am J Med,2014,127(4):253-254.
[14] Wheeler DS,Giugliano RP.Rangaswami J.Anticoagulation-related nephropathy[J].J Thromb Haemost,2016,14(3):461-467.
[15] Liesenfeld KH,Lehr T,Dansirikul C,et al.Population pharmacokinetic analysis of the oral thrombin inhibitor dabigatran etexilate in patients with non-valvular atrial fibrillation from the RE-LY trial[J].J Thromb Haemost,2011,9(11):2168-2175.
[16] Stangier J,Rathgen K,St?hle H,et al.Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate:an open-label,parallel-group,single-centre study[J].Clin Pharmacokinet,2010,49(4):259-268.
[17] Kooiman J,van der Hulle T,Maas H,et al.Pharmacokinetics and Pharmacodynamics of Dabigatran 75 mg b.i.d.in Patients With Severe Chronic Kidney Disease[J].J Am Coll Cardiol,2016,67(20):2442-2444.
[18] Ribes-Cruz JJ,Torregrosa-Maicas I,Ramos-Tomas C,et al.Dabigatran-induced upper intestinal bleeding in a patient with chronic kidney disease[J].Nefrologia,2013,33(6):864-866.
[19] Hijazi Z,Hohnloser SH,Oldgren J,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[J].Circulation,2014,129(9):961-970.
[20] Romanelli RJ,Nolting L,Dolginsky M,et al.Dabigatran Versus Warfarin for Atrial Fibrillation in Real-World Clinical Practice:A Systematic Review and Meta-Analysis[J].Circ Cardiovasc Qual Outcomes,2016,9(2):126-134.
[21] Lauffenburger JC,Farley JF,Gehi AK,et al.Effectiveness and safety of dabigatran and warfarin in real-world US patients with non-valvular atrial fibrillation:a retrospective cohort study[J].J Am Heart Assoc,2015,4(4):e001798.
[22] Hernandez I,Zhang Y.Risk of Bleeding With Dabigatran in 2010-2011 Medicare Data[J].JAMA Intern Med,2015,175(7):1245-1247.
[23] Graham DJ,Reichman ME,Wernecke M,et al.Cardiovascular,bleeding,and mortality risks in elderly Medicare patients treated with dabigatran or warfarin for nonvalvular atrial fibrillation[J].Circulation,2015,131(2):157-164.
[24] Chan KE,Edelman ER,Wenger JB,et al.Dabigatran and rivaroxaban use in atrial fibrillation patients on hemodialysis[J].Circulation,2015,131(11):972-979.
[25] Matsumoto M,Hori M,Tanahashi N,et al.Rivaroxaban versus warfarin in Japanese patients with non-valvular atrial fibrillation in relation to hypertension:a subgroup analysis of the J-ROCKET AF trial[J].Hypertens Res,2014,37(5):457-462.
[26] Kubitza D,Becka M,Mueck W,et al.Effects of renal impairment on the pharmacokinetics,pharmacodynamics and safety of rivaroxaban,an oral,direct Factor Ⅹa inhibitor[J].Br J Clin Pharmacol,2010,70(5):703-712.
[27] De Vriese AS,Caluwé R,Bailleul E,et al.Dose-finding study of rivaroxaban in hemodialysis patients[J].Am J Kidney Dis,2015,66(1):91-98.
[28] Dias C,Moore KT,Murphy J,et al.Pharmacokinetics,Pharmacodynamics,and Safety of Single-Dose Rivaroxaban in Chronic Hemodialysis[J].Am J Nephrol,2016,43(4):229-236.
[29] Granger CB,Alexander JH,Mcmurray JJ,et al.Apixaban versus warfarin in patients with atrial fibrillation[J].N Engl J Med,2011,365(11):981-992.
[30] Chang M,Yu Z,Shenker A,et al.Effect of renal impairment on the pharmacokinetics,pharmacodynamics,and safety of apixaban[J].J Clin Pharmacol,2016,56(5):637-645.
[31] Steuber TD,Shiltz DL,Cairns AC,et al.A Multicenter Analysis of Factors Associated With Apixaban-Related Bleeding in Hospitalized Patients With End-Stage Renal Disease on Hemodialysis[J].Ann Pharmacother,2017,51(11):954-960.
[32] Sarratt SC,Nesbit R.Moye R.Safety Outcomes of Apixaban Compared With Warfarin in Patients With End-Stage Renal Disease[J].Ann Pharmacother,2017,51(6):445-450.
[33] 中国慢性肾脏病患者合并高尿酸血症诊治共识专家组.中国慢性肾脏病患者合并高尿酸血症诊治专家共识[J].中华肾脏病杂志,2017,33(6):463-469. (收稿日期:2018-08-28)