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Novel anticoagulants for stroke prevention in atrial fibrillation: safety issues in the elderly

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Pages 677-689 | Published online: 10 Jan 2014

References

  • Go AS, Hylek EM, Phillips KA et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 285(18), 2370–2375 (2001).
  • Fuster V, Rydén LE, Cannom DS et al. ACC/AHA/ESC 2006 guidelines 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 European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 guidelines for the management of patients with atrial fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 114(7), e257–e354 (2006).
  • Lloyd-Jones DM, Wang TJ, Leip EP et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation 110(9), 1042–1046 (2004).
  • Mirza M, Strunets A, Shen WK, Jahangir A. Mechanisms of arrhythmias and conduction disorders in older adults. Clin. Geriatr. Med. 28(4), 555–73 (2012).
  • Wann LS, Curtis AB, Ellenbogen KA et al. 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (update on dabigatran): a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Heart Rhythm 8(3), e1–8 (2011).
  • Kim MH, Johnston SS, Chu BC, Dalal MR, Schulman KL. Estimation of total incremental health care costs in patients with atrial fibrillation in the United States. Circ. Cardiovasc. Qual. Outcomes 4(3), 313–320 (2011).
  • Wattigney WA, Mensah GA, Croft JB. Increased atrial fibrillation mortality: United States, 1980–1998. Am. J. Epidemiol. 155(9), 819–826 (2002).
  • Wattigney WA, Mensah GA, Croft JB. Increasing trends in hospitalization for atrial fibrillation in the United States, 1985 through 1999: implications for primary prevention. Circulation 108(6), 711–716 (2003).
  • Jahangir A, Sagar S, Terzic A. Aging and cardioprotection. J. Appl. Physiol. 103(6), 2120–2128 (2007).
  • Miyasaka Y, Barnes ME, Gersh BJ et al. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation. 114(2), 119–125. (2006).
  • Lloyd-Jones D, Adams R, Carnethon M et al. Heart disease and stroke statistics--2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 119(3), 480–486 (2009).
  • Wu EQ, Birnbaum HG, Mareva M et al. Economic burden and co-morbidities of atrial fibrillation in a privately insured population. Curr. Med. Res. Opin. 21(10), 1693–1699 (2005).
  • Dorian P, Jung W, Newman D et al. The impairment of health-related quality of life in patients with intermittent atrial fibrillation: implications for the assessment of investigational therapy. J. Am. Coll. Cardiol. 36(4), 1303–1309 (2000).
  • Lin HJ, Wolf PA, Kelly-Hayes M et al. Stroke severity in atrial fibrillation. The Framingham Study. Stroke. 27(10), 1760–1764 (1996).
  • Wang D, Hao Z, Tao W et al. Acute ischemic stroke in the very elderly Chinese: risk factors, hospital management and one-year outcome. Clin. Neurol. Neurosurg. 113(6), 442–446 (2011).
  • Poli D, Lip GY, Antonucci E, Grifoni E, Lane D. Stroke risk stratification in a “real-world” elderly anticoagulated atrial fibrillation population. J. Cardiovasc. Electrophysiol. 22(1), 25–30 (2011).
  • Lip GY, Frison L, Halperin JL, Lane DA. Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score. J. Am. Coll. Cardiol. 57(2), 173–180 (2011).
  • Heidbuchel H, Verhamme P, Alings M et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 15(5), 625–651 (2013).
  • Liew A, Eikelboom JW, O’Donnell M. Randomized controlled trials of new oral anticoagulants for stroke prevention in atrial fibrillation. Curr. Opin. Cardiol. 27(4), 331–339 (2012).
  • De Caterina R, Husted S, Wallentin L et al. New oral anticoagulants in atrial fibrillation and acute coronary syndromes: ESC Working Group on Thrombosis-Task F orce on Anticoagulants in heart disease position paper. J. Am. Coll. Cardiol. 59(16), 1413–1425 (2012).
  • Franchi C, Cartabia M, Risso P et al. Geographical differences in the prevalence of chronic polypharmacy in older people: eleven years of the EPIFARM-Elderly Project. Eur. J. Clin. Pharmacol. 69(7), 1477–1483 (2013).
  • Michalik C, Matusik P, Nowak J et al. Heart failure, comorbidities, and polypharmacy among elderly nursing home residents. Pol. Arch. Med. Wewn. 123(4), 170–175 (2013).
  • Volkert D, Pauly L, Stehle P, Sieber CC. Prevalence of malnutrition in orally and tube-fed elderly nursing home residents in Germany and its relation to health complaints and dietary intake. Gastroenterol. Res. Pract. 2011, 247315 (2011).
  • The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. N. Med. 325(2), 129–132 (1991).
  • McMillin GA, Vazquez SR, Pendleton RC. Current challenges in personalizing warfarin therapy. Expert Rev. Clin. Pharmacol. 4(3), 349–362 (2011).
  • Pautas E, Moreau C, Gouin-Thibault I et al. Genetic factors (VKORC1, CYP2C9, EPHX1, and CYP4F2) are predictor variables for warfarin response in very elderly, frail inpatients. Clin. Pharmacol. Ther. 87(1), 57–64 (2010).
  • Sconce EA, Khan TI, Wynne HA et al. The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen. Blood 106(7), 2329–2333 (2005).
  • Kamali F, Khan TI, King BP et al. Contribution of age, body size, and CYP2C9 genotype to anticoagulant response to warfarin. Clin. Pharmacol. Ther. 75(3), 204–212 (2004).
  • Lindh JD, Holm L, Andersson ML, Rane A. Influence of CYP2C9 genotype on warfarin dose requirements--a systematic review and meta-analysis. Eur. J. Clin. Pharmacol. 65(4), 365–375 (2009).
  • Jones M, McEwan P, Morgan CL, Peters JR, Goodfellow J, Currie CJ. Evaluation of the pattern of treatment, level of anticoagulation control, and outcome of treatment with warfarin in patients with non-valvar atrial fibrillation: a record linkage study in a large British population. Heart 91(4), 472–477 (2005).
  • Wadelius M, Pirmohamed M. Pharmacogenetics of warfarin: current status and future challenges. Pharmacogenomics J. 7(2), 99–111 (2007).
  • 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. Thromb. Haemost. 9(11), 2168–2175 (2011).
  • Linkins LA, Choi PT, Douketis JD. Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. Ann. Intern. Med. 139(11), 893–900 (2003).
  • Fang MC, Chang Y, Hylek EM et al. Advanced age, anticoagulation intensity, and risk for intracranial hemorrhage among patients taking warfarin for atrial fibrillation. Ann. Intern. Med. 141(10), 745–752 (2004).
  • Hylek EM, Go AS, Chang Y et al. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N. Med. 349(11), 1019–26 (2003).
  • Kubitza D, Becka M, Roth A, Mueck W. Dose-escalation study of the pharmacokinetics and pharmacodynamics of rivaroxaban in healthy elderly subjects. Curr. Med. Res. Opin. 24(10), 2757–2765 (2008).
  • Stampfuss J, Kubitza D, Becka M, Mueck W. The effect of food on the absorption and pharmacokinetics of rivaroxaban. Int. J. Clin. Pharmacol. Ther. 51(7), 549–561 (2013).
  • Kubitza D, Becka M, Mueck W, Zuehlsdorf M. Safety, tolerability, pharmacodynamics, and pharmacokinetics of rivaroxaban--an oral, direct factor Xa inhibitor--are not affected by aspirin. J. Clin. Pharmacol. 46(9), 981–990 (2006).
  • Mueck W, Eriksson BI, Bauer KA et al. Population pharmacokinetics and pharmacodynamics of rivaroxaban – an oral, direct factor Xa inhibitor – in patients undergoing major orthopaedic surgery. Clin. Pharmacokinet. 47(3), 203–216 (2008).
  • Kubitza D, Becka M, Mueck W, Zuehlsdorf M. Rivaroxaban (BAY 59–7939) – an oral, direct factor Xa inhibitor – has no clinically relevant interaction with naproxen. Br. J. Clin. Pharmacol. 63(4), 469–476 (2007).
  • Mueck W, Kubitza D, Becka M. Co-administration of rivaroxaban with drugs that share its elimination pathways: pharmacokinetic effects in healthy subjects. Br. J. Clin. Pharmacol. doi:10.1111/bcp.12075 (2013) ( Epub ahead of print).
  • Thiebaut F, Tsuruo T, Hamada H, Gottesman MM, Pastan I, Willingham MC. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc. Natl Acad. Sci. USA. 84(21), 7735–7738 (1987).
  • Gnoth MJ, Buetehorn U, Muenster U, Schwarz T, Sandmann S. In vitro and in vivo P-glycoprotein transport characteristics of rivaroxaban. J. Pharmacol. Exp. Ther. 338(1), 372–380 (2011).
  • Kubitza D, Becka M, Mueck W, Zuehlsdorf M. The effect of extreme age, and gender, on the pharmacology and tolerability of rivaroxaban – an oral, direct factor Xa inhibitor. Blood. 108, 905 (2006).
  • Burgoyne GD. What about age related decline in renal function? BMJ 344, d7916 (2011).
  • 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. Br. J. Clin. Pharmacol. 70(5), 703–712 (2010).
  • Frost C, Wang J, Nepal S et al. Apixaban, an oral, direct factor Xa inhibitor: single dose safety, pharmacokinetics, pharmacodynamics and food effect in healthy subjects. Br. J. Clin. Pharmacol. 75(2), 476–487 (2013).
  • Raghavan N, Frost CE, Yu Z et al. Apixaban metabolism and pharmacokinetics after oral administration to humans. Drug Metab. Dispos. 37(1), 74–81 (2009).
  • Granger CB, Alexander JH, McMurray JJ et al. Apixaban versus warfarin in patients with atrial fibrillation. N. Med. 365(11), 981–992 (2011).
  • Wang L, Zhang D, Raghavan N et al. In vitro assessment of metabolic drug-drug interaction potential of apixaban through cytochrome P450 phenotyping, inhibition, and induction studies. Drug Metab. Dispos. 38(3), 448–458 (2010).
  • Vakkalagadda B, Frost C, Wang J et al. Effect of rifampin on the pharmacokinetics of apixaban, an oral direct inhibitor of factor Xa. J. Clin. Pharmacol. 49(9), 1124 (2009).
  • Upreti VV, Wang J, Barrett YC et al. Effect of extremes of body weight on the pharmacokinetics, pharmacodynamics, safety and tolerability of apixaban in healthy subjects. Br. J. Clin. Pharmacol. doi:10.1111/bcp.12114 (2013) ( Epub ahead of print).
  • Granger CB, Armaganijan LV. Newer oral anticoagulants should be used as first-line agents to prevent thromboembolism in patients with atrial fibrillation and risk factors for stroke or thromboembolism. Circulation 125(1), 159–164 (2012).
  • Hohnloser SH, Hijazi Z, Thomas L 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(22), 2821–2830 (2012).
  • Eriksson BI, Quinlan DJ, Weitz JI. Comparative pharmacodynamics and pharmacokinetics of oral direct thrombin and factor Xa inhibitors in development. Clin. Pharmacokinet. 48(1), 1–22 (2009).
  • Di Nisio M, Middeldorp S, Büller HR. Direct thrombin inhibitors. N. Engl. J. Med. 353(10), 1028–1040 (2005).
  • Hazlewood KA, Weiland CM. Advances in oral anticoagulants: focus on dabigatran etexilate. Expert Rev. Clin. Pharmacol. 3(6), 727–737 (2010).
  • Stangier J, Rathgen K, Stähle H, Gansser D, Roth W. The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, a new oral direct thrombin inhibitor, in healthy male subjects. Br. J. Clin. Pharmacol. 64(3), 292–303 (2007).
  • Stangier J, Stähle H, Rathgen K, Fuhr R. Pharmacokinetics and pharmacodynamics of the direct oral thrombin inhibitor dabigatran in healthy elderly subjects. Clin. Pharmacokinet. 47(1), 47–59 (2008).
  • Trocóniz IF, Tillmann C, Liesenfeld KH, Schäfer HG, Stangier J. Population pharmacokinetic analysis of the new oral thrombin inhibitor dabigatran etexilate (BIBR 1048) in patients undergoing primary elective total hip replacement surgery. J. Clin. Pharmacol. 47(3), 371–382 (2007).
  • Connolly SJ, Ezekowitz MD, Yusuf S et al. Dabigatran versus warfarin in patients with atrial fibrillation. N. Med. 361(12), 1139–1151.
  • Ebner T, Wagner K, Wienen W. Dabigatran acylglucuronide, the major human metabolite of dabigatran: in vitro formation, stability, and pharmacological activity. Drug Metab. Dispos. 38(9), 1567–1575 (2010).
  • Freeman JV, Zhu RP, Owens DK et al. Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in atrial fibrillation. Ann. Intern. Med. 154(1), 1–11 (2011).
  • Stangier J, Rathgen K, Stähle 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(4), 259–268 (2010).
  • Dans AL, Connolly SJ, Wallentin L et al. Concomitant use of antiplatelet therapy with dabigatran or warfarin in the Randomized Evaluation of Long-Term A nticoagulation Therapy (RE-LY) trial. Circulation. 127(5), 634–640 (2013).
  • Stangier J, Stähle H, Rathgen K, Roth W, Shakeri-Nejad K. Pharmacokinetics and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor, are not affected by moderate hepatic impairment. J. Clin. Pharmacol. 48(12), 1411–1419 (2008).
  • Poli D, Antonucci E, Testa S et al. Bleeding risk in very old patients on vitamin K antagonist treatment: results of a prospective collaborative study on elderly patients followed by Italian Centres for Anticoagulation. Circulation. 124(7), 824–829 (2011).
  • Harper P, Young L, Merriman E. Bleeding risk with dabigatran in the frail elderly. N. Med. 366(9), 864–866 (2012).
  • Huisman MV, Lip GY, Diener HC, Brueckmann M, van Ryn J, Clemens A. Dabigatran etexilate for stroke prevention in patients with atrial fibrillation: resolving uncertainties in routine practice. Thromb. Haemost. 107(5), 838–847 (2012).
  • Levi M, Eerenberg E, Kamphuisen PW. Bleeding risk and reversal strategies for old and new anticoagulants and antiplatelet agents. J. Thromb. Haemost. 9(9), 1705–1712 (2011).
  • Lu G, DeGuzman FR, Hollenbach SJ et al. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat. Med. 19(4), 446–451 (2013).
  • van Ryn J, Litzenburger T, Waterman A et al. Dabigatran anticoagulant activity is neutralized by an antibody selective to dabigatran in in vitro and in vivo models free. J. Am. Coll. Cardiol. 57(14s1), E1130 (2011).
  • Ghanny S, Warkentin TE, Crowther MA. Reversing anticoagulant therapy. Curr. Drug Discov. Technol. 9(2), 143–149 (2012).
  • Levi M, Levy JH, Andersen HF, Truloff D. Safety of recombinant activated factor VII in randomized clinical trials. N. Med. 363(19), 1791–1800 (2010).
  • Dentali F, Marchesi C, Pierfranceschi MG et al. Safety of prothrombin complex concentrates for rapid anticoagulation reversal of vitamin K antagonists. A meta-analysis. Thromb. Haemost. 106(3), 429–438 (2011).
  • Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo- controlled, crossover study in healthy subjects. Circulation 124(14), 1573–1579 (2011).
  • Zhou W, Schwarting S, Illanes S et al. Hemostatic therapy in experimental intracerebral hemorrhage associated with the direct thrombin inhibitor dabigatran. Stroke 42(12), 3594–3599 (2011).
  • Furie KL, Goldstein LB, Albers GW et al. Oral antithrombotic agents for the prevention of stroke in nonvalvular atrial fibrillation: a science advisory for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 43(12), 3442–3453 (2012).

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