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Published in: American Journal of Cardiovascular Drugs 4/2015

01-08-2015 | Original Research Article

The Impact of Inpatient Versus Outpatient Initiation on Early Warfarin Dosing

Authors: Scott E. Kasner, Le Wang, Benjamin French, Steven R. Messe, Richard Horenstein, Emile R. Mohler III, James A. S. Muldowney III, Jonas Ellenberg, Stephen E. Kimmel

Published in: American Journal of Cardiovascular Drugs | Issue 4/2015

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Abstract

Background and Objectives

Dosing algorithms for warfarin incorporate clinical and genetic factors but may not account for the numerous comorbidities affecting patients who start warfarin while hospitalized. We aimed to determine whether these algorithms perform differently when warfarin is initiated for inpatients compared with outpatients.

Patients and Methods

We analyzed a prospective cohort of 1015 participants from the Clarification of Optimal Anticoagulation through Genetics (COAG) trial who were randomized to either pharmacogenetically or clinically guided warfarin dosing algorithms. Clinicians and participants were blinded to dose during the first 28 days. We compared groups, based on location at the time of the first warfarin dose request, in relation to the following outcomes: percentage of time in the therapeutic international normalized ratio (INR) range (PTTR) during the first 4 weeks, time to first therapeutic INR, time to maintenance dose, and the difference between predicted and observed maintenance doses.

Results

A total of 527 participants started warfarin as inpatients and 488 as outpatients. There was no difference in PTTR based on location: 43.2 % for inpatient versus 47.4 % for outpatient initiation [mean adjusted difference −2.2 %; 95 % confidence interval (CI) −5.9 to 1.6]. Similarly, there were no differences in time to first therapeutic INR [hazard ratio (HR) 1.06; 95 % CI 0.91–1.24] or to maintenance dose (HR 0.96; 95 % CI 0.81–1.14). There was no evidence of interaction between study intervention (pharmacogenetically vs. clinically guided therapy) and location of initiation for these main outcomes. The difference between predicted and observed maintenance doses was similar for both locations.

Conclusion

The warfarin dosing algorithms performed similarly for subjects who initiated warfarin as inpatients and outpatients, regardless of whether dosing was pharmacogenetically or clinically guided.
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Literature
1.
go back to reference Kimmel SE, French B, Kasner SE, Johnson JA, Anderson JL, Gage BF, Rosenberg YD, Eby CS, Madigan RA, McBane RB, Abdel-Rahman SZ, Stevens SM, Yale S, Mohler ER 3rd, Fang MC, Shah V, Horenstein RB, Limdi NA, Muldowney JA 3rd, Gujral J, Delafontaine P, Desnick RJ, Ortel TL, Billett HH, Pendleton RC, Geller NL, Halperin JL, Goldhaber SZ, Caldwell MD, Califf RM, Ellenberg JH, Investigators C. A pharmacogenetic versus a clinical algorithm for warfarin dosing. N Engl J Med. 2013;369:2283–93. doi:10.1056/NEJMoa1310669.PubMedCentralPubMedCrossRef Kimmel SE, French B, Kasner SE, Johnson JA, Anderson JL, Gage BF, Rosenberg YD, Eby CS, Madigan RA, McBane RB, Abdel-Rahman SZ, Stevens SM, Yale S, Mohler ER 3rd, Fang MC, Shah V, Horenstein RB, Limdi NA, Muldowney JA 3rd, Gujral J, Delafontaine P, Desnick RJ, Ortel TL, Billett HH, Pendleton RC, Geller NL, Halperin JL, Goldhaber SZ, Caldwell MD, Califf RM, Ellenberg JH, Investigators C. A pharmacogenetic versus a clinical algorithm for warfarin dosing. N Engl J Med. 2013;369:2283–93. doi:10.​1056/​NEJMoa1310669.PubMedCentralPubMedCrossRef
2.
go back to reference Anderson JL, Horne BD, Stevens SM, Grove AS, Barton S, Nicholas ZP, Kahn SF, May HT, Samuelson KM, Muhlestein JB, Carlquist JF, Couma-Gen I. Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation. Circulation. 2007;116:2563–70. doi:10.1161/CIRCULATIONAHA.107.737312.PubMedCrossRef Anderson JL, Horne BD, Stevens SM, Grove AS, Barton S, Nicholas ZP, Kahn SF, May HT, Samuelson KM, Muhlestein JB, Carlquist JF, Couma-Gen I. Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation. Circulation. 2007;116:2563–70. doi:10.​1161/​CIRCULATIONAHA.​107.​737312.PubMedCrossRef
3.
go back to reference Anderson JL, Horne BD, Stevens SM, Woller SC, Samuelson KM, Mansfield JW, Robinson M, Barton S, Brunisholz K, Mower CP, Huntinghouse JA, Rollo JS, Siler D, Bair TL, Knight S, Muhlestein JB, Carlquist JF. A randomized and clinical effectiveness trial comparing two pharmacogenetic algorithms and standard care for individualizing warfarin dosing (CoumaGen-II). Circulation. 2012;125:1997–2005. doi:10.1161/CIRCULATIONAHA.111.070920.PubMedCrossRef Anderson JL, Horne BD, Stevens SM, Woller SC, Samuelson KM, Mansfield JW, Robinson M, Barton S, Brunisholz K, Mower CP, Huntinghouse JA, Rollo JS, Siler D, Bair TL, Knight S, Muhlestein JB, Carlquist JF. A randomized and clinical effectiveness trial comparing two pharmacogenetic algorithms and standard care for individualizing warfarin dosing (CoumaGen-II). Circulation. 2012;125:1997–2005. doi:10.​1161/​CIRCULATIONAHA.​111.​070920.PubMedCrossRef
4.
go back to reference Gage BF, Eby C, Johnson JA, Deych E, Rieder MJ, Ridker PM, Milligan PE, Grice G, Lenzini P, Rettie AE, Aquilante CL, Grosso L, Marsh S, Langaee T, Farnett LE, Voora D, Veenstra DL, Glynn RJ, Barrett A, McLeod HL. Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin. Clin Pharmacol Ther. 2008;84:326–31. doi:10.1038/clpt.2008.10.PubMedCentralPubMedCrossRef Gage BF, Eby C, Johnson JA, Deych E, Rieder MJ, Ridker PM, Milligan PE, Grice G, Lenzini P, Rettie AE, Aquilante CL, Grosso L, Marsh S, Langaee T, Farnett LE, Voora D, Veenstra DL, Glynn RJ, Barrett A, McLeod HL. Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin. Clin Pharmacol Ther. 2008;84:326–31. doi:10.​1038/​clpt.​2008.​10.PubMedCentralPubMedCrossRef
5.
go back to reference Lenzini P, Wadelius M, Kimmel S, Anderson JL, Jorgensen AL, Pirmohamed M, Caldwell MD, Limdi N, Burmester JK, Dowd MB, Angchaisuksiri P, Bass AR, Chen J, Eriksson N, Rane A, Lindh JD, Carlquist JF, Horne BD, Grice G, Milligan PE, Eby C, Shin J, Kim H, Kurnik D, Stein CM, McMillin G, Pendleton RC, Berg RL, Deloukas P, Gage BF. Integration of genetic, clinical, and INR data to refine warfarin dosing. Clin Pharmacol Ther. 2010;87:572–8. doi:10.1038/clpt.2010.13.PubMedCentralPubMedCrossRef Lenzini P, Wadelius M, Kimmel S, Anderson JL, Jorgensen AL, Pirmohamed M, Caldwell MD, Limdi N, Burmester JK, Dowd MB, Angchaisuksiri P, Bass AR, Chen J, Eriksson N, Rane A, Lindh JD, Carlquist JF, Horne BD, Grice G, Milligan PE, Eby C, Shin J, Kim H, Kurnik D, Stein CM, McMillin G, Pendleton RC, Berg RL, Deloukas P, Gage BF. Integration of genetic, clinical, and INR data to refine warfarin dosing. Clin Pharmacol Ther. 2010;87:572–8. doi:10.​1038/​clpt.​2010.​13.PubMedCentralPubMedCrossRef
6.
go back to reference Pautas E, Moreau C, Gouin-Thibault I, Golmard JL, Mahe I, Legendre C, Taillandier-Heriche E, Durand-Gasselin B, Houllier AM, Verrier P, Beaune P, Loriot MA, Siguret V. Genetic factors (VKORC1, CYP2C9, EPHX1, and CYP4F2) are predictor variables for warfarin response in very elderly, frail inpatients. Clin Pharmacol Ther. 2010;87:57–64. doi:10.1038/clpt.2009.178.PubMedCrossRef Pautas E, Moreau C, Gouin-Thibault I, Golmard JL, Mahe I, Legendre C, Taillandier-Heriche E, Durand-Gasselin B, Houllier AM, Verrier P, Beaune P, Loriot MA, Siguret V. Genetic factors (VKORC1, CYP2C9, EPHX1, and CYP4F2) are predictor variables for warfarin response in very elderly, frail inpatients. Clin Pharmacol Ther. 2010;87:57–64. doi:10.​1038/​clpt.​2009.​178.PubMedCrossRef
7.
go back to reference Siguret V, Gouin I, Debray M, Perret-Guillaume C, Boddaert J, Mahe I, Donval V, Seux ML, Romain-Pilotaz M, Gisselbrecht M, Verny M, Pautas E. Initiation of warfarin therapy in elderly medical inpatients: a safe and accurate regimen. Am J Med. 2005;118:137–42. doi:10.1016/j.amjmed.2004.07.053.PubMedCrossRef Siguret V, Gouin I, Debray M, Perret-Guillaume C, Boddaert J, Mahe I, Donval V, Seux ML, Romain-Pilotaz M, Gisselbrecht M, Verny M, Pautas E. Initiation of warfarin therapy in elderly medical inpatients: a safe and accurate regimen. Am J Med. 2005;118:137–42. doi:10.​1016/​j.​amjmed.​2004.​07.​053.PubMedCrossRef
8.
go back to reference Dager WE, Branch JM, King JH, White RH, Quan RS, Musallam NA, Albertson TE. Optimization of inpatient warfarin therapy: impact of daily consultation by a pharmacist-managed anticoagulation service. Ann Pharmacother. 2000;34:567–72.PubMedCrossRef Dager WE, Branch JM, King JH, White RH, Quan RS, Musallam NA, Albertson TE. Optimization of inpatient warfarin therapy: impact of daily consultation by a pharmacist-managed anticoagulation service. Ann Pharmacother. 2000;34:567–72.PubMedCrossRef
9.
go back to reference Dawson NL, Porter IE 2nd, Klipa D, Bamlet WR, Hedges MA, Maniaci MJ, Persoff J, Roy A, Patel AV. Inpatient warfarin management: pharmacist management using a detailed dosing protocol. J Thromb Thrombolysis. 2012;33:178–84. doi:10.1007/s11239-011-0655-9.PubMedCrossRef Dawson NL, Porter IE 2nd, Klipa D, Bamlet WR, Hedges MA, Maniaci MJ, Persoff J, Roy A, Patel AV. Inpatient warfarin management: pharmacist management using a detailed dosing protocol. J Thromb Thrombolysis. 2012;33:178–84. doi:10.​1007/​s11239-011-0655-9.PubMedCrossRef
10.
go back to reference Fowler S, Gulseth MP, Renier C, Tomsche J. Inpatient warfarin: experience with a pharmacist-led anticoagulation management service in a tertiary care medical center. Am J Health Syst Pharm. 2012;69:44–8. doi:10.2146/ajhp110015.PubMedCrossRef Fowler S, Gulseth MP, Renier C, Tomsche J. Inpatient warfarin: experience with a pharmacist-led anticoagulation management service in a tertiary care medical center. Am J Health Syst Pharm. 2012;69:44–8. doi:10.​2146/​ajhp110015.PubMedCrossRef
11.
go back to reference Maynard G, Humber D, Jenkins I. Multidisciplinary initiative to improve inpatient anticoagulation and management of venous thromboembolism. Am J Health Syst Pharm. 2014;71:305–10. doi:10.2146/ajhp130108.PubMedCrossRef Maynard G, Humber D, Jenkins I. Multidisciplinary initiative to improve inpatient anticoagulation and management of venous thromboembolism. Am J Health Syst Pharm. 2014;71:305–10. doi:10.​2146/​ajhp130108.PubMedCrossRef
13.
go back to reference French B, Joo J, Geller NL, Kimmel SE, Rosenberg Y, Anderson JL, Gage BF, Johnson JA, Ellenberg JH, Investigators C. Statistical design of personalized medicine interventions: the Clarification of Optimal Anticoagulation through Genetics (COAG) trial. Trials. 2010;11:108. doi:10.1186/1745-6215-11-108.PubMedCentralPubMedCrossRef French B, Joo J, Geller NL, Kimmel SE, Rosenberg Y, Anderson JL, Gage BF, Johnson JA, Ellenberg JH, Investigators C. Statistical design of personalized medicine interventions: the Clarification of Optimal Anticoagulation through Genetics (COAG) trial. Trials. 2010;11:108. doi:10.​1186/​1745-6215-11-108.PubMedCentralPubMedCrossRef
14.
go back to reference Kimmel SE, French B, Anderson JL, Gage BF, Johnson JA, Rosenberg YD, Geller NL, Kasner SE, Eby CS, Joo J, Caldwell MD, Goldhaber SZ, Hart RG, Cifelli D, Madigan R, Brensinger CM, Goldberg S, Califf RM, Ellenberg JH. Rationale and design of the Clarification of Optimal Anticoagulation through Genetics trial. Am Heart J. 2013;166:435–41. doi:10.1016/j.ahj.2013.04.009.PubMedCentralPubMedCrossRef Kimmel SE, French B, Anderson JL, Gage BF, Johnson JA, Rosenberg YD, Geller NL, Kasner SE, Eby CS, Joo J, Caldwell MD, Goldhaber SZ, Hart RG, Cifelli D, Madigan R, Brensinger CM, Goldberg S, Califf RM, Ellenberg JH. Rationale and design of the Clarification of Optimal Anticoagulation through Genetics trial. Am Heart J. 2013;166:435–41. doi:10.​1016/​j.​ahj.​2013.​04.​009.PubMedCentralPubMedCrossRef
15.
go back to reference Rosendaal FR, Cannegieter SC, van der Meer FJ, Briet E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost. 1993;69:236–9.PubMed Rosendaal FR, Cannegieter SC, van der Meer FJ, Briet E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost. 1993;69:236–9.PubMed
16.
go back to reference Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G, American College of Chest Physicians. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133:160S–98S. doi:10.1378/chest.08-0670.PubMedCrossRef Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G, American College of Chest Physicians. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133:160S–98S. doi:10.​1378/​chest.​08-0670.PubMedCrossRef
17.
go back to reference Johnson JA, Gong L, Whirl-Carrillo M, Gage BF, Scott SA, Stein CM, Anderson JL, Kimmel SE, Lee MT, Pirmohamed M, Wadelius M, Klein TE, Altman RB, Clinical Pharmacogenetics Implementation Consortium. Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing. Clin Pharmacol Ther. 2011;90:625–9. doi:10.1038/clpt.2011.185.PubMedCentralPubMedCrossRef Johnson JA, Gong L, Whirl-Carrillo M, Gage BF, Scott SA, Stein CM, Anderson JL, Kimmel SE, Lee MT, Pirmohamed M, Wadelius M, Klein TE, Altman RB, Clinical Pharmacogenetics Implementation Consortium. Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing. Clin Pharmacol Ther. 2011;90:625–9. doi:10.​1038/​clpt.​2011.​185.PubMedCentralPubMedCrossRef
18.
go back to reference Pirmohamed M, Burnside G, Eriksson N, Jorgensen AL, Toh CH, Nicholson T, Kesteven P, Christersson C, Wahlstrom B, Stafberg C, Zhang JE, Leathart JB, Kohnke H, Maitland-van der Zee AH, Williamson PR, Daly AK, Avery P, Kamali F, Wadelius M, Group E-P. A randomized trial of genotype-guided dosing of warfarin. N Engl J Med. 2013;369:2294–303. doi:10.1056/NEJMoa1311386.PubMedCrossRef Pirmohamed M, Burnside G, Eriksson N, Jorgensen AL, Toh CH, Nicholson T, Kesteven P, Christersson C, Wahlstrom B, Stafberg C, Zhang JE, Leathart JB, Kohnke H, Maitland-van der Zee AH, Williamson PR, Daly AK, Avery P, Kamali F, Wadelius M, Group E-P. A randomized trial of genotype-guided dosing of warfarin. N Engl J Med. 2013;369:2294–303. doi:10.​1056/​NEJMoa1311386.PubMedCrossRef
Metadata
Title
The Impact of Inpatient Versus Outpatient Initiation on Early Warfarin Dosing
Authors
Scott E. Kasner
Le Wang
Benjamin French
Steven R. Messe
Richard Horenstein
Emile R. Mohler III
James A. S. Muldowney III
Jonas Ellenberg
Stephen E. Kimmel
Publication date
01-08-2015
Publisher
Springer International Publishing
Published in
American Journal of Cardiovascular Drugs / Issue 4/2015
Print ISSN: 1175-3277
Electronic ISSN: 1179-187X
DOI
https://doi.org/10.1007/s40256-015-0126-3

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