Thromboembolic consequences of subtherapeutic anticoagulation in patients stabilized on warfarin therapy: The low INR study

被引:37
作者
Clark, Nathan P. [1 ]
Witt, Daniel M. [1 ]
Delate, Thomas [2 ]
Trapp, Melissa [1 ]
Garcia, David [3 ]
Ageno, Walter [4 ]
Hylek, Elaine M. [5 ]
Crowther, Mark A. [6 ]
机构
[1] Kaiser Permanente Colorado, Clin Pharm Anticoagulat Serv, Lafayette, CO 80026 USA
[2] Kaiser Permanente Colorado, Clin Pharm Res Tearn, Lafayette, CO 80026 USA
[3] Univ New Mexico, Hlth Sci Ctr, Dept Internal Med, Albuquerque, NM 87131 USA
[4] Univ Insubria, Sch Clin Med, Varese, Italy
[5] Boston Univ, Sch Med, Dept Med, Res Unit Sect Gen Internal Med, Boston, MA 02118 USA
[6] McMaster Univ, Sch Med, Hamilton, ON L8S 4L8, Canada
来源
PHARMACOTHERAPY | 2008年 / 28卷 / 08期
关键词
vitamin K antagonist; warfarin; international normalized ratio; INR; thromboembolism; subtherapeutic anticoagulation; bridge therapy; anticoagulation management; thrombosis;
D O I
10.1592/phco.28.8.960
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Study Objective. To quantify the absolute risk of thromboembolism associated with a significant subtherapeutic international normalized ratio (INR) in patients with previously stable anticoagulation while receiving warfarin. Design. Retrospective, matched cohort analysis. Setting. Centralized anticoagulation service in an integrated health care delivery system. Patients. A total of 2597 adult patients receiving warfarin from January 1998-December 2005; 1080 patients were in the low INR cohort and were matched to 1517 patients in the therapeutic INR cohort based on index INR date, indication for warfarin, and age. Measurements and Main Results. Stable, therapeutic anticoagulation was defined as two INR values, measured at least 2 weeks apart, within or above the therapeutic range. The low INR cohort included patients with a third INR value of 0.5 or more units below their therapeutic range. The therapeutic INR cohort included patients with a third therapeutic INR value and no INR value 0.2 or more units below their target INR range in the ensuing 90 days. The primary outcome was anticoagulation-related thromboembolism during the 90 days after the index INR. Secondary outcomes were times to the first occurrence of anticoagulation-related complications (bleeding, thromboembolism, or death) in the 90 days after the index INR. Four thromboembolic events (0.4%) occurred in the low INR cohort and one event (0.1%) in the therapeutic INR cohort (p=0.214). The differences in the proportions of thromboembolism, bleeding, or death were not significant between the cohorts (p>0.05). No significant differences were noted in the hazard of thromboembolism, bleeding, or death between the cohorts (p>0.05). Conclusion. Patients with stable INRs while receiving warfarin who experience a significant subtherapeutic INR value have a low risk of thromboembolism in the ensuing 90 days. The risk was similar to that observed in a matched control population in whom therapeutic anticoagulation was maintained. These findings do not support the practice of anticoagulant bridge therapy for patients stabilized on warfarin therapy to reduce their risk for thromboembolism during isolated periods of subtherapeutic anticoagulation.
引用
收藏
页码:960 / 967
页数:8
相关论文
共 24 条
[1]   Oral anticoagulant therapy in patients with coronary artery disease: A meta-analysis [J].
Anand, SS ;
Yusuf, S .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1999, 282 (21) :2058-2067
[2]  
Blackshear JL, 1996, LANCET, V348, P633
[3]  
Booth SL, 1997, THROMB HAEMOSTASIS, V77, P504
[4]  
Cropp JS, 1997, PHARMACOTHERAPY, V17, P917
[5]   Low-molecular-weight heparin as bridging anticoagulation during interruption of warfarin [J].
Douketis, JD ;
Johnson, JA ;
Turpie, AG .
ARCHIVES OF INTERNAL MEDICINE, 2004, 164 (12) :1319-1326
[6]   The safety of warfarin therapy in the nursing home setting [J].
Gurwitz, Jerry H. ;
Field, Terry S. ;
Radford, Martha J. ;
Harrold, Leslie R. ;
Becker, Richard ;
Reed, George ;
DeBellis, Kristin ;
Moldoff, Jason ;
Verzier, Nancy .
AMERICAN JOURNAL OF MEDICINE, 2007, 120 (06) :539-544
[7]   Systematic overview of warfarin and its drug and food interactions [J].
Holbrook, AM ;
Pereira, JA ;
Labiris, R ;
McDonald, H ;
Douketis, JD ;
Crowther, M ;
Wells, PS .
ARCHIVES OF INTERNAL MEDICINE, 2005, 165 (10) :1095-1106
[8]   Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism [J].
Hutten, BA ;
Prins, MH .
COCHRANE DATABASE OF SYSTEMATIC REVIEWS, 2006, (01)
[9]   Major Hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation [J].
Hylek, Elaine M. ;
Evans-Molina, Carmella ;
Shea, Carol ;
Henault, Lori E. ;
Regan, Susan .
CIRCULATION, 2007, 115 (21) :2689-2696
[10]   An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation [J].
Hylek, EM ;
Skates, SJ ;
Sheehan, MA ;
Singer, DE .
NEW ENGLAND JOURNAL OF MEDICINE, 1996, 335 (08) :540-546