CMAJ • July 29, 2008; 179 (3). doi:10.1503/cmaj.080171.
© 2008 Canadian Medical Association or its licensors
All editorial matter in CMAJ represents the opinions of the authors and not necessarily those of the Canadian Medical Association.
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Résumé
Right arrow Online Appendices
Right arrow Submit a response
Right arrow View responses
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Oake, N.
Right arrow Articles by van Walraven, C.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Oake, N., MSc
Right arrow Articles by van Walraven, C., MD MSc
Related Collections
Right arrow Drugs: cardiovascular system
Right arrow Adverse drug reactions
Right arrow Hematologic pathology (including blood transfusion)
Right arrowRelated Article

Research

Anticoagulation intensity and outcomes among patients prescribed oral anticoagulant therapy: a systematic review and meta-analysis

Natalie Oake, MSc, Alison Jennings, MA, Alan J. Forster, MD MSc, Dean Fergusson, PhD, Steve Doucette, MSc and Carl van Walraven, MD MSc

From the Department of Medicine, University of Ottawa, and the Clinical Epidemiology Program, Ottawa Health Research Institute (Oake, Jennings, Forster, Fergusson, Doucette, van Walraven), Ottawa, Ont.; and the Institute for Clinical Evaluative Sciences (van Walraven), Toronto, Ont.

Correspondence to: Dr. Carl van Walraven, Clinical Epidemiology Program, Ottawa Health Research Institute, Rm. ASB1-003, Ottawa Hospital, Civic Campus, 1053 Carling Ave., Ottawa ON K1Y 4E9; fax 613 761-5355; carlv{at}ohri.ca

Background: Patients taking oral anticoagulant therapy balance the risks of hemorrhage and thromboembolism. We sought to determine the association between anticoagulation intensity and the risk of hemorrhagic and thromboembolic events. We also sought to determine how under-or overanticoagulation would influence patient outcomes.

Methods: We reviewed the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and CINAHL databases to identify studies involving patients taking anticoagulants that reported person-years of observation and the number of hemorrhages or thromboemboli in 3 or more discrete ranges of international normalized ratios. We estimated the overall relative and absolute risks of events specific to anticoagulation intensity.

Results: We included 19 studies. The risk of hemorrhage increased significantly at high international normalized ratios. Compared with the therapeutic ratio of 2–3, the relative risk (RR) of hemorrhage (and 95% confidence intervals [CIs]) were 2.7 (1.8–3.9; p < 0.01) at a ratio of 3–5 and 21.8 (12.1–39.4; p < 0.01) at a ratio greater than 5. The risk of thromboemboli increased significantly at ratios less than 2, with a relative risk of 3.5 (95% CI 2.8–4.4; p < 0.01). The risk of hemorrhagic or thromboembolic events was lower at ratios of 3–5 (RR 1.8, 95% CI 1.2–2.6) than at ratios of less than 2 (RR 2.4, 95% CI 1.9–3.1; p = 0.10). We found that a ratio of 2–3 had the lowest absolute risk (AR) of events (AR 4.3%/yr, 95% CI 3.0%–6.3%).

Conclusions: The risks of hemorrhage and thromboemboli are minimized at international normalized ratios of 2–3. Ratios that are moderately higher than this therapeutic range appear safe and more effective than subtherapeutic ratios.


Related Article

A higher international normalized ratio may be better for your patient
Harry Buller, MD
Can. Med. Assoc. J. 2008 179: 217. [Full Text] [PDF]



This article has been cited by other articles:


Home page
 Circ Cardiovasc Qual OutcomesHome page
D. E. Singer, Y. Chang, M. C. Fang, L. H. Borowsky, N. K. Pomernacki, N. Udaltsova, and A. S. Go
Should Patient Characteristics Influence Target Anticoagulation Intensity for Stroke Prevention in Nonvalvular Atrial Fibrillation?: The ATRIA Study
Circ Cardiovasc Qual Outcomes, July 1, 2009; 2(4): 297 - 304.
[Abstract] [Full Text] [PDF]

Home page
 CMAJHome page
N. Oake, C. van Walraven, M. A. Rodger, and A. J. Forster
Effect of an interactive voice response system on oral anticoagulant management
Can. Med. Assoc. J., April 28, 2009; 180(9): 927 - 933.
[Abstract] [Full Text] [PDF]

Home page
 CMAJHome page
H. Buller MD
A higher international normalized ratio may be better for your patient
Can. Med. Assoc. J., July 29, 2008; 179(3): 217 - 217.
[Full Text] [PDF]

eLetters:

Read all eLetters

Anticoagulation is indicated in all patients with high risk of thromboembolism regardless of age
Radhakrishnan Ramaraj
CMAJ, 12 Aug 2008 [Full text]