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Optimal loading dose for the initiation of warfarin: a systematic review
Carl Heneghan1, Sally Tyndel, Clare Bankhead
1Department of Primary Health Care, University of Oxford, Oxford, UK. carl.heneghan@dphpc.ox.ac.uk
BMC Cardiovascular Disorders
|April 21, 2010
Summary
Selecting the right warfarin dose is complex. Lower or age-adjusted initiation doses are best for elderly patients, while more research is needed on genotype-guided warfarin therapy.
Area of Science:
- Pharmacology and Therapeutics
- Clinical Trial Analysis
- Evidence-Based Medicine
Background:
- Initiating warfarin therapy requires careful dose selection, but optimal strategies remain unclear.
- Current evidence is insufficient to guide the best approach for starting warfarin treatment.
Purpose of the Study:
- To systematically review randomized controlled trials comparing different warfarin initiation doses and regimens.
- To evaluate the impact of various initiation strategies on time to stable International Normalized Ratio (INR) and adverse events.
Main Methods:
- Systematic review of randomized controlled trials (RCTs) identified through comprehensive database searches (Medline, EMBASE, Cochrane Library, NHS Health Economics Database) up to June 2009.
- Included patients commencing warfarin anticoagulation, comparing different loading doses or regimens.
- Primary outcomes: time to stable INR and adverse events. Results summarized as proportion of INRs in range and compared using relative risks (RR) with 95% confidence intervals (CIs).
Main Results:
- Eleven studies involving 1,340 patients were analyzed.
- A 10 mg loading dose showed potential for more patients in range on day five in some studies, but this was not consistently observed.
- Calculated initiation doses achieved therapeutic range faster (0.8 days quicker) than standard 5 mg doses.
- Age-adjusted doses in elderly patients led to more stable INRs (48% vs. 22%) and fewer high out-of-range INRs compared to the Fennerty protocol.
- No significant differences were found for genotype-guided initiation in most studies.
Conclusions:
- Considerable uncertainty persists regarding the optimal 5 mg versus 10 mg warfarin loading dose.
- Lower or age-adjusted initiation doses are recommended for elderly patients to improve INR stability and reduce high INR events.
- Insufficient evidence currently supports genotype-guided warfarin initiation; further trials are needed to assess effects on adverse events.
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