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Evidence summaries

Optimal Loading Dose of Warfarin for the Initiation of Oral Anticoagulation

There is insufficient evidence on the optimal loading dose of warfarin for the initiation of oral anticoagulation. Level of evidence: "D"

The quality of evidence is downgraded by study limitations (lack of/unclear allocation concealment and lack of blinding), by inconsistency (unexplained variability in results), and by imprecise results (few patients).

Summary

A Cochrane review [Abstract] 1 included 12 studies with a total of 1 656 subjects. The studies ssessed the effectiveness of different initiation doses of warfarin.

5 mg versus 10 mg (4 studies, n=355): There was no clear benefit between 10 mg versus 5 mg loading dose (Table T1).

10 mg versus 5 mg for the initiation of oral anticoagulation

OutcomeParticipants (studies)Assumed risk (5 mg)Corresponding risk (10 mg)Relative risk (95% CI)
INR in-range by day 5352 (4)571 per 1000668 per 1000 (440 to 1000)1.17 (0.77 to 1.77)
INR in-range on day 5 (single INR measure)250 (2)504 per 1000751 per 1000 (509 to 1000)1.49 (1.01 to 2.21)
INR in-range by day 5 (2 consecutive INR measures)102 (2)714 per 1000614 per 1000 (443 to 850)0.86 (0.62 to 1.19)

5 mg versus other doses (2 studies, n=322): Heart valve replacement patients (INR target 1.5 to 2.6) receiving 2.5 mg compared to 5 mg took longer to achieve the therapeutic range (2.7 versus 2.0 days, P < 0.0001) but were less likely to have a supratherapeutic INR (26% versus 42%, P < 0.05). Another study compared 5 mg with a calculated dose that took account of age, weight, serum albumin and active malignancy. Patients receiving the calculated dose achieved the target range quicker (4.2 days versus 5 days, P = 0.007), although there was no difference in other end points.

Age-adjusted: Two studies (n=192) compared age adjusted doses to 10 mg initiation doses. More elderly patients receiving an age adjusted dose achieved a stable INR compared to those receiving a 10 mg initial dose. In both studies significantly fewer patients on the age adjusted regimens had high out-of-range INRs.

Genotype loading : 4 studies (n=701) used genotype guided dosing in one arm of each trial. Three studies reported no overall differences; the fourth study, which reported that the genotype group spent significantly more time in-range (P < 0.001), had a control group whose INRs were significantly lower than expected.

Clinical comments

Note

Date of latest search:

    References

    • Mahtani KR, Heneghan CJ, Nunan D et al. Optimal loading dose of warfarin for the initiation of oral anticoagulation. Cochrane Database Syst Rev 2012;(12):CD008685. [PubMed]

Primary/Secondary Keywords