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).
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).
| Outcome | Participants (studies) | Assumed risk (5 mg) | Corresponding risk (10 mg) | Relative risk (95% CI) |
|---|---|---|---|---|
| INR in-range by day 5 | 352 (4) | 571 per 1000 | 668 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 1000 | 751 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 1000 | 614 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.
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