Anticoagulation – Optimal loading dose of warfarin for the initiation of oral anticoagulation

KM1Warfarin is commonly prescribed to prevent blot clots in patients with medical conditions such as atrial fibrillation, heart valve replacement or previous blood clots. Warfarin is an effective treatment which has been used for many years but needs to be closely monitored, especially at the beginning of treatment, as there is a wide variation in response to dose. Monitoring of the response to dose is done using an International Normalized Ratio (INR) and it is important that patients remain within a narrow range (typically 2 to 3 INR) due to the need to balance the goal of preventing blood clots with the risk of causing excessive bleeding.

Our review included 12 randomised controlled trials comparing different warfarin doses given to patients beginning warfarin treatment. Most of the studies had a high risk of bias so the results were interpreted with caution. Those trials that were included compared loading doses in several different situations. The review divided the trials into four categories, 5 mg versus 10 mg initial doses (four studies), 5 mg versus other doses (two studies), 5 mg or 10 mg versus age adjusted doses (two studies), 5 mg or 10 mg versus genotype adjusted doses (four studies).

We concluded that there is still considerable uncertainty between the use of a 5 mg and a 10 mg loading dose for the initiation of warfarin. In the elderly, there was some evidence that lower initiation doses or age adjusted doses are were more appropriate.

However, we found insufficient evidence to warrant genotype adjusted dosing. We also found no data to suggest that any one method was safer than another.

Impact
The reviews have been cited by the British Committee for Standards in Haematology Guidelines on oral anticoagulation with warfarin
The review has also been cited by NICE in there clinical knowledge summaries on anticoagulation

Publications

Associated media
Evidently Cochrane – Loading with warfarin, what’s the quickest and safest dose?