Key message: There is not enough evidence to show whether 10mg or 5mg loading dose of warfarin is safer or quicker. It may be more appropriate to use smaller doses in elderly patients.
Warfarin is a well established oral anticoagulant used all over the world for Something done with the aim of improving health or relieving suffering. For example, medicines, surgery, psychological and physical therapies, diet and exercise changes. and prevention of blood clots. One of the challenges of prescribing this drug is the variation in patient response to warfarin (some patients require two or three times larger doses than others for the same effect). The other challenge is the dose delay, usually of a few days, between taking warfarin and its blood thinning effect. This leads to delays in reaching its therapeutic threshold and can lead to unstable and elevated INR levels, raising the A way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. of bleeding complications.
A new review from the Cochrane Heart Group has now been published, comparing warfarin doses for patients beginning treatment.The review included 12 studies. Four studies compared 5mg and 10mg loading doses, four studies comparing genotype guided dosing, two comparing age adjusted doses to 10mg doses, one An investigation of a healthcare problem. There are different types of studies used to answer research questions, for example randomised controlled trials or observational studies. compared 5mg and 2.5mg doses and one compared a calculated initiation dose to 5mg.
What did they find?
- There was no significant difference between the 5mg and 10mg dose loading groups
- When 2.5mg loading dose was compared to 5mg it was found to take longer to reach the target range
- When an age adjusted dose was used in elderly patients compared to a 10mg loading dose, more patients reached a stable INR
- Out of four studies looking at genotype guided strategy in one arm, three found no difference and the fourth which demonstrated that the genotype guided arm spent more time in-range had a control group with INRs significantly lower than expected
How good is the evidence?
There was a lack of high quality evidence. The overall risk of Any factor, recognised or not, that distorts the findings of a study. For example, reporting bias is a type of bias that occurs when researchers, or others (e.g. drug companies) choose not report or publish the results of a study, or do not provide full information about a study. was found to be A factor that differs among and between groups of people. Examples include people’s age, sex, depression score or smoking habits. , most studies reported adequate Randomization is the process of randomly dividing into groups the people taking part in a trial. One group (the intervention group) will be given the intervention being tested (for example a drug, surgery, or exercise) and compared with a group which does not receive the intervention (the control group). methods but only two studies reported adequate allocation concealment Data is the information collected through research.. Further high quality and adequately The power of a trial is the chance that it will correctly detect a real effect of an intervention being tested (for example a drug, surgery, or exercise). Studies with more participants will have greater power. research needs to be carried out in this area, with adequate follow up and reporting of adverse events.
This review is helpful in showing that when starting warfarin for the first time there is not enough evidence to suggest whether 5mg or 10mg loading doses are safer or quicker. However in older patients smaller doses should be considered.
Mahtani KR, Heneghan CJ, Nunan D, Bankhead C, Keeling D, Ward AM, Harrison SE, Roberts NW, Hobbs FDR, Perera R. Optimal loading dose of warfarin for the initiation of oral anticoagulation. Cochrane Database of Systematic Reviews 2012, Issue 12. Art. No.: CD008685. DOI: 10.1002/14651858.CD008685.pub2.
Harry was with the UK Cochrane Centre from October 2012 – May 2013, where he undertook a fellowship in In systematic reviews we search for and summarize studies that answer a specific research question (e.g. is paracetamol effective and safe for treating back pain?). The studies are identified, assessed, and summarized by using a systematic and predefined approach. They inform recommendations for healthcare and research.. He is currently part way through his Cardiology specialist training within the Oxford Deanery and before this undertook his medical training in London. He is interested evidence based medicine within cardiology, particular in relation to cardiovascular risk in women, imaging and devices.
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