Monitoring DOAC levels not the answer

An increased risk of being rehospitalised for bleeding in people with non-valvular AF taking dabigatran compared to warfarin could be mitigated by monitoring drug plasma levels, researchers suggest.

“Dabigatran works rapidly following its initiation; hence it may lead to more early-onset bleeds,” said Professor Chan, lead investigator on the study and Associate Professor in the department of pharmacology and pharmacy at The University of Hong Kong.

“In contrast, warfarin may take weeks to achieve anticoagulation stability following its initiation, resulting in less bleeding,” she added.

Writing in the paper published in the Journal of Thrombosis and Haemostasis Professor Chan pointed out that the ability to monitor anticoagulation in warfarin likely contributes to the lower rehospitalisation rates and called on drug manufacturers to develop drug monitoring strategies to help improve the safety of the DOAC in this setting.

But speaking to the limbic clinical haematologist Professor Christopher Ward said while he agrees that more work is needed to improve guidance about managing patients on DOACs after a bleed, he’s not convinced that monitoring drug levels are the answer.

“It’s a fair point that because you monitor INR with warfarin you tend to under dose and go up very cautiously after a bleeding admission but as soon as you restart dabigatran you are back at standard level.

But monitoring drugs levels of dabigatran is not helpful – you can’t adjust doses with the DOACs and there’s no proof that giving less is sensible.”

Professor Ward said that rather than a push for drug level monitoring more evidence-based strategies were needed about when to restart oral anticoagulation after a major bleed.

“Going to full anticoagulation after someone has bled can be a tactical error – we need a strategy, we need some kind of evidence, about how to manage people who have bled on a DOAC but need to go back on to it,” he said.

“There are no rules at the moment for this. Personally if I’m asked to see someone who needs anticoagulation after a significant bleed I’ll often temporise with a low dose and often using a low molecular weight heparin and I continue with that until I’m sure the bleed has settled – I don’t use warfarin in that setting.”

He also cautioned that the study findings about warfarin might not be generalisable to Australia because doctors in China tend to use warfarin at much lower doses.

“The comparator is not warfarin at the level we would run people on here – it’s warfarin that is being under dosed as is the convention in China so the comparison is not entirely fair.”

Nevertheless, he said the underlying principle at work is the same:

“If you want consistent anticoagulation then DOACs are clearly better than warfarin but there is a price to pay and that is that there will be a bit more GI bleed and that is a set of bleeds that is likely to recur. That’s clear for all of the DOACs that are active in the gut.”

He said close clinical monitoring of patients during the first 30 days after a bleed, when re-bleed risk is highest, is warranted.

“There is a risk with all of the DOACs that patients may not be followed up routinely so we need to have a mechanism in place to check on people – leaving patients to their own devices during that first month is a mistake.”

The study reported on the hospital records of 51 946 patients with non-valvular AF – 8309 were taking either dabigatran or warfarin while 5160 patients were matched by propensity score.

While the number of people admitted to hospital for a first bleeding event was not significantly different between the two groups investigators said those taking dabigatran had a higher risk of being readmitted to hospital with bleeding – 13.5% compared to 5.1% of warfarin-treated patients.

The results were consistent across both the 110mg and the 150mg doses. The authors also noted that the difference in the risk of readmission between dabigatran and warfarin became statistically non-significant within 60 days of discharge.

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