Don’t chuck out the rat poison just yet

My grandfather used to joke about his 6 pm dose of rat poison. As a farmer warfarin was something he was accustomed to using to get rid of the rats, so he was always mildly amused that this drug, whilst fatal for rats, was potentially life saving for him for stroke prevention. And for many years warfarin was our only option for treating AF and venous thromboembolism (VTE). A very effective drug, but it was problematic. Regular blood tests needed, a whole host of drug interactions and that nagging doubt that although the benefits outweighed the risks for most people, intra-cranial bleeds were still a very serious potential side effect. 

The concerns over warfarin have resulted in many people with AF not having this potentially stroke and life saving treatment. Was this compounded by a generation of people who were still a bit reluctant to take the drug given it’s association as a rat poison? Who knows. But what we do know is that everything changed with the introduction of the DOACs. With fewer drug interactions, less (but by no means no) blood monitoring, a better safety profile than warfarin, and fixed dosing these have become a huge advance for the treatment of both AF and VTE. All of this has been hugely positive and has led to a significant increase in the percentage of people receiving appropriate anticoagulation for AF. The push to move from warfarin to DOACs was accelerated during the COVID pandemic, to reduce blood tests and footfall through our surgeries.

But, there is always a but. There are some crucial times where DOACs should not be used, in particular people with mechanical heart valves. This was highlighted in a National Patient Safety Alert in July which reviewed a number of cases where people with mechanical heart valves were erroneously switched from warfarin to a DOAC, resulting in significant harm to a few. So we thought it would be a good time to quickly remind us all on the situations where warfarin should generally be used instead of a DOAC, although I’m sure all of us would seek advice from our haematology (or cardiology) colleagues to help guide us in these situations:

1. Mechanical heart valves. The NPSA has highlighted these patients need to remain on warfarin (in the majority of cases) due to the risks of valve thrombosis - if not already done, do make sure your practice has audited all patients with mechanical heart valves to make sure they are receiving the correct anticoagulation. 
2. Moderate/severe mitral stenosis. A small number of patients, but they may develop AF - warfarin may be the preferred anticoagulation. 
3. Anti-phospholipid syndrome. A Drug safety update in June 2019 highlighted the TRAPS study which showed increased thrombotic events in patients taking DOACs vs warfarin. The MHRA recommends warfarin as the preferred option for these people.
4. Severe obesity with weight >120kg. This one may have gone under our radars but was highlighted in the NICE VTE guidance 2020. The guidance highlights the significant lack of data regarding DOAC use in this group and NICE recommend for people >120kg we ‘consider anticoagulation treatment with regular monitoring of therapeutic levels to ensure effective anticoagulation’ (which for most of us means warfarin). Guidance from the International Society on Thrombosis and Haemostasis summaries that although there is no evidence of DOACs being ineffective in this group, there are concerns that with DOACs there is reduced drug exposure, lower peak concentrations and shorter half-lives of the drugs with higher body weights. They recommend that DOACs should not be used for people with weight >120kg or BMI >40.
5. Severe renal failure. All DOACs are contraindicated with estimated creatinine clearance of <15 ml/min and dabigatran is contraindicated with estimated creatinine clearance of <30 ml/min.

So yes DOACs have been a great advance for many reasons, but let’s not chuck away the rat poison just yet - it is still an important and lifesaving drug for some people.