11th September 2021, Dr Chee L Khoo
You may recall when direct acting oral anti-coagulants (DOAC) first came out for treatment of atrial fibrillation (AF). Upon diagnosis of new AF, some GPs were hesitant to initiate a DOAC for the AF but instead refer patients to a cardiologist. There is a danger while waiting to see the cardiologist that the patient may incur a cerebrovascular accident (CVA). What if you missed that diastolic murmur and started someone on a DOAC for their AF when they have valvular heart disease? I mean, diagnosis of mitral valve disease may not be straight forward. DOACs are not indicated for valvular AF not because of potential harm but more because the data on efficacy on stroke prevention for patients with valvular AF were not available yet. We now have the data.
DOACs directly block the clotting factors. We have those that block factor Xa (apixaban, rivaroxaban, edoxaban) and those that block thrombin (dabigatran). These agents have taken away a lot of uncertainty because they act on one area of the clotting cascade and are much more predictable. Warfarin was the gold standard for stroke prevention in AF but it is a difficult medication to use because of the drug-drug interaction and drug-food interaction. DOACs do not involve Vitamin K, so all dietary issues are gone. And with that the regular INR monitoring.
The original trials that compared these DOACs with warfarin in patients with AF only had patients who had non-valvular atrial fibrillation. Not only were they shown to be as good as warfarin for stroke prevention, in some cases, they were superior to warfarin for stroke prevention. The cream on top is that they all are associated with less major bleeding including intracranial haemorrhage. So, for patients with nonvalvular atrial fibrillation, the DOACs were the preferred choice.
What about patients with valvular AF? In a retrospective propensity score–matched cohort study data from a US commercial health care database were analysed. Data from 56,336 patients with valvular atrial fibrillation who were newly prescribed either a DOAC or warfarin analysed. They assessed the safety and efficacy of DOACs compared with warfarin. The primary effectiveness outcome was a composite of ischaemic stroke or systemic embolism. The primary safety outcome was a composite of intracranial or gastrointestinal bleeding.
Results:
Heart failure was present in 46% to 48% of patients, and the mitral valve was the most common diseased heart valve (~56%). Compared with warfarin, the use of all DOACs combined was associated with 36% lower risk of thromboembolic events and 33% lower risk of major bleeding events. The results for apixaban had 46% reduction in events and 48% reduction in bleeding while rivaroxaban had 26% reduction in events and 13% reduction in bleeding. With dabigatran, there was reduction of major bleeding outcome of 19% but did not reduce thromboembolism risk.
Now, this is not a randomised controlled trial. This is mostly an observational study. Further, there were no mechanical valves in this study, and, for mechanical valves, which are more thrombogenic, we need to continue to use warfarin and make sure we have the patients on a higher anticoagulation level.
But, for patients with all other valvular atrial fibrillation, it would seem that DOAC is better than warfarin in reducing thromboembolic events and reduce risk of bleeding. This is but the first of studies which may see warfarin being replaced by DOAC for management of both valvular as well as non-valvular AF. Oh, it’s not approved by the TGA yet.
References:
Dawwas GK, Dietrich E, Cuker A, Barnes GD, Leonard CE, Lewis JD. Effectiveness and Safety of Direct Oral Anticoagulants Versus Warfarin in Patients With Valvular Atrial Fibrillation : A Population-Based Cohort Study. Ann Intern Med. 2021 Jul;174(7):910-919. doi: 10.7326/M20-6194. Epub 2021 Mar 30. PMID: 33780291.