An editorial report recently published in the Journal of American Medical Association (JAMA) analyzed in depth whether patients with atrial fibrillation (AF), with good international normalized ratio (INR) can benefit from the novel non-vitamin K antagonist oral anticoagulants (NOACs) therapy and concluded that unless more rigorous studies and large clinical trials are designed and conducted, it is difficult to draw a definitive conclusion.

Oral anticoagulation, or blood-thinning, is a medical requirement in patients with atrial fibrillation (or, irregular heartbeat). The AF increases the risk of blood clotting and stroke in such patients. Over years, warfarin, one of the most popular and effective anticoagulants, has been successfully used in patients with AF. Warfarin not only reduces the risk of stroke and blood clotting called thromboembolism, but also increases the rate of survival among such patients. However, warfarin is a complex drug and shows many food and drug interactions. Additionally, patients on warfarin require a strict monitoring of the INR. An INR is a test that is used to monitor individuals being treated with blood-thinners. Warfarin is used in the doses of 2-5 mg initially for the prevention of thromboembolism. The dose is then adjusted according to the result of the INR. However, warfarin is a potent drug and tremendously increases the risk of profuse bleeding and intracranial hemorrhage.

Which Is A Better Anticoagulant In AF: Warfarin Vs Non Vitamin-k

Because warfarin management is difficult, researchers are constantly trying to design, manufacture and market better therapeutic alternatives. Non-vitamin K antagonist oral anticoagulants (NOACs) are one such alternative that have provided a documented benefit in patients with AF. Four recently developed NOACs i.e., Dabigatran (110mg,150 mg), Rivaroxaban (15mg, 20mg), Apixaban (5mg), and Edoxaban (30mg, 60mg) have shown equal efficacy in preventing the risk of stroke in patients with AF.

But are the NOACs really a better choice in patients with AF that is well-managed with warfarin?

Björck and colleagues published an observational analysis of a retrospective study in the latest issue of JAMA Cardiology. The report analyzed several clinical and administrative data sets from Sweden. Sweden boasts the best management of patients with AF in the world in terms of INR control. In their analysis, Björck and co investigated the safety and efficacy of well-managed warfarin in patients with AF and observed a low death rate, and intracranial hemorrhage. Based on the findings, they concluded that a well-managed warfarin is the recommended therapy for patients with AF for stroke prophylaxis.

However, the JAMA editorial questions whether patients that benefited from the warfarin therapy were informed of the alternate anticoagulation therapy available.

Besides, a pertinent question arises in mind that while the study was conducted in Sweden that has the best INR control in the world, how and whether it would apply to patients outside of Sweden.

Furthermore, there is evidence that compared to warfarin, NOAC therapy offers more benefit in AF patients with renal dysfunction in terms of major bleeding, stroke and death.

The JAMA editorial continues that the currently practiced analyses are not designed in a way that can provide sufficient information on patient prognosis as well as treatment decisions regarding anticoagulation therapy. If patients with a good INR control respond well to warfarin treatment, they may as well respond equally good to a NOAC therapy.

The biggest drawback, JAMA editorial thinks, is the lack of a NOAC comparator group. Additionally, Björck and co analyzed the outcomes in the retrospective cohort with well-managed warfarin. Such an analysis cannot provide sufficient information on the prognosis and treatment decisions that are made without knowledge of future. Hence, the observational analysis cannot be used to guide future treatment decisions in warfarin-naïve patients. Also, since the results of the analysis were consistent with the expectations i.e., good INR control in patients, the data of the findings can easily be inappropriately extrapolated.

Rather than banking on the findings of the analysis, the JAMA editorial suggests that future analyses on this topic should carefully sort out and align the interests with the analysis. The traditional risk factors i.e., heart failure, hypertension, aging, diabetes, stroke etc should be carefully evaluated.

While a number of randomized comparisons of warfarin with a NOAC have been conducted, JAMA concludes a new landmark should be established. Questions should be asked whether the patients who will benefit from warfarin or NOAC therapy, can be identified.

Finally, and most importantly, the JAMA editorial concludes, that a definitive answer of warfarin vs NOAC in patients with good INR control would come from conducting a large randomized clinical trial that would include patients with good INR control taking warfarin, who are subsequently randomized to either NOAC or warfarin therapy. For good outcomes, such a trial better be large, randomized and blind. And until such a trial can be arranged, the JAMA editorial suggests conducting rigorously designed and carefully evaluated studies and simple randomized trials.