Many of us will have heard about alternatives to warfarin in recent years. There are now 4 of these drugs available (apixaban, dabigatran, edoxaban, rivaroxaban). They used to be called NOACs (novel oral anticoagulants) and now in the medical world are called DOACs (direct oral anticoagulants – they are no longer novel or new!). So what should you know about these drugs?

Anticoagulants are drugs that inhibit the ability of blood to clot. Lay people call them blood thinners, but actually the blood is no thicker or thinner than usual, it just clots less easily as clotting proteins are inhibited. They are used in diseases associated with blood clots, or conditions at risk of clots for example clots in veins/lungs, (venous thromboembolism or VTE), metal heart valves and atrial fibrillation (AF). The latter is an abnormal heart associated with risk of strokes, and anticoagulants strongly reduce this risk by 60-70%.

The drawback of anticoagulants is, not surprisingly, that the reduction of clotting comes with a risk of bleeding. Bleeding can be superficial (bruising, nose bleeds, bleeding from cuts), which troubles patients but medically is not usually dangerous, and internal bleeding which can be very dangerous and even fatal. Despite these risks, for most people, the benefits of anticoagulants in the above conditions is greater than the risk.

The original anticoagulant is warfarin, which has been used in medicine since the 1950s, but drug companies have been searching for alternatives to warfarin for years, because it has a number of drawbacks including the need for careful dosing and regular blood tests, and interactions with other drugs and diet. The DOACs are the first successful tablet alternative to warfarin and they are BIG news.

They were first studied in venous thromboembolism, either treating patients who had clots in veins or at risk of them, for example after joint replacements, and they were very effective. For treating VTE, they have largely taken over from warfarin now. Some of them have been studied in metal heart valves, and the DOAC used there was worse than warfarin, which remains a required treatment in patients with metal valves.

Atrial fibrillation has been an area of intense focus more recently, as it is a common abnormal rhythm, affecting over a million people in the UK, and is responsible for many strokes – 12000 in the UK. As stroke is such a devastating condition, the ability to reduce it has enormous long term benefits. All the DOACs have therefore been keen to show they are as effective as warfarin in protecting against stroke in AF, and all the trials have been positive. All the drugs are at least as effective as warfarin in reducing stroke; they all cause bleeding but in some of the trials DOACs cause less bleeding than warfarin, and in all of them the rare, but serious, chance of bleeding in the brain is marked reduced.

So is warfarin obsolete? Definitely not, in the sense that many patients can still only be treated with warfarin (metal heart valves, clots within the heart pumping chambers (LV thrombus) and DOACs cannot be used in advanced kidney failure). But for atrial fibrillation, if you need an anticoagulant, you are likely to be increasingly offered a DOAC in place of warfarin.
Two other caveats for those really interested in the detail: in some of the trials the benefits of DOACs over warfarin was largely in patients whose warfarin control was less the ideal so if your warfarin control is very good, a DOAC does not give you much advantage; the licensed indications of the DOACs do not cover patients at the lower risk of stroke in AF, and doctors are meant to follow prescribing licenses (they do not always!). Finally, one advantage of warfarin is that doctors know if patients take it as the effect is measured; there is a concern that for patients who are poor at taking their medications, DOACs may be a bad option as we won’t know about it in the way we do with warfarin.

If you would like to read more, here is a recent article in the BMJ:

http://dx.doi.org/
Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis