Get the NOAC Knowhow: Novel Oral Anticoagulants Part 1

Where would we be without warfarin?  The good old rat poison has served us brilliantly for decades, allowing us to anticoagulate patients to treat and prevent venous thromboembolism, prevent stroke in AF, and so much more.  As a House Officer, intern or Foundation doc, every doctor must surely have spent hours prescribing warfarin doses and monitoring INRs.  Losing that from our therapeutic armoury would be like Medicine itself losing a limb.

Having said that, warfarin does have its problems.  It takes days and days to work and getting that initial loading dose right for your individual patient can be really hit and miss.  And what about all those drug interactions?  You can’t even prescribe a course of antibiotics without worrying that the patient will end up bleeding out.  For patients, having to come back to Anticoagulant Clinic is really inconvenient.  They have to really watch their diet for vitamin K intake and alcohol is a big no-no.  Despite all that, much of the time their INR won’t even be in the therapeutic range.  Still, it’s cheap and cheerful.

Fortunately we do have an alternative.  Low molecular weight heparin is great.  One injection every day and you’re done.  No monitoring – well, except regular full blood counts and renal profiles, and anti-Factor Xa levels for those with renal impairment.  But having an injection a day isn’t great, either.  Have you seen the abdomens of patients on low molecular weight heparin?  Black and blue isn’t the half of it.

What are the NOACs?

We’ve been talking about these new anticoagulants that will one day replace warfarin for years. I remember one of my patients asking me to prescribe a NOAC at least 5 years ago at a time when they still seemed like science fiction. But the NOACS, or novel oral anticoagulants, have well and truly arrived now and we have the green light to get prescribing. The question is: should we? Are they really the answer to all of our problems or are they merely overpriced products of a corrupt pharma industry; super-anticoagulants that can’t be monitored and that will have our patients bleeding out on a regular basis?

I’m in the very privileged position of being able to ask a particularly knowledgeable friend about all of this. Kerstin de Wit is an emergency physician at McMaster in Canada, who has been doing research into venous thromboembolism for well over a decade and has experience of working at centres of excellence as great as the Ottawa Health Research Institute (with the likes of Ian Stiell and Philip Wells). In a two-part podcast, I asked Kerstin everything you need to know about the NOACS – and we do need to know quite a bit, as these drugs are coming whether we like it or not.

In this first podcast, we go through the basics from what a NOAC is to how it works and when we might consider prescribing one. Here are the key take home messages:

* NOACS work in one of two ways. Drugs like rivaroXAban and apiXAban are factor Xa inhibitors. (The clue is in the name.) Dabigatran works slightly differently, by directly inhibiting thrombin (which converts fibrinogen to fibrin).

* We can use the NOACs for the treatment and/or prophylaxis of deep vein thrombosis and pulmonary embolism, and for the prevention of stroke in atrial fibrillation. There are some other circumstances when we might consider using a NOAC, which we touch on a little more in Part 2, but the best evidence is for these indications.

* There are some important contra-indications to know about. Probably the most important is renal impairment as all of these drugs are renally cleared, at least to some extent. Liver disease is another. Along the same lines, remember that the NOACs will interact with liver enzyme inducers. And we wouldn’t use them in pregnant women (nobody’s sure of the safety) or in patients with cancer (where low molecular weight heparin may be preferable).

* After starting a NOAC, you don’t need to monitor the anticoagulant effect but you do need to periodically check the renal function. You might monitor this more carefully in patients who are at risk of developing renal impairment or who have become unwell. In otherwise well patients an annual check is likely to be enough.

For all the details, check out the podcast. We’ll be back shortly with Part 2, in which we’ll cover the more advanced topics. We hope you enjoy!

Rick and Kerstin

Declarations of interest

Just to make it clear, Kerstin and I have no financial ties to the pharma industry and neither of us have any conflicts of interest to declare. As I mention in the podcast, I am involved in a commercial study sponsored by Boehringer Ingelheim (which manufactures dabigatran) as we’re studying a new reversal agent for dabigatran. However, I certainly don’t have any vested interest in the results and I don’t stand to make any money (or gain any prestige) if the findings are positive. I’m simply a local PI. As such, this is no more a conflict of interest than my involvement in the CRASH-3 or HALT-IT trials are for tranexamic acid!

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