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Pr John Camm: Atrial fibrillation and triple antithrombotic therapy

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Pr. John Camm : Atrial fibrillation and triple antithrombotic therapy  

MD-FM INSIGHT Tuesday 29 October 2013


 
   

SARAH:

MDFM Medical news from around the world, with Peter Goodwin:


PETER:

Hello. And welcome to our latest expert interview in this Insight edition of MDFM.  With me is Sarah Maxwell.


SARAH:

In cardiology, patient survival has been greatly extended over just a few decades.  Antithrombotic therapy is one important factor in this and the European Society of Cardiology’s 2013 congress in Amsterdam heard opinion from leading experts on some of the latest developments.


PETER

That’s right and there was a debate under the title “Triple antithrombotic therapy: too much of a good thing.” Three-drug-combinations with an oral anti-coagulant (traditionally warfarin) plus aspirin and a second antiplatelet agent, such as clopidogrel, could bring risks, notably bleeding.


SARAH:

Right and who did you hear from at the session?


PETER

Well, firstly, Pr. Harvey White, from New Zealand, and Rikke Sørensen, from Denmark, looked at whether triple therapy could be too much. Then, the debate moved on to ask whether, with all the new anti-platelet agents around, you could do without aspiring altogether. Dr Ten Berg, from the Netherlands, and Pr. Robert Storey, from England, had opposite views on this.  So, afterwards, I turned to co-chair of the debate, Pr. John Camm, of St Georges University of London, for a summary. Could he first, though, run me through the new drugs that could potentially make a difference, starting with the oral anticoagulants?


CAMM:

“We have quite a few: three already approved novel oral anticoagulants that can be used in patients with atrial fibrillation. They all have indications for atrial fibrillation thromboprophylaxis. We also, of course, have other antiplatelet agents, the PY-12 agents, for example there’s prasugrel in addition to ticagrelor and cangrelor and so on and so forth. So there are many potential choices.”


PETER:

Right… Now the impression I get is that things like warfarin are going out, and even clopidogrel is now looking a bit old-fashioned…


CAMM:

“Certainly warfarin is perhaps going out because the novel oral anticoagulants (apixaban, rivaroxaban and dabigatran) are all more effective or as effective as warfarin but with fewer complications, such as intracranial haemorrhage. So the net clinical benefit in treating atrial fibrillation is better with these agents.”


PETER:

Now could you summarize the sorts of points that Dr. White was making: the oral anticoagulants + dual antiplatelet therapy is effective, he said. What were his points mainly?


CAMM:

“Dr. White, in his argument, was concentrating on the efficacy of triple therapy in coping with, on the one hand: stroke risk with atrial fibrillation, on the other hand: stent thrombosis risk, using antiplatelet agents. Thirdly the bleeding risk which, of course, is going to be increased when you use multiple anti-thrombotic agents. And his main point was that the combined therapies are efficacious but you have to be very careful to use them as safely as possible.”


PETER:

And Dr. Sørensen, of course, took issue at so of that…


CAMM:

“Dr. Sørensen’s view was that there was some evidence that alternative approaches could be used as effectively as the triple therapy that we have been discussing, and she also felt that bleeding was a very significant risk and difficult to manage.”


PETER:

Then the debate moved on to “drop the aspirin”. That sounds quite controversial…


CAMM:

“Well, of course, aspirin has been used for a long time… Ever since the ISIS studies they are more or less compulsory therapy (certainly during the acute stages of myocardial infarction) and has generally being continued thereafter, as a measure to reduce the likelihood of recurrent acute coronary syndrome and so forth. But, of course, in those days, aspirin was the only therapy that was being used for this purpose. Nowadays, we have stents in place, patients who have undergone PCI, and they may have other indications for anticoagulant drugs. That’s, of course, where the situation changes.”


PETER:

And what evidence did Dr. Ten Berg give for dropping the aspirin?


CAMM:

“Dr. Ten Berg has conducted a study, which is called the WOEST study and, in that study, he compared patients who needed both forms of therapy. About 70 percent of the patients had atrial fibrillation and most of the patients had PCI and stent placement. And he compared two regimens: one was so-called triple therapy warfarin, clopidogrel and aspirin, and the other group in the trial didn’t take aspirin but did take warfarin and clopidogrel.”


PETER:

However Dr. Storey didn’t agree that that is ok to drop the aspirin…


CAMM:

“Well Dr. Ten Berg showed, in his relatively small study, that there was less bleeding and I think everybody would have expected that in the group that were only taking clopidogrel and warfarin and did not have aspirin. But Dr. Storey pointed out that the trial was a little small to come to any conclusions about the endpoints, such as stent thrombosis and stroke. And, therefore, he thinks that the situation is by no means clear for the time being.”


PETER:

Now you are a doctor in the real world, dealing with all of these factors, weighing them up… What’s your conclusion from all of this, about these patients who are seriously ill, perhaps with atrial fibrillation and having an acute coronary syndrome?


CAMM:

“My conclusion, for the time being at least, is that we should stick with triple therapy and, like Dr. White, I think what we should be doing is making sure that the anticoagulants are well controlled: keeping the INR in the lower half of the effective range, 2 to 2.5, making sure that the patient does not have increased blood pressure, bringing the blood pressure down to absolutely normotensive levels, using PPIs, for example, to diminish the likelihood of gastric irritation and gastrointestinal bleeding. This kind of more holistic approach to the management of the patient may allow triple therapy to be used much more safely.”


PETER:

And triple therapy with what, ideally, typically?


CAMM:

“Well, for the time being, all we have good data in (and it’s not very much) is the combination of warfarin, clopidogrel and aspirin.”


PETER:

But we can indeed do better than that, you think?


CAMM

“At the present time, there are trials involving other agents in triple and double therapeutic regimens. And we are also obtaining a lot of information from registries… And it’s all looking good for the novel oral anticoagulants. And there is very little data on the new antiplatelet agents, and we’re not really secure about whether they will be any better than clopidogrel, but they are theoretical reasons why they should be.”


PETER:

And indeed you’ve been keeping a weather-ear open here at the ESC 2013 conference on NOAC and novel anticoagulants. What’s your summary of what’s come up here?


CAMM:

“Well there have been a number of reports on the NOACs and mostly dealing with trials or subgroups in the large anticoagulant trials with NOACs versus warfarin. There was one very interesting trial called RE-ALIGN, where dabigatran was compared with warfarin, in patients who have had mechanical valves implanted. And, in this study, it was clear that warfarin was superior to dabigatran. And therefore patients, for the time being certainly, with mechanical valves, should continue to be treated with warfarin or another vitamin-K-antagonist and not with a novel anticoagulants.”


PETER:

But the NOACs do have a future ahead of them?


CAMM:

“The NOACs certainly have a very rosy future because they are superior to warfarin in patients with atrial fibrillation, with is nonvalvular in nature.”


PETER:

Professor John Camm of St George’s University of London talking to me at the 2013 congress of the European Society of Cardiology held in Amsterdam.  That’s all from this edition of MDFM.  Sarah Maxwell and I will be back with more very soon.

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