No Benefit and More Bleeds With Antiplatelet for AF Patients With Stable CAD

January 31, 2014

LONDON, UK – Data from a large cohort study confirm the heightened risk of serious bleeding in atrial fibrillation (AF) patients with stable coronary artery disease treated with a vitamin-K antagonist and antiplatelet medication, such as aspirin or clopidogrel[1].

Despite adding the antiplatelet to the anticoagulant, there was no significant reduction in the risk of MI or coronary death when compared with those who received anticoagulation alone, yet there was a significantly increased risk of serious bleeding.

"There is the perception that if patients have concomitant vascular disease, whether it's coronary or peripheral artery disease, they will need antiplatelet therapy despite being on oral anticoagulant therapy," Dr Gregory Lip (University of Birmingham, UK) told heartwire . "This is despite all the guidelines and the evidence that says if you add an antiplatelet on top of anticoagulant therapy you don't really make any impact on stroke, myocardial infarction, or mortality. What you really do is substantially increase the risk of major or intracranial bleeding."

Lip, who is a coauthor on the paper, which is published online January 28, 2014 in Circulation, pointed out that the European Society of Cardiology (ESC) Working Group on Thrombosis/Task Force on Anticoagulants in Heart Disease state explicitly that antiplatelet therapy should not be added to an anticoagulant in patients with stable vascular disease and AF, given the increased risk of bleeding (IA recommendation). Only in patients who refuse warfarin or the new oral anticoagulants for the prevention of stroke should aspirin/clopidogrel combination therapy or the less effective aspirin alone be considered (IIb-B recommendation).

For those who undergo PCI, the US and European guidelines recommend adding aspirin and clopidogrel for as long as one month to one year after an acute coronary syndrome (ACS). However, as the authors note in their paper, oral anticoagulation is not recommended in patients who had the ACS or revascularization procedure more than 12 months earlier.

Still, despite these guidelines, physicians are keeping patients on antiplatelet medications in addition to oral anticoagulation after AF patients with coronary artery disease have stabilized, said Lip.

In their new report, the researchers, led by Dr Morten Lamberts (Copenhagen University Hospital, Denmark), identified 8700 AF patients with stable coronary disease (defined as 12 months from an acute coronary event) treated between 2002 and 2011. During a mean follow-up of 3.3 years, the risk of MI/coronary death was similar for those treated with warfarin, those who received warfarin plus aspirin, and those treated with warfarin plus aspirin and clopidogrel. The risk of thromboembolic events was also similar in all three treatment groups.

For bleeding, however, those treated with aspirin on top of warfarin had a 50% higher risk and those treated with aspirin and clopidogrel on top of warfarin had an 84% higher risk. "The only significant p values in this particular paper, as well as in other analyses, are for the increase in major bleeding and for the increase in intracranial hemorrhage," Lip told heartwire .

Real-World Antithrombotic Use in AF

In addition to the paper on the risks of the combination therapy in AF patients with coronary disease, Lip is the first author of a new report highlighting the real-world use of antithrombotic treatment in patients with AF[2]. The report, published online January 30, 2014 in the American Journal of Medicine, is an analysis of the pilot survey of the Euro-Observational Research Program on Atrial Fibrillation and includes 3119 patients.

Lip noted that a EuroHeart survey was published in 2006 and found that antithrombotic therapy was often disconnected to the patient's stroke risk and that other factors aside from these stroke risk factors often swayed antithrombotic treatment decisions. Since 2006, however, the ESC has published clinical guidelines (2010) and a focused update (2012) on the management of patients with AF.

Noting that a lot has changed since 2006, Lip told heartwire that the European cardiologists are not faring too badly. Eight years ago, according to the EuroHeart survey, the rate of anticoagulation was only about 55% or 60%. In the present survey, however, 72.2% of patients were prescribed vitamin-K antagonists.

However, Lip said there are some observations that suggest the treatment of AF is not entirely ideal.

"For example, antiplatelet therapy, largely aspirin, is still commonly used," said Lip. "It is also commonly used in combination with anticoagulation, and that's not a good thing." The survey also showed that AF patients with paroxysmal AF and elderly patients were less likely to receive anticoagulation, he added, noting that these highlight areas where treatment can improve.

The survey also revealed that just 7.7% of patients were prescribed the new oral anticoagulants, such as dabigatran etexilate (Pradaxa, Boehringer Ingelheim), rivaroxaban (Xarelto, Bayer Pharma/Janssen Pharmaceuticals), or apixaban (Eliquis, Bristol-Myers Squibb/Pfizer). Lip notes that some countries require patients to undergo a "warfarin stress test" before being treated with a novel anticoagulant. However, in this early stage it's unlikely they'll achieve an adequate time in therapeutic range, and this leaves them vulnerable as they'll be undercoagulated prior to starting the newer oral anticoagulants.

"We need to get better at identifying the patients who would do well on warfarin and those less likely to do well," he told heartwire . "This way we can just start them up front with a novel anticoagulant."

Lip reports consulting for Bayer, Medtronic, Sanofi, Bristol-Myers Squibb/Pfizer, Daiichi-Sankyo, and Boehringer Ingelheim and having been a speaker for Bayer, Bristol-Myers Squibb/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, and Medtronic. Disclosures for the coauthors are listed in the papers.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.