NOACs as Effective as Warfarin for Reducing Stroke, but Apixaban and Dabigatran May Carry Lower Bleeding Risk: Registry

ROME, Italy—A large, nationwide cohort study testing the safety and effectiveness of several novel oral anticoagulants (NOACs) in patients with atrial fibrillation suggests the drugs are as effective as warfarin at reducing the 1-year risk of stroke and are also associated with less bleeding. 

Presenting the results this week at the European Society of Cardiology Congress 2016 in Rome, Italy, lead investigator Laila Staerk, MD (Herlev and Gentofte University Hospital, Denmark) reported that dabigatran (Pradaxa, Boehringer Ingelheim) and apixaban (Eliquis, Pfizer/Bristol-Myers Squibb) were associated with a small but statistically significant decrease in the risk of intracranial bleeding compared with warfarin. Overall, the absolute reduction in the risk of intracranial hemorrhage with dabigatran and apixaban was 0.34% and 0.20%, respectively, when compared with the vitamin K antagonist.    

There was a trend toward a lower risk of bleeding with rivaroxaban (Xarelto, Bayer Pharma/Janssen Pharmaceuticals)—an absolute reduction of 0.13%-—compared with warfarin, but the difference was not statistically significant.  

Speaking during a press conference, Staerk said the four anticoagulant treatments are currently available in Denmark but noted that their use remains a “double-edged sword.” While atrial fibrillation is associated with an approximately five-fold greater risk of stroke, anticoagulation to reduce the risk can cause bleeding, including severe intracranial bleeding. 

Given this, the researchers assessed the risk of stroke and intracranial hemorrhage among 43,299 A-fib patients in Denmark who started oral anticoagulation: 41.8% were treated with warfarin, 29.1% with dabigatran, 13.2% with rivaroxaban, and 15.9% with apixaban. 

At 1 year, the absolute risk of stroke ranged from 2.01% to 2.46% among the drugs, although there was no statistically significant difference between the warfarin- and NOAC-treated patients. Staerk said treatment with any of the agents prevented stroke in approximately 20 to 25 patients for every 1,000 who received oral anticoagulation. 

The absolute risk of intracranial bleeding with dabigatran, apixaban, rivaroxaban, and warfarin was 0.26%, 0.40%, 0.47%, and 0.60%, respectively. For every 1,000 patients treated with warfarin, there would be approximately six intracranial bleeds compared with three intracranial bleeds with dabigatran and four bleeding events with apixaban.

Speaking during the press conference, Staerk said they adjusted for patient variables, including baseline comorbidities and risk factors incorporated into the CHA₂DS₂-VASC and HAS-BLED scores. She said the data are particularly relevant given that it is an unselected patient population. “[The registry] also includes patients at high risk for bleeding, some of whom were excluded from the randomized clinical trials,” said Staerk.  

Gerhard Hindricks, MD, PhD (Leipzig University Heart Center, Germany), who chaired the press conference where the results were presented, said the data reinforce what was previously observed in the large-scale clinical trials testing the newer anticoagulants against warfarin. Those studies included RE-LY with dabigatran, ROCKET-AF with rivaroxaban, and ARISTOTLE with apixaban. 

“The clinical trials are prospective studies with very defined populations,” said Hindricks. “Here, we have the strength of the entire nationwide population, and what it shows is that the NOACs are indeed noninferior to warfarin, which was the primary hypothesis of all the trials, and they are safer.” As for preferences of one agent over another, Hindricks doesn’t believe there is a large difference between the different drugs, saying he “thinks they’re all good.” 

ESC spokesperson Christian Gerdes, MD (Aarhus University Hospital, Denmark), said the registry studies are important as they “provide insight into what happens in real life.” The study suggests that in the real-world setting, the NOACs are safe to use—maybe even a bit safer than warfarin—and “that we can actually handle these new drugs, which is reassuring,” he concluded. 

Source:

• Staerk L. Ischemic and hemorrhagic stroke associated with NOACs and warfarin use in patients with atrial fibrillation: a nationwide cohort study. Presented at: European Society of Cardiology Congress 2016. August 27, 2016. Rome, Italy.

Disclosures:

• Staerk reports receiving a restricted research grant from Boehringer-Ingelheim outside the presented data.

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