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ENGAGE-AF TIMI 48: Paroxysmal AF associated with lower stroke risk than other AF subtypes
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SAN FRANCISCO — New data from the ENGAGE-AF TIMI 48 trial suggest that patients in the study with paroxysmal atrial fibrillation had a lower risk for most types of stroke, but a similar risk for major bleeding compared with patients in the study with other types of AF.
Results of the subanalysis, which compared edoxaban (Daiichi Sankyo) vs. warfarin for the prevention of stroke or systemic embolic events in patients with nonvalvular AF, were presented at the Heart Rhythm Society Annual Scientific Sessions.
For the subanalysis, researchers categorized on the basis of ECG at randomization the 21,105 patients enrolled in the study by type of AF: paroxysmal, persistent or permanent. All patients had had AF within 12 months of baseline and a CHADS2 score of ≥2. Median follow-up was 2.8 years, making this the longest and largest pivotal trial of a novel oral anticoagulant to date, according to Robert P. Giugliano, MD, SM, researcher and physician at Brigham and Women’s Hospital.
Robert P. Giugliano
Giugliano and colleagues compared results by AF subtype, including the primary efficacy endpoint of stroke or systemic embolic event, the primary safety endpoint of major bleeding and key secondary endpoints. They also evaluated the safety and efficacy of edoxaban vs. warfarin across AF subtypes.
Paroxysmal AF less risky
Compared with patients with other types of AF, those with paroxysmal AF were more likely to be women, have fewer risk factors for stroke, and be prescribed concomitant aspirin and amiodarone.
Rates of stroke/systemic embolic event (adjusted HR=0.77; 95% CI, 0.66-0.91), ischemic stroke, CV death and all-cause mortality were lower in patients with paroxysmal AF compared with patients with permanent AF. However, there was no difference among AF subtypes in rates of hemorrhagic stroke, the researchers found.
Stroke/systemic embolic event rates were 1.5% per year for patients with paroxysmal AF, 1.8% per year for those with persistent AF and 1.9% per year for those with permanent AF, Giugliano said. For the secondary outcome of stroke/systemic embolic event/CV death, rates were 3.2% per year for those with paroxysmal AF, 4.6% per year for those with persistent AF and 4.5% per year for those with permanent AF, he said. The adjusted HR for patients with paroxysmal AF compared with permanent AF was 0.77 (95% CI, 0.7-0.86).
Rates of major bleeding were similar across all AF subtypes (HR=1.04; P=.52). However, patients with paroxysmal AF were more likely to have clinically relevant nonmajor bleeding (HR=1.17; P=.001) and any bleeding (HR=1.19; P<.001) compared with other subtypes of AF, Giugliano said.
Consistent response to edoxaban
In other results, the researchers found no differences by AF subtype in the safety and efficacy of edoxaban compared with warfarin (median time in therapeutic range, 68.4%), according to Giugliano.
“Across AF subtypes, edoxaban compared with well-managed warfarin maintained efficacy to prevent stroke or systemic embolic event, reduced bleeding, reduced CV death and offered a more favorable net outcome,” he said.
While the study results indicate that patients with paroxysmal AF may be at lower risk than patients with other types of AF, their risk should not be minimized, Giugliano said.
“The risk of stroke is still substantial, up to 5%, in patients with paroxysmal AF if they’re not treated,” he said. “We should be anticoagulating patients with paroxysmal AF who have one or more risk factors for stroke.” – by Erik Swain
For more information:
Giugliano RP. Abstract LB02-04. Presented at: Heart Rhythm Society Annual Scientific Sessions; May 7-10, 2014; San Francisco.
Disclosure: The study was funded by Daiichi Sankyo. Giugliano reports financial ties with Bristol-Myers Squibb, Daiichi Sankyo, Janssen Pharmaceuticals and Pfizer.
Perspective
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Andrea M. Russo, MD, FACC, FHRS
A lot of physicians underestimate the risk for thromboembolic complications in patients who have atrial fibrillation. This study evaluated over 21,000 patients with AF. While patients with paroxysmal AF were at lower risk for stroke than patients with other forms of AF, they had fewer risk factors and still had a real risk for stroke. We should still anticoagulate patients who have paroxysmal, persistent or permanent AF if they have risk factors for stroke. I hope people don't interpret the findings as not needing to anticoagulate certain subgroups. It will be interesting to see if there is more information related to the duration of AF and stroke risk in this study.
It's an important trial with a huge number of patients. It gives us more information about the different types of AF, not available in prior studies, as well information about a new anticoagulant medication. All of these novel oral anticoagulants have really changed our practices, and this latest information reinforces our need to pay attention to CHA2DS2-VASc scores and risk factors for thromboembolic complications in the setting of AF.
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