Oral anticoagulation (OAC) reduces the risk of thromboembolic events in patients with atrial fibrillation (AF); however, thromboembolism (TE) still can occur despite OAC. Factors associated with residual risk for stroke, systemic embolism, or transient ischemic attack events despite OAC have not been well described.
The purpose of this study was to evaluate the residual risk of thromboembolic events in patients with AF despite OAC.
A total of 18,955 patients were analyzed in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF I and II) using multivariable Cox proportional hazard modeling. Mean age was 72 ± 10.7, and 42% were women. There were 451 outcome events.
The risk of TE despite OAC increased with CHA2DS2-VASc score: 0.76 (95% confidence interval [CI] 0.63–0.92) events per 100 patient-years for CHA2DS2-VASc score <4 vs 2.01 (95% CI 1.81–2.24) events per 100-patient years for CHA2DS2-VASc score >4. Factors associated with increased risk were previous stroke or transient ischemic attack (hazard ratio [HR] 2.87; 95% CI 2.30–3.59; P <.001), female sex (HR 1.52; 95% CI 1.24–1.86; P <.001), hypertension (HR 1.50; 95% CI 1.09–2.06; P = .01), and permanent AF (HR 1.47; 95% CI 1.12–1.94; P = .001). When transient ischemic attack was excluded, the results were similar, but permanent AF was no longer significantly associated with thromboembolic events.
Patients with AF have a residual risk of TE with increasing CHA2DS2-VASc score despite OAC. Key risk markers include previous stroke/transient ischemic attack, female sex, hypertension, and permanent AF.
ORBIT AF was funded by a research grant from Janssen Pharmaceuticals. This work was supported by the Duke Clinical Research Institute.
Dr Fudim is supported by American Heart Association Grant 17MCPRP33460225 and NIH T32 Grant 5T32HL007101; and is a consultant for Coridea and Galvani. Dr Fonarow reported receiving personal fees from Janssen, Bayer , Medtronic , Abbott , Novartis , and AstraZeneca . Dr Naccarelli reported receiving grants from Janssen; and receiving personal fees from Janssen, Omeicos, Ascension, Sanofi , Milestone, and GlaxoSmithKline . Dr Gersh reported receiving personal fees from Janssen Scientific Affairs, Boston Scientific , Janssen, BMS, and Sanofi . Dr Reiffel reported receiving grants from Janssen; receiving personal fees from Janssen, Portola, and Boehringer Ingelheim; and working as an investigator and/or consultant regarding antiarrhythmic control of and diagnostic monitoring for atrial fibrillation. Dr Kowey served as an ad hoc for Johnson & Johnson; and reported receiving personal fees from Johnson & Johnson . Dr Steinberg is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number K23HL143156; receives research support from Boston Scientific and Janssen; reports consulting to Janssen, AltaThera, and Merit Medical; and speaking for NACCME (funded by Sanofi ). Dr Freeman reported receiving grant support from NHLBI; salary support from American College of Cardiology; and serving on consulting/advisory boards for Janssen Pharmaceutical, Biosense Webster , Boston Scientific , and Medtronic . Dr Ezekowitz serves as a consultant to Allergan , Abbott , Bayer , Johnson & Johnson , Medtronic , Sanofi, and Phillips; consults for Abbott , Boston Scientific , Janssen Pharmaceuticals , Bayer , Pfizer , BMS, and Boehringer Ingelheim; and has received grants from Pfizer and Boehringer Ingelheim . Dr Singer reported receiving personal fees from Johnson & Johnson , Pfizer , and Merck; and receiving grants and personal fees from Boehringer Ingelheim and Bristol-Myers Squibb . Dr Allen reported contracts with Janssen and Novartis. Dr Chan reported consulting for Optum Rx. Dr Pokorney reported receiving grants from Janssen Pharmaceuticals and the US Food and Drug Administration; receiving grants and personal fees from Bristol-Myers Squibb , Pfizer , Boston Scientific , and Janssen Pharmaceuticals; and receiving personal fees from Medtronic and Philips . Dr Peterson reported receiving grants and personal fees from Janssen, Amgen , AstraZeneca , Merck & Co, and Sanofi . Dr Piccini is supported by R01AG074185 from the National Institutes of Aging; receives grants for clinical research from Abbott , the American Heart Association , the Association for the Advancement of Medical Instrumentation, Bayer , Boston Scientific , iRhythm, and Philips; and serves as a consultant to Abbott , Abbvie , ARCA biopharma, Bayer , Boston Scientific , Bristol-Myers Squibb (Myokardia), Element Science, Itamar Medical, LivaNova , Medtronic , Milestone, ElectroPhysiology Frontiers, ReCor , Sanofi , Philips , and Up-to-Date.
All authors attest they meet the current ICMJE criteria for authorship.
Patients provided written informed consent and were not compensated for their participation.
All participating sites in the ORBIT-AF I and ORBIT-AF II registries obtained institutional review board approval, including Duke Institutional Review Board approval, before patient recruitment. The research reported adhered to relevant ethical guidelines, including the Helsinki Declaration as revised in 2013.
Published online: September 27, 2022
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