News Release

PHILADELPHIA—A difference in the effectiveness against strokes and other blood clots was easily visible in the first year among patients who’d taken the anticoagulant apixaban rather than rival rivaroxaban, according to researchers at the Perelman School of Medicine at the University of Pennsylvania.

In the “emulated” clinical trial—an analysis comparing matched patients in a large health insurance database—all of the patients whose data were analyzed were those who have atrial fibrillation (AF) and associated valvular heart disease (VHD). Each patient took one form of an anticoagulant, also known as blood thinners, to slow down the formation of new blood clots and help avoid existing clots from growing larger and potentially more harmful. The study showed that thosewho took apixaban had their dangerous clot risk decrease almost by half compared with rivaroxaban.

At least several million Americans have AF, a type of irregular heartbeat that lead to blood clots in the heart, and it is thought that more than 60 percent of these patients have associated VHD, which essentially means that they also have significant heart valve damage. Stroke or systemic embolism risk increase by several times in those with AF compared to those without it, and VHD is suspected of adding to the risk of stroke or death.

Since 2016, apixaban and rivaroxaban have been the most prescribed anticoagulants for reducing stroke and systemic embolism risk in AF/VHD patients. While some traditional blood thinners can be affected by a patient’s diet, apixaban and rivaroxaban do not, making them easier to manage. But, so far, there have been no clinical trials directly comparing the two drugs in this patient population.

“The lack of clinical trial evidence and wide use of both drugs in patients with AF and VHD calls for real-world evidence that can guide treatment selection in clinical practice,” said Ghadeer Dawwas, PhD, a postdoctoral fellow in Biostatistics, Epidemiology, and Informatics at Penn, and first author of the study, published today in the Annals of Internal Medicine.

Almost 10,000 patients who had recently started taking apixaban were compared with another 10,000 newly taking rivaroxaban. The study was not of the clinical trial type, in which patients are randomly assigned to different groups to minimize differences between them. Rather, the researchers emulated a clinical trial by matching each patient in the apixaban group to one in the rivaroxaban group with similar age and other characteristics that could affect outcomes. The patient records compared in the study came from a large commercial health insurance database with de-identified data from 2013 to 2020.

The number of strokes, as well as blood clots in the body other than the brain (called “systemic embolisms”) in the patients seen over the span of several years after they began taking the medications suggested that patients in the apixaban group had a 43 percent lower risk of a clotting event, and a 49 percent lower risk of a gastrointestinal or intracranial bleeding event.

“Until evidence from randomized controlled trials becomes available, we believe clinicians should consider our findings when selecting anticoagulants in patients with AF and VHD,” said study senior author Sean Hennessy, PharmD, PhD, a professor of Epidemiology and director of Penn’s Center for Real-world Effectiveness and Safety of Therapeutics.

The analysis showed that the numbers of patients who had strokes or systemic emboli in each group diverged almost immediately. Patients in the rivaroxaban group had markedly more of these events at six months and twelve months of follow-up. The researchers calculated that the rate of stroke or systemic embolism per patient per year of follow-up was about one percent (0.91 percent) for rivaroxaban users, and about half that (0.52 percent) for apixaban users. Similarly, the rate of bleeding events in the rivaroxaban group was about double that in the apixaban group.

Overall the results suggested that, in comparison to the rivaroxaban group, the apixaban group had 43 percent lower risk of stroke or systemic embolism, and 49 percent the risk of a bleeding events compared with rivaroxaban.

Support for the research was provided by the National Institutes of Health (K99HL159230).


Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $9.9 billion enterprise.

The Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $546 million awarded in the 2021 fiscal year.

The University of Pennsylvania Health System’s patient care facilities include: the Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center—which are recognized as one of the nation’s top “Honor Roll” hospitals by U.S. News & World Report—Chester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; and Pennsylvania Hospital, the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.

Penn Medicine is powered by a talented and dedicated workforce of more than 47,000 people. The organization also has alliances with top community health systems across both Southeastern Pennsylvania and Southern New Jersey, creating more options for patients no matter where they live.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2021, Penn Medicine provided more than $619 million to benefit our community.

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