Eliquis vs. Xarelto: A Deep Dive into Safety and Efficacy
Eliquis (apixaban) and Xarelto (rivaroxaban) are modern anticoagulants known as direct-acting oral anticoagulants (DOACs). Both work by inhibiting a key clotting protein called Factor Xa, which helps prevent the formation of dangerous blood clots [1.2.2, 1.5.4]. They are commonly prescribed to reduce the risk of stroke in patients with nonvalvular atrial fibrillation (Afib) and to treat or prevent deep vein thrombosis (DVT) and pulmonary embolism (PE) [1.2.1, 1.5.5].
While they share a mechanism of action, their differences in chemical structure, dosing, and how the body processes them lead to distinct safety and effectiveness profiles that are critical for patients and clinicians to understand.
Effectiveness: Preventing Stroke and Blood Clots
When it comes to preventing stroke in patients with Afib, multiple large observational studies and meta-analyses suggest a potential advantage for Eliquis. A significant 2021 study published in JAMA using data from over 580,000 Medicare beneficiaries found that Eliquis (apixaban) was associated with a lower rate of major ischemic events (like stroke) compared to Xarelto (rivaroxaban) [1.2.3, 1.2.8]. Other analyses have echoed this, finding Eliquis to be more effective for this purpose [1.2.4, 1.2.5, 1.2.6]. For treating and preventing DVT and PE, both medications are considered highly effective, though some evidence again suggests a better safety profile for Eliquis [1.3.2].
Safety Profile: The Critical Question of Bleeding Risk
The most significant risk for any anticoagulant is bleeding. This is where the most pronounced differences between Eliquis and Xarelto appear in clinical data.
Major Bleeding: A consistent body of evidence from numerous retrospective and real-world studies indicates that Eliquis is associated with a lower risk of major bleeding events compared to Xarelto [1.2.2, 1.3.3, 1.3.5, 1.3.6]. A 2025 study published in JACC: Advances concluded that among patients with Afib and/or VTE, bleeding rates were highest with rivaroxaban and lowest with apixaban [1.3.5].
Gastrointestinal (GI) Bleeding: The difference is particularly notable regarding GI bleeding. Multiple meta-analyses and large cohort studies have found that Xarelto carries a significantly higher risk of GI bleeding than Eliquis [1.4.1, 1.4.4, 1.4.7, 1.4.8]. Research published in Gastroenterology concluded that apixaban had the most favorable GI safety profile among DOACs [1.4.5].
Considerations for Specific Populations:
- Older Adults: The risk of bleeding with Xarelto increases with age, a concern not observed with Eliquis [1.2.4, 1.2.7]. For this reason, Eliquis is often considered a safer option for many older individuals [1.2.5]. A recent Swedish study on patients 65 and older confirmed that rivaroxaban was associated with a higher risk of major bleeding than apixaban during the first six months of treatment [1.3.1].
- Kidney Disease: Eliquis is less dependent on the kidneys for elimination from the body. Consequently, it is often the preferred agent for patients with moderate to severe kidney problems, as Xarelto may require dose adjustments or be less suitable [1.2.1, 1.2.5, 1.5.6].
Head-to-Head Comparison Table
| Feature | Eliquis (apixaban) | Xarelto (rivaroxaban) |
|---|---|---|
| Mechanism | Direct Factor Xa Inhibitor [1.2.2] | Direct Factor Xa Inhibitor [1.2.2] |
| Typical Dosing | Twice daily (e.g., 5 mg twice a day) [1.5.2] | Once daily (e.g., 20 mg once a day) [1.5.2] |
| Take with Food? | Can be taken with or without food [1.5.3] | Should be taken with food for Afib and VTE treatment [1.5.3] |
| Effectiveness (Afib) | May be more effective in preventing stroke [1.2.3, 1.2.5] | Highly effective, but some studies show fewer events with Eliquis [1.2.6] |
| Major Bleeding Risk | Lower risk compared to Xarelto in multiple studies [1.3.3, 1.3.5] | Higher risk compared to Eliquis in multiple studies [1.3.6, 1.3.8] |
| GI Bleeding Risk | Lower risk; more favorable GI safety profile [1.4.5, 1.4.8] | Higher risk compared to Eliquis [1.4.1, 1.4.7] |
| Use in Older Adults | Bleeding risk not age-related; often preferred [1.2.4, 1.2.5] | Bleeding risk increases with age [1.2.7] |
| Use in Kidney Disease | Often preferred due to lower kidney clearance [1.2.1, 1.2.5] | May require dose adjustments [1.5.3] |
Dosing, Convenience, and Cost
Xarelto's primary advantage for many patients is its once-daily dosing, which can improve adherence [1.5.5]. However, the twice-daily dosing of Eliquis provides more consistent blood levels of the medication throughout the day, which may contribute to its safety profile [1.3.5, 1.5.5]. Both drugs are available as brand-name products, though generic versions of apixaban have recently become available, potentially lowering costs [1.3.7].
Conclusion
Deciding which blood thinner is safer, Eliquis or Xarelto, depends on individual patient factors. However, a large and growing body of real-world evidence suggests that Eliquis (apixaban) has a more favorable safety profile, with a consistently lower risk of both major bleeding and gastrointestinal bleeding compared to Xarelto (rivaroxaban) [1.3.3, 1.3.5, 1.4.8]. This advantage appears to be more pronounced in older adults and patients with impaired kidney function [1.2.5, 1.3.4].
While Xarelto offers the convenience of once-daily dosing, the data on safety and, in some cases, effectiveness, points toward Eliquis as being the preferable agent for many patients with nonvalvular atrial fibrillation. The ultimate decision must be made in consultation with a healthcare provider who can weigh an individual's specific stroke risk, bleeding risk, kidney function, and other medical conditions [1.2.2].
For further reading, see the Vanderbilt University Medical Center's report on the pivotal JAMA study: Study finds apixaban (Eliquis) is preferable to rivaroxaban (Xarelto) for stroke prevention, reduced bleeding complications [1.2.3]
