Apixaban vs Rivaroxaban

Both Eliquis and Xarelto have demonstrated superiority or non-inferior ^[1][2]ity to warfarin ^[1][2] in large phase III clinical trials for stroke prevention in atrial fibrillation. The ARISTOTLE trial ^[1] (2011) for apixaban and the ROCKET AF trial ^[2] (2011) for rivaroxaban established their efficacy against warfarin ^[1][2].

In the ARISTOTLE trial ^[1], apixaban 5 mg twice daily reduced the rate of stroke or systemic embolism by 21% compared to warfarin ^[1][2] (1.27% vs 1.60% per year, p<0.01 for superiority). Importantly, apixaban also demonstrated a 31% reduction in major bleeding and an 11% reduction in all-cause mortality compared to warfarin ^[1][2].

In the ROCKET AF trial ^[2], rivaroxaban 20 mg once daily was non-inferior ^[1][2] to warfarin ^[1][2] for stroke prevention (1.7% vs 2.2% per year in the per-protocol analysis). Rivaroxaban did not show a statistically significant reduction in all-cause mortality versus warfarin ^[1][2] in the primary analysis.

A 2019 meta-analysis published in the BMJ comparing DOACs head-to-head using real-world data from over 500,000 patients suggested apixaban may be associated with lower rates of major bleeding compared to rivaroxaban, while maintaining similar stroke prevention efficacy. However, these were observational data and not a direct randomized comparison.

For DVT/PE treatment, both medications have shown efficacy comparable to traditional enoxaparin/warfarin ^[1][2] regimens in the AMPLIFY (apixaban) and EINSTEIN ^[9] (rivaroxaban) trials. Both are also approved for VTE prophylaxis after orthopedic surgery.

Bleeding is the primary safety concern with all anticoagulants. Both Eliquis and Xarelto carry risks of major and minor bleeding events, but their bleeding profiles differ based on clinical trial data.

In the ARISTOTLE trial, apixaban showed significantly lower rates of major bleeding compared to warfarin (2.13% vs 2.42% per year, p=0.03). Rates of intracranial hemorrhage ^[1][2] were also lower with apixaban (0.33% vs 0.80% per year). Gastrointestinal bleeding rates were similar to warfarin.

In the ROCKET AF trial, rivaroxaban had similar overall major bleeding rates to warfarin but showed different patterns: lower intracranial bleeding but higher gastrointestinal bleeding ^[2] rates compared to warfarin. GI bleeding is a notable concern with rivaroxaban, particularly at the 20 mg dose.

Real-world comparative studies consistently suggest apixaban is associated with lower major bleeding rates than rivaroxaban. A large 2022 study using Medicare data found that apixaban was associated with a 30-40% lower risk of GI bleeding compared to rivaroxaban.

Other side effects for both medications include bruising, minor bleeding (nosebleeds, bleeding gums), and rarely, allergic reactions. Neither medication requires routine liver monitoring, though both should be used cautiously in patients with hepatic impairment.

Both Eliquis and Xarelto are brand-name medications with high list prices. Eliquis typically costs $500-$600 per month without insurance, while Xarelto costs approximately ^[4] $500-$550 per month. As of early 2025, generic versions of rivaroxaban have become available, potentially reducing costs to $30-$100 per month depending on the pharmacy.

Generic apixaban is expected to become available in late 2026 when patent exclusivity expires. Until then, Eliquis remains substantially more expensive than generic Xarelto for patients paying out-of-pocket.

Both medications are covered by most insurance plans, though tier placement and copays vary. Manufacturer copay cards are available for both, potentially reducing out-of-pocket costs for commercially insured patients. Patient assistance programs exist for uninsured or underinsured patients.

Dosing convenience is a notable difference between these two medications. Xarelto is taken once daily (20 mg with the evening meal for AF; dosing varies by indication), while Eliquis is taken twice daily (5 mg twice daily for AF; reduced to 2.5 mg twice daily for certain patients).

Xarelto must be taken with food for adequate absorption of the 15 mg and 20 mg doses. Eliquis can be taken with or without food. For patients who struggle with twice-daily medication adherence, Xarelto's once-daily dosing may be advantageous.

Neither medication requires routine blood monitoring (INR testing), which is a significant convenience advantage over warfarin. However, there is no widely available routine test to measure the anticoagulant effect of either drug, which can be a limitation in emergency situations.

The choice between Eliquis and Xarelto should be individualized based on clinical factors, convenience preferences, and cost considerations. Eliquis may be preferred for patients at higher risk of GI bleeding, given its more favorable bleeding profile in clinical trials and real-world studies. Its twice-daily dosing provides more consistent drug levels throughout the day.

Xarelto may be preferred for patients who benefit from once-daily dosing for better adherence, or for those who want to take advantage of generic pricing. It is also the only DOAC approved for use in patients with acute coronary syndrome in combination with antiplatelet therapy.

Patients with significant renal impairment need careful dose adjustment with either drug. Apixaban is less dependent on renal clearance (27% vs 36% for rivaroxaban), which may make it preferable in patients with moderate kidney disease.

Regardless of which medication you take, it is critical never to skip doses or stop taking your blood thinner without medical guidance, as this can significantly increase the risk of stroke or blood clots. Always discuss any concerns with your prescribing provider.