Apixaban (Eliquis) is Better Tolerated Than Rivaroxaban (Xarelto)
Based on the most recent and highest quality evidence, apixaban demonstrates superior tolerability compared to rivaroxaban, with significantly lower discontinuation rates and reduced bleeding complications.
Discontinuation Rates and Tolerability
Apixaban has consistently demonstrated better tolerability with lower rates of treatment discontinuation across multiple trials:
In the ARISTOTLE trial, apixaban showed fewer early discontinuations compared to warfarin (25.3% vs. 27.5%), indicating good tolerability 1.
In the AVERROES trial, apixaban was significantly better tolerated than aspirin, with permanent discontinuation rates of 17.9% per year versus 20.5% per year for aspirin at 2 years (P = 0.03) 1.
Rivaroxaban, by contrast, had higher premature discontinuation rates than warfarin in the ROCKET-AF trial (23.9% vs. 22.4%), suggesting poorer tolerability 1.
Bleeding Risk Profile
The bleeding profile strongly favors apixaban, which directly impacts tolerability and patient continuation of therapy:
A 2021 large-scale Medicare study of 581,451 patients found rivaroxaban was associated with significantly increased risk of nonfatal extracranial bleeding compared to apixaban (39.7 vs. 18.5 per 1000 person-years; HR 2.07,95% CI 1.99-2.15) 2.
Rivaroxaban showed increased fatal extracranial bleeding compared to apixaban (1.4 vs. 1.0 per 1000 person-years; HR 1.41,95% CI 1.18-1.70) 2.
The same study demonstrated rivaroxaban had higher rates of major hemorrhagic events (7.5 vs. 5.9 per 1000 person-years; RD 1.6, HR 1.26) 2.
Real-world observational data showed rivaroxaban had significantly higher major bleeding risk compared to dabigatran (HR 1.38,95% CI 1.27-1.49), while apixaban demonstrated lower major bleeding rates overall 1.
Gastrointestinal Tolerability
Gastrointestinal side effects represent a major tolerability concern that differentiates these agents:
Rivaroxaban was associated with increased gastrointestinal bleeding and bleeds requiring transfusion in the ROCKET-AF trial 1.
Multiple guidelines note rivaroxaban's association with higher gastrointestinal bleeding rates, particularly in elderly patients 1.
Apixaban showed similar gastrointestinal bleeding rates to warfarin in the ARISTOTLE trial, without the excess seen with rivaroxaban 1.
Clinical Outcomes Affecting Tolerability
The most recent head-to-head comparison provides definitive evidence:
The 2021 Medicare study found rivaroxaban was associated with increased total mortality compared to apixaban (44.2 vs. 41.0 per 1000 person-years; HR 1.06,95% CI 1.02-1.09) 2.
This mortality difference persisted across both standard and reduced dose regimens 2.
The composite primary outcome of major ischemic or hemorrhagic events was significantly higher with rivaroxaban (16.1 vs. 13.4 per 1000 person-years; HR 1.18,95% CI 1.12-1.24) 2.
Common Pitfalls to Avoid
When selecting between these agents, avoid these errors:
Do not assume equivalent tolerability based on both being factor Xa inhibitors—the clinical data clearly differentiate them 2.
Do not overlook the substantially higher extracranial bleeding risk with rivaroxaban, which is the most common reason for discontinuation 2.
Remember that rivaroxaban's once-daily dosing advantage is offset by its poorer safety and tolerability profile 1, 2.
Be particularly cautious with rivaroxaban in elderly patients and those with reduced renal function, where bleeding risk is amplified 1, 2.