Millions of Americans take a blood thinner to reduce the risk of stroke and dangerous blood clots, and the question of Eliquis vs Xarelto comes up in cardiology offices every day. Both belong to the direct oral anticoagulant (DOAC) class that has largely replaced warfarin for many patients, yet they differ in dosing frequency, bleeding-risk data, and cost. Understanding these differences can help you have a more productive conversation with your prescriber. This article is educational only and is not medical advice; every decision about these medicines should be made with your doctor.
How Eliquis and Xarelto Work
Eliquis (apixaban) and Xarelto (rivaroxaban) are both Factor Xa inhibitors. They block a specific protein in the clotting cascade called Factor Xa, which plays a central role in converting prothrombin to thrombin, the enzyme that ultimately helps form blood clots. By targeting this single step, both medications thin the blood predictably enough that the routine blood monitoring required with warfarin is generally unnecessary.
Despite sharing the same mechanism, the two drugs differ in how they are taken. Xarelto is typically taken once daily for many indications, and its larger doses should be taken with food to improve absorption. Eliquis is generally taken twice daily, which can provide more consistent drug levels through the day but requires remembering a second dose. Your prescriber determines your exact dose and schedule based on your diagnosis, kidney function, and other factors, so this article does not list specific milligram amounts. The FDA has approved both drugs for stroke prevention in non-valvular atrial fibrillation, for treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and for reducing the risk of DVT and PE, including after certain hip or knee replacement surgeries.
Boxed Warnings You Should Know
Both Eliquis and Xarelto carry FDA boxed warnings, the agency’s most serious type of warning. Knowing them is essential for using either drug safely.
- Do not stop the medicine abruptly. Stopping either drug early, without your doctor arranging alternative anticoagulation, increases the risk of thrombotic events such as stroke and blood clots. If you must stop for any reason, your prescriber will manage the transition. Never discontinue on your own, even if you feel fine or run out of pills.
- Risk of spinal or epidural blood clots (hematoma). Patients who receive spinal or epidural anesthesia (neuraxial anesthesia) or who undergo a spinal puncture while taking these drugs are at risk of developing a blood clot around the spinal cord that can lead to long-term or permanent paralysis. Tell any anesthesiologist, surgeon, or clinician performing a spinal procedure that you take a blood thinner well in advance.
These warnings are why timing, communication, and never self-adjusting your medication matter so much with any DOAC.
Effectiveness: What the Clinical Trials Show
The landmark trials for these medications, ARISTOTLE for Eliquis and ROCKET AF for Xarelto, both compared their respective drug against warfarin in patients with non-valvular atrial fibrillation. The ARISTOTLE trial found that apixaban was superior to warfarin in preventing stroke and systemic embolism, caused significantly less major bleeding, and was associated with lower all-cause mortality.
The ROCKET AF trial demonstrated that rivaroxaban was non-inferior to warfarin for stroke prevention, meaning it performed at least as well, though it did not achieve statistical superiority. Major bleeding rates were broadly similar between Xarelto and warfarin overall, while Xarelto showed lower rates of intracranial and fatal bleeding in that trial.
Large real-world studies comparing the two DOACs have generally found that apixaban is associated with lower rates of major bleeding, particularly gastrointestinal bleeding, with similar stroke-prevention effectiveness. Because head-to-head randomized trials directly comparing the two are limited, much of this comparison rests on observational data, which many clinicians weigh alongside a patient’s individual risk factors. This accumulating evidence is one reason many clinicians favor Eliquis when bleeding risk is a primary concern, but Xarelto remains a well-established, effective option.
Bleeding Risk and Side Effects
Bleeding is the most significant risk of any anticoagulant, including both of these drugs. When comparing Eliquis vs Xarelto, multiple studies and meta-analyses suggest Eliquis may carry a lower risk of gastrointestinal bleeding, which is particularly relevant for older patients and those with a history of GI issues. That said, both drugs can cause serious and occasionally life-threatening bleeding.
Know the warning signs of serious bleeding. Because bleeding is the main danger of both Eliquis and Xarelto, seek medical care right away if you notice any of the following, and call 911 for severe, heavy, or uncontrolled bleeding:
- Unusual or unexplained bruising, or bruises that keep getting bigger
- Bleeding that will not stop, or that takes much longer than usual to stop
- Pink, red, or brown urine
- Red, black, or tarry stools
- Coughing up or vomiting blood, or vomit that looks like coffee grounds
- A sudden, severe headache, or dizziness, weakness, or confusion (possible signs of bleeding in the brain)
- Nosebleeds or gum bleeding that are heavy or hard to stop
Do not stop your medication on your own even if you notice bleeding; contact your doctor or emergency services for guidance.
Common Side Effects of Eliquis
- Bruising
- Nosebleeds
- Minor bleeding from cuts
- Nausea
- Anemia (with prolonged use)
Common Side Effects of Xarelto
- Bruising
- Bleeding, including gastrointestinal bleeding
- Nosebleeds
- Back pain
- Muscle spasms
- Dizziness
Both drugs have an FDA-approved reversal agent, andexanet alfa (Andexxa), which can be used in hospital settings to help reverse the anticoagulant effect during life-threatening or uncontrolled bleeding. It is expensive and available only in hospitals. It is worth clearing up a common point of confusion: idarucizumab (Praxbind) is a reversal agent for dabigatran (Pradaxa), a different type of blood thinner, and is not used to reverse Eliquis or Xarelto.
Dosing Frequency and Convenience
Xarelto’s once-daily dosing for many indications is often cited as a convenience advantage, particularly for patients who struggle with medication adherence. Missing a dose of any blood thinner can briefly raise clot risk, and having fewer doses to remember can make a practical difference. Xarelto’s larger doses should be taken with food to ensure adequate absorption.
Eliquis is generally taken twice daily. While that schedule is slightly more demanding, spreading the dose across the day means a single missed dose may have less impact on overall drug levels. Your prescriber will tell you exactly how much to take and when, and what to do if you miss a dose; do not create your own schedule or double up without professional guidance.
Neither medication requires the regular INR blood tests or the vitamin-K dietary restrictions that warfarin demands, which is a significant quality-of-life improvement for patients switching from warfarin. For general dietary guidance with these medications, see our articles on foods to avoid when taking Eliquis and foods to avoid when taking Xarelto.
Cost Comparison
Cost remains a real factor in the Eliquis vs Xarelto decision. For years both were brand-name-only medications with high list prices, and paying out of pocket without insurance could run to several hundred dollars for a monthly supply. The picture has been changing: generic versions of apixaban and rivaroxaban have been entering the U.S. market, which over time tends to lower prices, though availability and pricing can vary by pharmacy and by your insurance. Prices change frequently, so verify the current cost with your own pharmacy rather than relying on any published figure.
Both manufacturers have historically offered copay assistance programs for eligible, commercially insured patients, and pharmacy discount programs may help others. For Medicare patients, coverage falls under Part D, and out-of-pocket costs depend on your specific plan. If cost is a barrier, talk to your prescriber and pharmacist about assistance programs, generic availability, mail-order pricing, and whether your plan prefers one DOAC over the other on its formulary. Do not skip or ration doses to save money without first asking your care team for help finding an affordable option.
Which One Is Right for You?
The choice between Eliquis vs Xarelto depends on your specific medical situation, and it is a decision for you and your prescriber, not something to settle from an article. Many cardiologists and hematologists have shifted toward Eliquis as a frequent default, citing the ARISTOTLE results and real-world bleeding data. Even so, Xarelto remains an excellent option, particularly for patients who value once-daily dosing or whose insurance makes it more affordable.
Eliquis may be considered when bleeding risk is higher, such as in older adults or those with a history of GI bleeding. Xarelto’s once-daily schedule may suit patients for whom a twice-daily regimen is hard to maintain. Patients with kidney disease need careful evaluation regardless of which DOAC is considered, because both drugs are partly cleared by the kidneys and may require dose adjustment or an alternative. The National Kidney Foundation emphasizes monitoring kidney function in patients on DOACs. Your prescriber weighs all of these factors together.
Drug Interactions to Know About
Both Eliquis and Xarelto interact with certain other medications. Strong inhibitors of the CYP3A4 and P-glycoprotein pathways, such as some antifungals (for example ketoconazole and itraconazole), certain HIV medications, and some antibiotics, can raise blood levels of either drug and increase bleeding risk. Conversely, strong inducers such as rifampin and certain antiseizure medications (for example phenytoin and carbamazepine) can lower drug levels and reduce the anticoagulant effect, raising clot risk.
Combining either DOAC with other blood thinners, antiplatelet drugs such as aspirin or clopidogrel, or NSAIDs such as ibuprofen or naproxen can significantly increase bleeding risk. Many clinicians suggest acetaminophen as a preferred pain reliever for patients on anticoagulants, but confirm with your own doctor. Always tell every healthcare provider, including dentists, surgeons, and pharmacists, that you take a blood thinner, and check before starting any new prescription, over-the-counter product, or supplement.
Frequently Asked Questions
Is Eliquis safer than Xarelto?
Clinical and real-world data suggest Eliquis may carry a lower risk of major bleeding, particularly gastrointestinal bleeding, compared with Xarelto. The ARISTOTLE trial showed favorable safety outcomes for Eliquis versus warfarin, while Xarelto showed bleeding rates broadly similar to warfarin. Both are considered safe and effective when prescribed and monitored appropriately for the right patient.
Can you switch from Xarelto to Eliquis?
Switching between DOACs is done under medical supervision and should never be attempted on your own. Your prescriber will tell you exactly when to take the last dose of one drug and the first dose of the other so you are neither over- nor under-anticoagulated during the transition.
Do Eliquis and Xarelto require blood monitoring?
Neither drug requires the regular INR testing that warfarin demands, which is a major advantage of DOACs. However, your doctor will still order periodic blood work to check kidney function, liver function, and blood counts, and to guide ongoing dosing.
What should I do if I miss a dose?
Follow the specific instructions your prescriber or pharmacist gave you, and never double up to make up for a missed dose without professional guidance. Because missing doses of any anticoagulant can temporarily raise clot risk, consistency matters; ask your care team to help you build a reliable routine.
Are there foods to avoid with Eliquis or Xarelto?
Unlike warfarin, neither Eliquis nor Xarelto requires strict vitamin-K dietary limits. However, alcohol and grapefruit may affect bleeding risk or drug levels for some people. Read our detailed guides on foods to avoid with Eliquis and foods to avoid with Xarelto for more, and check with your prescriber.
The Bottom Line: Eliquis (apixaban) and Xarelto (rivaroxaban) are both Factor Xa inhibitor DOACs used for stroke prevention in atrial fibrillation and for treating and preventing clots. The most practical difference is that Eliquis is generally taken twice daily and Xarelto once daily, with larger Xarelto doses taken with food; your prescriber sets your exact dose. Both carry boxed warnings: do not stop abruptly, because that raises stroke and clot risk, and there is a risk of spinal blood clots with spinal anesthesia or spinal taps. The main danger of both is bleeding, so learn the warning signs and seek care right away, calling 911 for severe bleeding. Never start, stop, switch, or adjust these medicines on your own. This article is for general education and is not medical advice; work with your cardiologist or prescriber to decide what is right for you. For more, visit our medical conditions guide.
Sources
- U.S. Food and Drug Administration – Eliquis (apixaban) prescribing information, including boxed warnings (accessdata.fda.gov)
- U.S. Food and Drug Administration – Xarelto (rivaroxaban) prescribing information, including boxed warnings (accessdata.fda.gov)
- DailyMed, National Library of Medicine – Apixaban and rivaroxaban label information (dailymed.nlm.nih.gov)
- MedlinePlus, National Library of Medicine – Apixaban and rivaroxaban patient drug information (medlineplus.gov)
- Mayo Clinic – Anticoagulant (blood thinner) drug information and precautions (mayoclinic.org)
- Cleveland Clinic – DOACs and anticoagulation safety (clevelandclinic.org)
- National Kidney Foundation – Anticoagulation and kidney function (kidney.org)