What is the incidence of hematuria in patients taking Eliquis (apixaban)?

Incidence of Hematuria in Patients Taking Eliquis (Apixaban)

Hematuria occurs in 1.7% of patients treated with apixaban for DVT/PE, and in 1.4% of patients undergoing hip or knee replacement surgery, based on FDA-approved prescribing information. 1

Documented Incidence Rates by Clinical Indication

Treatment of DVT and PE (AMPLIFY Study)

• Hematuria occurred in 1.7% of apixaban-treated patients (46 out of 2,676 patients) compared to 3.8% in the enoxaparin/warfarin group 1
• This represents a lower rate than traditional anticoagulation with warfarin 1

Extended Treatment of DVT and PE (AMPLIFY-EXT Study)

• Hematuria occurred in 1.4% of patients on apixaban 2.5 mg twice daily (12 out of 840 patients) 1
• Hematuria occurred in 2.1% of patients on apixaban 5 mg twice daily (17 out of 811 patients) 1
• Placebo group had 1.1% incidence, demonstrating dose-dependent relationship 1

Hip or Knee Replacement Surgery

• Hematuria (including respective laboratory parameters) occurred in approximately 1% of patients receiving apixaban 2.5 mg twice daily for thromboprophylaxis 1
• This was comparable to enoxaparin-treated patients 1

Real-World Population Data

Overall Hematuria-Related Complications

• Patients on antithrombotic agents experience 123.95 hematuria-related events per 1,000 person-years compared to 80.17 events per 1,000 person-years in unexposed patients (incidence rate ratio 1.44) 2
• This translates to an additional 43.8 events per 1,000 person-years attributable to anticoagulation 2

Breakdown by Healthcare Utilization

• Urologic procedures for hematuria: 105.78 events per 1,000 person-years (IRR 1.37) 2
• Hospitalizations for hematuria: 11.12 events per 1,000 person-years (IRR 2.03) 2
• Emergency department visits for hematuria: 7.05 events per 1,000 person-years (IRR 2.80) 2

Risk Factors That Increase Hematuria Incidence

Dose-Related Factors

• Higher apixaban doses (5 mg vs 2.5 mg) increase bleeding risk by 63% in patients with severe chronic kidney disease (subdistribution hazard ratio 1.63), including hematuria 3
• The 5 mg dose was associated with 4.9 bleeding events per 100 person-years versus 2.9 events with 2.5 mg 3

Renal Impairment

• Patients with severe chronic kidney disease (stage 4/5) have prolonged apixaban half-life (17 hours versus 12 hours in normal renal function), increasing bleeding risk including hematuria 4
• Apixaban is 27% renally cleared, the lowest among direct oral anticoagulants 4

Combination Therapy

• Patients on both anticoagulants and antiplatelet agents experience 191.61 hematuria-related events per 1,000 person-years (IRR 10.48 compared to unexposed patients) 2
• This represents a 10-fold increase in hematuria complications with dual therapy 2

Clinical Significance of Hematuria on Apixaban

Diagnostic Workup Necessity

• Patients on anticoagulants who develop hematuria have significant pathological findings in 59% of cases (17 of 29 patients), including carcinoma, calculi, renal infarction, and infection 5
• Bladder cancer diagnosis within 6 months is more common in anticoagulated patients with hematuria (0.70% vs 0.38%; odds ratio 1.85) 2
• A thorough urologic evaluation should be conducted despite anticoagulation status, as pathological lesions are frequently discovered 5

Rare but Serious Complication

• Anticoagulant-related nephropathy (ARN) with apixaban has been reported, manifesting as acute kidney injury with severe acute tubular necrosis and occlusive red blood cell casts 6
• This represents major discrepancy between degree of glomerular injury and glomerular hematuria 6
• Monitoring kidney function is recommended after initiation of apixaban therapy 6

Important Caveats

The incidence of hematuria varies significantly based on clinical context, dose, renal function, and concomitant medications. 1, 2, 3 The FDA-reported rates from clinical trials (1.4-2.1%) likely underestimate real-world incidence, as population-based studies show substantially higher rates of hematuria-related complications requiring medical intervention. 2 Clinicians should not dismiss hematuria in anticoagulated patients as merely a medication side effect, as underlying urologic pathology is present in the majority of cases. 5