Low-dose Versus Standard-dose Rivaroxaban in Elderly Patients With Atrial Fibrillation

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of low-dose versus standard-dose rivaroxaban anticoagulation therapy in elderly patients with atrial fibrillation.

Official Title
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The Efficacy and Safety of Low-dose Versus Standard-dose Rivaroxaban in Elderly Patients With Atrial Fibrillation

Conditions
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Atrial Fibrillation, Anticoagulant Adverse Reaction, Stroke, Major Adverse Cardiac Events

Intervention / Treatment
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* Drug: low-dose rivaroxaban
* Drug: Standard-dose rivaroxaban


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Age ≥70 years Patients with atrial fibrillation (atrial fibrillation rhythm of at least 30 seconds duration recorded by ECG or Holter within 6 months) CHA2DS2-VASc score ≥2 in men and ≥3 in women Exclusion criteria： Moderate-to-severe mitral stenosis or prior valve replacement surgery Severe stroke event within 6 months or any stroke within 14 days Major stroke events were defined as those with a Modified Rankin Scale score of 3-5. Score 3: moderately disabled, requiring some assistance but walking without assistance; Score 4: severe disability, unable to walk independently, unable to meet their own needs without the help of others; Score 5: severe disability, bedridden, incontinent, requiring ongoing care and attention High or increasing risk for bleeding i. Traumatic surgery that has been completed within the last 3 months or is planned within the next 3 months ii. Previous severe intracranial, intraocular, spinal cord, retroperitoneal, or nontraumatic intra-articular hemorrhage. iii. Gastrointestinal bleeding within the past year iv. Symptomatic or gastroscopic peptic ulcer within the last month v. Hemorrhagic constitution or coagulopathy vi. Use of fibrinolytic agents within 48 hours of enrollment vii. Difficult-controlled hypertension (180mm Hg systolic and/or 100 mm Hg diastolic) viii. Diagnosis of malignancy within 6 months or radiotherapy Transient atrial fibrillation due to reversible triggers (e.g., after cardiac surgery, pulmonary embolism, untreated hyperthyroidism) Catheter ablation or surgery for AF is planned Severe renal impairment (estimated creatinine clearance ≤ 30 mL/min) Active infective endocarditis Active liver disease Including but not limited to: i. Persistent ALT, AST, Alk Phos > 2×U; ii. Known active hepatitis C (HCV RNA positive); iii. Active hepatitis B (HBs antigen +, anti-HBc IgM+); iv. Active hepatitis A anemia (hemoglobin level <100g/L) or thrombocytopenia (thrombocytopenia count <100 × 10^9/L) patients enrolled in another study drug trial within the past 30 days or at the same time Patients whose condition warrants standard-dose anticoagulation Other conditions deemed by the investigator to be inappropriate for enrollment

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-dose rivaroxaban<br>15mg q.d. rivaroxaban for 2 years after randomization. The dose should be reduced in the following special conditions: 1. Creatinine clearance <50 mL/min; 2. Body weight ≤60kg; 3. Age ≥80 years old. In the low-dose group, the dose was reduced from the usual 15mg q.d. to 10mg q.d. . | Drug: low-dose rivaroxaban<br>* Rivaroxaban 15mg q.d. (The dose should be reduced to 10mg q.d. in the following special populations: 1. Creatinine clearance <50 mL/min; 2. Body weight ≤60kg; 3. Age ≥80 years old)<br>|
| Active Comparator: Standard-dose rivaroxaban<br>20mg q.d. rivaroxaban for 2 years after randomization. The dose should be reduced in the following special conditions: 1. Creatinine clearance <50 mL/min; 2. Body weight ≤60kg; 3. Age ≥80 years old. In the standard-dose group, the dose was reduced from the 20mg q.d. to 15mg q.d. . | Drug: Standard-dose rivaroxaban<br>* Rivaroxaban 20mg q.d. (The dose should be reduced to 15mg q.d. in the following special populations: 1. Creatinine clearance <50 mL/min; 2. Body weight ≤60kg; 3. Age ≥80 years old)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major adverse cardiovascular and cerebrovascular events(MACCE) | A composite endpoint of clinical events including cardiovascular death, myocardial infarction, stroke, and systemic embolism was recorded within 2 years after randomization | At 24-month after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Net clinical benefit | All-cause death, myocardial infarction, stroke, transient ischemic attack, systemic embolism, and major bleeding events within 2 years after randomization | At 24-month after randomization |