Rivaroxaban vs Warfarin in Patients With Mechanical Heart Valves

Rivaroxaban vs. Warfarin in Patients With Mechanical Heart Valves

Warfarin is the standard anticoagulant used for patients with mechanical heart valves; however, its use is complicated by a narrow therapeutic window, frequent drug and dietary interactions, and the need for regular international normalized ratio (INR) monitoring. In resource-limited settings such as Pakistan, many patients have difficulty accessing reliable INR testing, which can result in suboptimal anticoagulation and increased risks of thromboembolic or bleeding complications.

Rivaroxaban, a direct oral factor Xa inhibitor, offers predictable pharmacokinetics and does not require routine laboratory monitoring, making it a potentially more convenient option for patients with limited access to INR testing.

This prospective comparative study aims to evaluate rivaroxaban as an alternative to warfarin in patients with mechanical heart valves. Sixty adult patients will be enrolled and followed for one year, comparing the incidence of thromboembolic and bleeding events between patients treated with rivaroxaban and those maintained on dose-adjusted warfarin.

Study Overview

• Status: Enrolling by invitation
• Conditions: Valvular Heart Disease Patients
• Intervention / Treatment: Drug: Rivoroxaban; Drug: Warfarin

Detailed Description

Patients with mechanical heart valves require lifelong anticoagulation to prevent thromboembolic complications such as prosthetic valve thrombosis and systemic embolism. For decades, vitamin K antagonists, particularly warfarin, have been the standard therapy for this population. Warfarin remains the standard anticoagulant therapy for patients with mechanical heart valve replacements, while the use of rivaroxaban in this population is still under investigation.While effective, warfarin therapy presents several challenges, including a narrow therapeutic window, variable dose response, numerous drug-drug and drug-food interactions, and the requirement for regular monitoring of the international normalized ratio (INR). Maintaining therapeutic anticoagulation can therefore be difficult, and both under- and over-anticoagulation may lead to serious complications such as thromboembolism or major bleeding.

These challenges are particularly pronounced in low- and middle-income countries, including Pakistan, where access to reliable and frequent INR testing may be limited. Many patients receiving mechanical valve replacements travel long distances to tertiary care centers for follow-up and may rely on local healthcare providers who do not have access to standardized coagulation monitoring facilities. As a result, inadequate INR monitoring can lead to poorly controlled anticoagulation and increased rates of prosthetic valve complications requiring emergency intervention.

Direct oral anticoagulants (DOACs) have emerged as an important alternative to vitamin K antagonists in several thromboembolic conditions. Rivaroxaban, a direct factor Xa inhibitor, has predictable pharmacokinetics, rapid onset of action, and fewer dietary and drug interactions compared with warfarin. Importantly, rivaroxaban does not require routine laboratory monitoring, which may make it particularly advantageous in settings where access to INR testing is limited. Rivaroxaban has demonstrated efficacy and safety in large clinical trials for the treatment and prevention of venous thromboembolism and for stroke prevention in non-valvular atrial fibrillation.

However, the use of DOACs in patients with mechanical heart valves remains an area of ongoing investigation. Limited early clinical studies and experimental models have suggested that factor Xa inhibition may provide effective anticoagulation in the thrombogenic environment associated with mechanical prosthetic valves. Preclinical studies using animal models have demonstrated reduced thrombus formation and platelet deposition with rivaroxaban, supporting the biological plausibility of this approach. Small pilot clinical investigations have also explored the feasibility of rivaroxaban in selected patients with mechanical valves, although evidence remains limited and further clinical evaluation is required.

Rawalpindi Institute of Cardiology is a tertiary cardiac center where a large number of patients undergo mechanical valve replacement each year. Many of these patients experience difficulty maintaining stable anticoagulation with warfarin because of limited access to INR monitoring, socioeconomic constraints, or complications related to warfarin therapy. These challenges provide a strong clinical rationale for exploring alternative anticoagulation strategies that may be more practical for patients in resource-limited settings.

This prospective comparative study is designed to evaluate rivaroxaban as a potential alternative anticoagulant in patients with mechanical heart valves who experience difficulty with conventional warfarin therapy. Patients receiving rivaroxaban will be followed and compared with a control group of patients continuing standard dose-adjusted warfarin therapy. Participants will be monitored over a one-year follow-up period to evaluate the incidence of thromboembolic and bleeding events, as well as overall treatment safety.

Clinical follow-up will include regular patient assessments and echocardiographic evaluation to monitor prosthetic valve function and detect potential thrombotic complications. Safety monitoring will include evaluation for bleeding events, thromboembolic complications, and other adverse outcomes during the follow-up period.

By comparing clinical outcomes between rivaroxaban and warfarin therapy in patients with mechanical heart valves, this study aims to generate preliminary evidence regarding the feasibility and safety of factor Xa inhibition in this high-risk population. If rivaroxaban demonstrates comparable clinical outcomes, it may represent a more convenient and accessible anticoagulation strategy for patients who face significant barriers to regular INR monitoring in resource-limited healthcare environments.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• Pakistan
  • Punjab Province
    • Rawalpindi, Punjab Province, Pakistan, 46000
      • Rawalpindi Institute of Cardiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients (≥18 years) with mechanical heart valves
• History of thromboembolic or bleeding complications while on warfarin or limited access to INR testing
• Ability and willingness to provide informed consent

Exclusion Criteria:

• Contraindication to rivaroxaban
• Hemorrhagic stroke or ischemic stroke within the past 3 months
• Severe renal impairment (creatinine clearance <30 mL/min)
• Increased risk of bleeding due to congenital or acquired disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rivaroxaban; Rivaroxaban Group: Patients will be started on Rivaroxaban 20 mg once daily, as per the standard dose for mechanical heart valves along with Aspirin 75mg once daily Doze will be titrated according to weight.those with weight greater than 80 kg will be given tab rivoroxaban 15 mg BD alongwith asprin 75 mg OD .	Drug: Rivoroxaban; Intervention Arm: Rivaroxaban Participants will receive rivaroxaban as an alternative anticoagulant to warfarin for mechanical heart valves. Rivaroxaban will be administered at 20 mg once daily (or 15 mg twice daily for patients >80 kg), along with aspirin 75 mg once daily unless contraindicated. Initial factor Xa levels will be used to guide dose adjustment, followed by routine clinical evaluation and echocardiographic monitoring. This intervention aims to assess whether rivaroxaban can safely and effectively provide therapeutic anticoagulation in patients who have warfarin-related complications or poor access to INR monitoring.
Active Comparator: warfarin; second arm will be given conventional warfarin conventional	Drug: Warfarin; Patients will be treated with conventional tablet warfarin as per standard protocol and will maintain INR as per AHA guidelines

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Thromboembolic Events	Description: Incidence of participants experiencing at least one thromboembolic event (stroke, TIA, prosthetic valve thrombosis, DVT, or PE) during follow-up. Unit of Measure: Number of participants with ≥1 event; proportion (%)	12 months from treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Major Bleeding	Description: Number of participants experiencing at least one major bleeding event (defined according to ISTH criteria). Unit of Measure: Number of participants; proportion (%)	12 months
Incidence of Clinically Relevant Non-Major Bleeding (if applicable)	Description: Number of participants experiencing at least one clinically relevant non-major bleeding event. Unit of Measure: Number of participants; proportion (%)	12 months
All-Cause Mortality	Description: Number of participants who die from any cause during follow-up. Unit of Measure: Number of deaths; proportion (%)	12 months
Anticoagulation-Related Hospital Visits	Description: Number of hospital or clinic visits related to anticoagulation management during follow-up. Unit of Measure: Number of visits (count)	12 months

Collaborators and Investigators

• Sponsor: Rawalpindi Institute of Cardiology
• Collaborators: Armed Forces Institute of Pathology

Publications and helpful links

General Publications

• Prins MH, Lensing AW, Brighton TA, Lyons RM, Rehm J, Trajanovic M, Davidson BL, Beyer-Westendorf J, Pap ÁF, Berkowitz SD, Cohen AT, Kovacs MJ, Wells PS, Prandoni P. Oral rivaroxaban versus enoxaparin with vitamin K antagonist for the treatment of symptomatic venous thromboembolism in patients with cancer (EINSTEIN-DVT and EINSTEIN-PE): a pooled subgroup analysis of two randomised controlled trials. Lancet Haematol. 2014 Oct;1(1):e37-46. doi: 10.1016/S2352-3026(14)70018-3. Epub 2014 Sep 28. PMID: 27030066.
• Duraes AR, de Souza Lima Bitar Y, Schonhofen IS, Travassos KSO, Pereira LV, Filho JAL, Neto MG, Junior RA, Roever L. Rivaroxaban Versus Warfarin in Patients with Mechanical Heart Valves: Open-Label, Proof-of-Concept trial-The RIWA study. Am J Cardiovasc Drugs. 2021 May;21(3):363-371. doi: 10.1007/s40256-020-00449-3. Epub 2020 Nov 5. PMID: 33150497.
• Roost E, Weber A, Alberio L, Englberger L, Reineke D, Keller D, Nagler M, Carrel T. Rivaroxaban in patients with mechanical heart valves: A pilot study. Thromb Res. 2020 Feb;186:1-6. doi: 10.1016/j.thromres.2019.12.005. Epub 2019 Dec 7. PMID: 31837559.

Helpful Links

• Rivaroxaban versus Warfarin in Patients with Mechanical Heart Valves: Rationale and Design of the RIWA Study - original study-protocol paper describing the design, inclusion/exclusion criteria, endpoints, and methods.
• Effectiveness of rivaroxaban for thromboprophylaxis of prosthetic heart valves in a porcine heterotopic valve model - preclinical animal-model study evaluating rivaroxaban's thromboprophylactic effect on mechanical valves.

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2025
• Primary Completion (Estimated): April 12, 2027
• Study Completion (Estimated): April 12, 2027

Study Registration Dates

• First Submitted: January 20, 2026
• First Submitted That Met QC Criteria: March 3, 2026
• First Posted (Actual): March 6, 2026

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: cardiac surgery; Bleeding; Thromboembolism; mechanical heart valve; Direct Oral Anticoagulant (DOAC)
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Embolism and Thrombosis; Pathological Conditions, Signs and Symptoms; Thromboembolism; Hemorrhage; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pyrans; Coumarins; Benzopyrans; 4-Hydroxycoumarins; Warfarin
• Other Study ID Numbers: RIC/RERC/24/2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No