A Study Using Electronic Health Information to Learn About Rivaroxaban Compared to Warfarin in Participants With Non-valvular Atrial Fibrillation (NVAF) and Diabetes (RIVA-DM)

RIVA-DM: Effectiveness and Safety of Rivaroxaban vs. Warfarin in Nonvalvular Atrial Fibrillation and Diabetes Mellitus: Analysis of Electronic Health Record Data

In people with type 2 diabetes, the body does not make enough of a hormone called insulin or does not use insulin well. This results in high blood sugar levels.

People with diabetes are more likely to have non-valvular atrial fibrillation (NVAF) compared to people who do not have diabetes. Having both NVAF and diabetes can increase the chances of developing other serious health conditions, like blood clots and strokes.

People with NVAF may receive treatments to help lower the risk of blood clots. This can then help to lower the risk of having a stroke. Two of these treatments are rivaroxaban and warfarin.

In this study, the researchers will look at how well rivaroxaban works and how safe it is compared to warfarin in routine clinical practice. The study will include men and women who are at least age 18 and who have NVAF and type 2 diabetes.

The researchers in this study will use the participants' health information from an electronic database.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: Rivaroxaban (Xarelto, BAY59-7939); Drug: Warfarin

• Study Type: Observational
• Enrollment (Actual): 116049

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Whippany, New Jersey, United States, 07981
      • US Optum De-Identified EHR data

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study is using Optum electronic health record (EHR) database. The study population of interest will be US participants with Non-valvular atrial fibrillation (NVAF) and comorbid type 2 diabetes, oral anticoagulation (OAC)-naïve and newly-initiated on rivaroxaban or warfarin, be active in the data set and have received care.

Description

Inclusion Criteria:

• Be ≥18 years of age at the time of anticoagulation initiation
• Have diagnoses of type 2 diabetes and Non-valvular atrial fibrillation (NVAF)
• Have no record of prior oral anticoagulant (OAC) use in the prior 12-months
• Newly initiated on Rivaroxaban or Warfarin (index date)
• Have ≥12-months of electronic health record (EHR) activity prior to the index date and received care documented in the EHR database from at least one provider in the 12-months prior

Exclusion Criteria:

• Evidence of valvular heart disease defined as any rheumatic heart disease, mitral stenosis or mitral valve repair/replacement
• Pregnancy
• Use of rivaroxaban doses other than 15 mg once daily or 20 mg once daily or the presence of other indication(s) for OAC use
• Any prior OAC utilization per written prescription or self-report at baseline

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group A; Participants with diagnoses of type 2 diabetes and non-valvular atrial fibrillation (NVAF) newly-initiated on rivaroxaban	Drug: Rivaroxaban (Xarelto, BAY59-7939); Participants receive rivaroxaban (per written prescription, medication administration or self-report of medication use)
Group B; Participants with diagnoses of type 2 diabetes and non-valvular atrial fibrillation (NVAF) newly-initiated on warfarin	Drug: Warfarin; Participants receive warfarin (per written prescription, medication administration or self-report of medication use)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Composite of stroke or systemic embolism	Up to 8 years
Any major or clinically-relevant nonmajor bleed resulting in hospitalization	Up to 8 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ischemic stroke		Up to 8 years
Systemic embolism		Up to 8 years
Need for revascularization or major amputation of the lower limb		Up to 8 years
Intracranial hemorrhage		Up to 8 years
Critical organ bleeding per ISTH categories	The categories for critical organ bleeding as per ISTH definition are: intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome.	Up to 8 years
Any extracranial bleeding		Up to 8 years
Any hospitalization due to intracranial or critical organ bleeding or a bleed in another location associated with either a 2 g/dL drop in hemoglobin or need for transfusion		Up to 8 years
Doubling of the serum creatinine level from baseline		Up to 8 years
Decrease in eGFR>30% or 40%	Glomerular filtration rate (GRF)	Up to 8 years
Development of an eGFR<15 mL/min or initiation of dialysis	Glomerular filtration rate (GRF)	Up to 8 years
Development of end-stage renal disease per billing codes only		Up to 8 years
Development of urine albumin-to-creatinine ratio (UACR) of 30-300 or >300		Up to 8 years
Development of serum potassium > 5.6 or >6 mg/dL		Up to 8 years
Development of diabetic retinopathy		Up to 8 years
Myocardial infarction		Up to 8 years
All-cause mortality		Up to 8 years
Vascular mortality		Up to 8 years
Major adverse cardiovascular event		Up to 8 years
Composite of stroke, systemic embolism, vascular death		Up to 8 years
Composite of stroke, systemic embolism, myocardial infarction, vascular death		Up to 8 years
Composite stroke, systemic embolism, need for lower limb revascularization or major amputation		Up to 8 years
Composite of >40% decrease in eGFR from baseline, eGFR<15 mL/minute, need for dialysis, renal transplant, major adverse limb event, retinopathy or all-cause death	Glomerular filtration rate (GRF)	Up to 8 years
New-onset vascular dementia		Up to 8 years

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Janssen Research & Development, LLC

Publications and helpful links

General Publications

• Costa OS, O'Donnell B, Vardar B, Abdelgawwad K, Brescia CW, Sood N, Coleman CI. Kidney, limb and ophthalmic complications, and death in patients with nonvalvular atrial fibrillation and type 2 diabetes prescribed rivaroxaban or warfarin: an electronic health record analysis. Curr Med Res Opin. 2021 Sep;37(9):1493-1500. doi: 10.1080/03007995.2021.1947217. Epub 2021 Jul 8.

Helpful Links

• Click here to find results for studies related to Bayer products

Study record dates

Study Major Dates

• Study Start (Actual): August 21, 2020
• Primary Completion (Actual): July 31, 2021
• Study Completion (Actual): July 31, 2021

Study Registration Dates

• First Submitted: August 10, 2020
• First Submitted That Met QC Criteria: August 10, 2020
• First Posted (Actual): August 11, 2020

Study Record Updates

• Last Update Posted (Actual): June 15, 2022
• Last Update Submitted That Met QC Criteria: June 13, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban; Warfarin
• Other Study ID Numbers: 21449; EUPAS36634 (Other Identifier: ENCePP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No