Study to Gather Information About the Safety of Oral Anticoagulation Drugs and How Well These Drugs Work in Real World for Patients With Non-valvular Atrial Fibrillation (Irregularly Heart Beats Which is Not Caused by a Heart Valve Problem) (REATTAIN)

Real-world Evidence for Non-valvular Atrial Fibrillation Patients Treated With Oral Anticoagulation in the Nordics

Oral anticoagulant (OAC) treatment with either vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulants (NOACs) is essential in patients with atrial fibrillation for the prevention of stroke or systemic embolism (SE) a condition that happens when a blood clot forms elsewhere in the body and travels through the blood stream to plug another vessel. While there are significant number of real-world publications on the use and outcomes of NOACs for stroke prevention, evidence from routine clinical practice on the use and outcomes of reduced doses of NOACs is scarce. By evaluating routine clinical practice data from national registers in Denmark, Finland, Norway and Sweden, researchers want to gather information about the safety and how well reduced doses of NOACs work in patients with irregularly heartbeats which are not caused by a heart valve problem (non-valvular atrial fibrillation, NVAF). As a primary aim of this study, treatment with low doses of NOACs (Xarelto [generic name rivaroxaban], Eliquis [generic name apixaban] or Pradaxa [generic name dabigatran]) will be compared with VKAs (warfarin) in Nordic patients with NVAF to assess the occurrence of stroke and systemic embolism [effectiveness]) and intracranial hemorrhage a type of bleeding that occurs inside the skull [safety]).

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: Rivaroxaban (Xarelto); Drug: Apixaban; Drug: Dabigatran; Drug: Warfarin

• Study Type: Observational
• Enrollment (Actual): 134897

Contacts and Locations

Study Locations

• Sweden
  • Multiple Locations, Sweden
    • Many Locations

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with NVAF who initiate treatment with oral anticoagulants (OACs, either VKAs or NOACs)

Description

Inclusion Criteria:

• Patients with a qualifying oral OAC dispensed during the study period
• A primary diagnosis indicative of atrial fibrillation during the baseline period

Exclusion Criteria:

• Age < 18 years at index date
• Died on index date
• A diagnosis of valvular disease, pregnancy, transient cause of atrial fibrillation or venous thromboembolism in the baseline period or on the index date
• Hip or knee replacement surgery in the 60 days prior to or on the index date
• A dispensed prescription of heparin or fondaparinux in the 60 days prior to or on the index date
• A diagnosis of end-stage kidney disease or renal replacement therapy in the baseline period or on the index date
• More than one dispensed OAC (any dose of rivaroxaban, apixaban, dabigatran, edoxaban, or warfarin) on the index date
• A dispensed prescription of an OAC (any dose of rivaroxaban, apixaban, dabigatran, edoxaban, or warfarin) during the baseline period

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
Reduced dose NOAC; Participants with NVAF initiating treatment with reduced doses of individual non-vitamin K antagonist oral anticoagulants (NOACs)	Drug: Rivaroxaban (Xarelto); NOAC, reduced dose; Drug: Apixaban; NOAC, reduced dose; Drug: Dabigatran; NOAC, reduced dose
Vitamin K antagonists (VKA); Participants with NVAF initiating treatment with vitamin K antagonists (VKA)	Drug: Warfarin; VKA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with ischemic stroke (IS) or systemic embolism (SE)	Evaluation will be done in participants treated with reduced doses of individual NOACs and with VKA	Retrospective analysis from 2010 - 2018
Number of participants with intracranial haemorrhage (ICH)	Evaluation will be done in participants treated with reduced doses of individual NOACs and with VKA	Retrospective analysis from 2010 - 2018

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with severe IS	Evaluation will be done in participants treated with reduced doses of individual NOACs	Retrospective analysis from 2010 - 2018
Number of participants with fatal bleeding	Evaluation will be done in participants treated with reduced doses of individual NOACs	Retrospective analysis from 2010 - 2018
Number of participants with acute kidney injury (AKI) / kidney failure	Evaluation will be done in participants treated with reduced doses of individual NOACs and with VKA	Retrospective analysis from 2010 - 2018
Time from initiation of treatment to discontinuation or switching of treatment	Evaluation will be done in participants treated with reduced doses of individual NOACs and with VKA	Retrospective analysis from 2010 - 2018

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Johnson & Johnson

Publications and helpful links

Helpful Links

• Click here for access to information about Bayer's transparency standards and Bayer studies

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2020
• Primary Completion (Actual): September 30, 2023
• Study Completion (Actual): September 30, 2023

Study Registration Dates

• First Submitted: January 17, 2020
• First Submitted That Met QC Criteria: January 29, 2020
• First Posted (Actual): January 31, 2020

Study Record Updates

• Last Update Posted (Actual): August 1, 2024
• Last Update Submitted That Met QC Criteria: July 30, 2024
• Last Verified: July 1, 2024

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; Dabigatran; Apixaban; Warfarin
• Other Study ID Numbers: 20030

Plan for Individual participant data (IPD)

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

IPD Plan Description

Availability of this study's data will later 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.vivli.org 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 member 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