Use of Direct Oral Anticoagulants in UK

Pattern of Use of Direct Oral Anticoagulants in Non-valvular Atrial Fibrillation Patients in UK General Practices

Many people who suffer from irregular heartbeats (atrial fibrillation) which might cause stroke, need to take blood thinners to prevent it. It is important to prescribe the correct dose of blood thinners to the right patients to ensure the treatment works however avoiding complications. In the recent years, new blood thinners have been available; they require less laboratory tests and fewer visits to a doctor compared to older therapies. This study will look at how the general practitioners in the UK prescribe blood thinners according to the instructions given by the product manufacturer. We will use primary care data that is routinely collected by the general practitioners about their patients but without any possibility to identify individual patients. The results will help us to understand the magnitude of deviation from instructions in order to ensure that the patients benefit from the treatment.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Drug: Rivaroxaban (Xarelto, BAY59-7939); Drug: Dabigatran; Drug: Apixaban

• Study Type: Observational
• Enrollment (Actual): 31336

Contacts and Locations

Study Locations

• United Kingdom
  • Multiple Locations, United Kingdom
    • Many Locations

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

Population based on primary care databases representative of the UK population.

Description

Inclusion Criteria:

• All patients aged >= 18 years with at least one year of enrollment with the primary care practice and one year since first health contact recorded in the database THIN(The Health Improvement Network) or CPRD(Clinical Practice Research Datalink) prior to index prescription date will be included.
• Patients with first prescription of DOACs (rivaroxaban, dabigatran, apixaban) during the study period.
• Diagnosis NVAF (any time prior index date or within the 2 weeks after the index date)

Exclusion Criteria:

• Patients having the history of valvular replacement or mitral stenosis (prior to index date or 2 weeks after index-date)
• Patients who have any record of being prescribed their index drug prior to the enrolment period or who qualify as members of more than one cohort on the same day.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Stroke Prevention with Rivaroxaban in NVAF Patients; All NVAF patients above 18 years for age prescribed with Rivaroxaban during the study period	Drug: Rivaroxaban (Xarelto, BAY59-7939); Oral direct factor Xa inhibitors, 15mg and 20mg tablets QD
Stroke Prevention with Dabigatran in NVAF Patients; All NVAF patients above 18 years for age prescribed with Dabigatran during the study period	Drug: Dabigatran; Oral direct thrombin inhibitors, 75mg and 150mg capsules BID
Stroke Prevention with Apixaban in NVAF Patients; All NVAF patients above 18 years for age prescribed with Apixaban during the study period	Drug: Apixaban; Oral direct factor Xa inhibitors, 2.5mg and 5 mg tablets BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Demographic Characteristics	Age; Sex; Smoking status (previous 6 months); Body mass index (previous 6 months); Blood pressure history (previous 12 months); Number of patients that are naïve vs non-naïve For non-naïve: type and duration of anticoagulant used before index date	6 years
Risk factor categories	C(Congestive heart failure) H(Hypertension)A(Age)D(Diabetes Mellitus)S2(Prior Stroke or TIA) score; C(Congestive heart failure) H(Hypertension)A2(Age ≥75 years)D(Diabetes Mellitus)S2 V(Vascular disease)A(Age 65-74 years)SC(Sex category); H(Hypertension)A(Abnormal renal and liver function)S(Stroke)B(Bleeding)L(Labile INRs)E(Elderly)D(Drugs or alcohol) score; INR(International Normalized Ratio) measurement	6 years
Previous medical history	Acute MI(Myocardial Infarction); Stroke or TIA(Transient Ischemic Attack); Systemic peripheral arterial embolism; Coronary artery disease; Congestive heart disease; Hypertension; Diabetes Renal disease (eGFR) or ACR (Albumin/Creatinine Ratio)	12 months prior to index date
Previous medication history	Anti-arrhythmics; Statins; Anti-platelets; Beta-blockers; ACE(Angiotensin-Converting-Enzyme) inhibitors; Anti-diabetic agents; Non-steroidal anti-inflammatory drugs (NSAIDs); Antacids; Histamine receptor antagonists; Proton pump inhibitors (PPIs); Disease-modifying anti-rheumatic drugs (DMARDs); Antidepressants; Antipsychotic agents; Oral contraceptives; Hormone replacement therapy (HRT); Strong inhibitors of Cytochrome P450 or P-GP; Strong inducers of CYP3A4	12 months prior to index date
Previous use of VKA	Warfarin; Other Vitamin K antagonist(s)	Ever prior to index date
Concurrent co-medication	Anti-coagulants; Aspirin; Clopidogrel; Other	6 years
Daily dose	DOACs(new oral anticoagulants ) for stroke prevention in NVAF(Non valvular Atrial Fibrillation) patients including those with renal impairment	6 years
Dose posology	DOACs for stroke prevention in NVAF patients including those with renal impairment	6 years
Naive status and Non-naive status	DOACs for stroke prevention in NVAF patients including those with renal impairment	6 years
Treatment Duration	DOACs for stroke prevention in NVAF patients including those with renal impairment	6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-trends	Characteristics of first-time use of DOACs in NVAF patients	6 years

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Janssen Scientific Affairs, LLC

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2017
• Primary Completion (Actual): October 16, 2017
• Study Completion (Actual): April 16, 2019

Study Registration Dates

• First Submitted: April 13, 2017
• First Submitted That Met QC Criteria: April 13, 2017
• First Posted (Actual): April 18, 2017

Study Record Updates

• Last Update Posted (Actual): April 17, 2020
• Last Update Submitted That Met QC Criteria: April 16, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Stroke Prevention in NVAF patients
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban; Dabigatran; Apixaban
• Other Study ID Numbers: 19330

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• 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