Apixaban Drug Utilization Study In Stroke Prevention In Atrial Fibrillation (Spaf) (SPAF)

APIXABAN DRUG UTILIZATION STUDY IN STROKE PREVENTION IN ATRIAL FIBRILLATION (SPAF)

Apixaban is a direct anticoagulant, which inhibits the factor Xa. Its clinical efficiency in prevention of stroke and systemic embolism in adult patients with NVAF (non/valvular atrial fibrillation) was demonstrated as well as has shown better safety profile compared with warfarin. A Drug Utilization study will evaluate whether this drug has been used in accordance with the approved indication and recommendations described in the summary of product characteristics (SmPC) and estimate possible misuse or overuse apixaban.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: apixaban; Drug: VKA; Drug: dabigatran; Drug: rivaroxaban

Detailed Description

The primary research question is to evaluate the apixaban utilization according to the approved SPAF indication and recommendations by EMA.

In addition a comparison with a cohort of NVAF patients treated with VKA, dabigatran and rivaroxaban for the SPAF indication will also be performed.

Objective 1: To characterize patients using apixaban according to demographics, comorbidity, risk of thromboembolic events (CHADS2 and CHA2DS2-Vasc scores), risk of bleeding events (HAS-BLED score), comedications and compare it with the profile of patients treated with VKA, dabigatran and rivaroxaban.

Objective 2: Describe the level of appropriate usage according to the posology recommended in the apixaban SmPC.

Objective 3: Describe the potential interactions with other drugs prescribed concomintatly according with the SmPC recommendations.

Objective 4: Estimate the level of apixaban adherence by the medication possession ratio (MPR) and discontinuation rates and compare it with VKA, dabigatran and rivaroxaban cohort.

Objective 5: To analyze INR (International Normalized Ratio) values during the last 12 months and to obtain TTR (Time in Therapeutic Range) values in patients previously treated with VKA, and during the whole study period for those in the cohort treated with VKA.

• Study Type: Observational
• Enrollment (Actual): 51690

Contacts and Locations

Study Locations

• Spain
  • Cataluña
    • Barcelona, Cataluña, Spain, 8007
      • IDIAP Jordi Gol

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

SIDIAP currently collects information from 274 primary health care centers, including more than 5.8 million patients, about 80 % of the Catalonia population, or more than 10 % of the Spanish population covered by the Catalan Institute of Health.

The study population for these cohorts includes all eligible subjects from the source population with a first -recorded prescription of apixaban VKA, dabigatran or rivaroxaban for the SPAF indication, registered in SIDIAP database and diagnosis of NVAF for study period.

Description

Inclusion Criteria:

1. Patients more than 18 years-old.
2. Patients diagnosed with NVAF registered in primary care according to ICD-10.
3. Patients initiating apixaban (naïve or VKA experienced), VKA (naïve or VKA experienced), dabigatran or rivaroxaban for the SPAF indication.
4. Continuous enrolment in the 12 months pre-index.

Exclusion Criteria:

1. Patients with valvular heart disease (ICD 10: I05.0-I05.09, I08.0-I08.9) including patients with mitral prosthetic valves.
2. Lost to follow-up (e.g. transfer to primary care center non-ICS).

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1. Apixaban; Patients who are on treatment with apixaban. 1a. patients who have initiated with apixaban as treatment naïve (no prior prescription of VKA previous to the 12 months before index date). 1b. patients who previously have been treated with VKA in the 12 months before index date.	Drug: apixaban; current or new medication
Group 2. VKA; Patients who are on treatment with VKA. 2a. patients who have initiated with VKA as treatment naïve (no prior prescription of VKA previous to the 12 months before index date). 2b. patients who previously have been treated with VKA in the 12 months before index date.	Drug: VKA; current or new medication
Group 3. Dabigatran; Patients who are on treatment with dabigatran. 3a. patients who have initiated with dabigatran as treatment naïve (no prior prescription of VKA previous to the 12 months before index date). 3b. patients who previously have been treated with VKA in the 12 months before index date.	Drug: dabigatran; current or new medication
Group 4. Rivaroxaban; Patients who are on treatment with rivaroxaban. 4a. patients who have initiated with rivaroxaban as treatment naïve (no prior prescription of VKA previous to the 12 months before index date). 4b. patients who previously have been treated with VKA in the 12 months before index date.	Drug: rivaroxaban; current or new medication

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants by Their Sociodemographic Characteristics: Smoking Habit	Socio-demographics were characteristics of a population. One of the socio-demographics characteristics included smoking habit.	Day 1
Number of Participants by Their Sociodemographic Characteristics: Alcoholic Habit	Socio-demographics were characteristics of a population. One of the socio-demographics characteristics included alcoholic habit.	Day 1
Number of Participants by Their Sociodemographic Characteristics: MEDEA	Socio-demographics were characteristics of a population. One of the socio-demographics characteristics included MEDEA. MEDEA was a deprivation index that was associated with overall mortality in urban areas. It included factors like job, education, housing conditions and single parent homes. The MEDEA index was categorized in quintiles for urban areas, with quintile 1 corresponding to the least deprived population and quintile 5, the most deprived.	Day 1
Number of Participants by Their Sociodemographic Characteristics: Body Mass Index (BMI)	Socio-demographics were characteristics of a population. One of the socio-demographics characteristics included BMI. BMI was defined as an index for assessing overweight and underweight and was obtained by dividing body weight in kilograms (kg) by height in meters squared (m^2).	Day 1
Number of Participants by Comorbidity	Comorbidity was defined as the presence of one or more additional diseases or disorders co-occurring with (that is, concomitant or concurrent with) a primary disease or disorder.	Up to 12 months after date of first prescription
Risk of Bleeding Events: HAS-BLED Score	Risk of bleeding events was assessed by using HAS-BLED score. HAS-BLED was a scoring system that was developed to assess 1 year risk of occurrence of major hemorrhage. HAS-BLED score was assessed by combining score of 9 risk factors: hypertension history, renal disease, liver disease, stroke history, prior major bleeding or predisposition to bleeding, labile international normalized ratio (INR), age >65 years, medication usage predisposing to bleeding and alcohol or drug usage history. The total score ranged from 0 to 9 where 0 = low risk of bleed per 100 participants-year and >3 = high risk of bleed per 100 participants-year.	Up to 12 months prior to enrollment
Risk of Thromboembolic Events: CHADS2 Score	Thromboembolic events were defined as an embolic stroke that occurred when a blood clot that formed elsewhere in the body breaks loose and travels to the brain via bloodstream. Risk of thromboembolic events was calculated using CHADS2 score. CHADS2 score was assessed by combining score of 5 risk factors (congestive heart failure history, hypertension history, age >=75 years, diabetes mellitus history and stroke/transient ischemic attack symptoms previously). Total CHADS2 score ranged from 0-6 where 0 =low risk and 6 =high risk of stroke.	Up to 12 months prior to enrollment
Risk of Thromboembolic Events: CHA2DS2Vasc Score	Thromboembolic events were defined as an embolic stroke that occurred when a blood clot that formed elsewhere in the body breaks loose and travels to the brain via bloodstream. Risk of thromboembolic events was calculated using CHA2DS2Vasc score. CHA2DS2Vasc score was assessed by combining score of 8 risk factors (female, >=65 and <75 years, congestive heart failure history, hypertension history, diabetes mellitus history, vascular disease history, age >=75 years and stroke/TIA symptoms previously). Total CHA2DS2Vasc score ranged from 0-9 where 0=low risk and 9=high risk of stroke.	Up to 12 months prior to enrollment
Number of Participants by Comedications	Comedication was defined as the second or alternative medication used to relieve the side-effects of another medicine.	Up to 30 days after date of first prescription
Number of Participants With Apixaban Adherence With VKA, Dabigatran and Rivaroxaban as Assessed by Medication Possession Ratio (MPR)	MPR was one of the methods of measuring adherence and was defined as the ratio of all days supply to elapsed days, during the 12-month observation period. All days supply defined as sum of number of days supply between the start date and last prescription dispensed. Elapsed days defined as number of days between the start date and the last prescription dispensed. There were three categories of adherence: poor defined as <80% of MPR, good defined as between 80% and 120% of MPR and over adherence defined as >120% of MPR.	Up to 12 months after date of first prescription
Number of Participants With Apixaban Adherence With VKA, Dabigatran and Rivaroxaban as Assessed by Discontinuation Throughout the Year	Discontinuation rate was defined as the lack of subsequent prescription of the index drugs within 2 months after last supply day of the last prescription. It was analyzed by calculating the treatment withdrawal or switch rate.	Up to 12 months after date of first prescription
Apixaban Adherence With VKA, Dabigatran and Rivaroxaban by Number of Defined Daily Dose (NDDD)	NDDD was a measure that represented the average daily maintenance dose for the main indication of a drug.	Up to 12 months after date of first prescription
International Normalized Ratio (INR) Values During the Last 12 Months Values in Participants Previously Treated With VKA	INR was defined as the ratio of the participant's prothrombin time and the normal mean prothrombin time. Prothrombin time defined as a time taken by the blood to clot in participants receiving oral anticoagulant medication. INR was categorized according to the risk level: risk for coagulation (INR<2); optimal range (2<INR<3); and risk of hemorrhages (INR>3).	Up to 12 months after date of first prescription
Time in Therapeutic Range (TTR) Values During the Last 12 Months Values in Participants Previously Treated With VKA	TTR was defined as the duration of time in which the participant's INR values were within a desired range (2 to 3). INR was defined as the ratio of the participant's prothrombin time and the normal mean prothrombin time. Prothrombin time defined as a time taken by the blood to clot in participants receiving oral anticoagulant medication. INR was categorized according to the risk level: risk for coagulation (INR<2); optimal range (2<INR<3); and risk of hemorrhages (INR>3).	Up to 12 months after date of first prescription

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2016
• Primary Completion (Actual): March 8, 2017
• Study Completion (Actual): March 8, 2017

Study Registration Dates

• First Submitted: February 2, 2018
• First Submitted That Met QC Criteria: February 15, 2018
• First Posted (Actual): February 22, 2018

Study Record Updates

• Last Update Posted (Actual): June 9, 2023
• Last Update Submitted That Met QC Criteria: June 7, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: stroke; atrial fibrillation; apixaban
• 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
• Other Study ID Numbers: B0661076; SPAF (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.