Rationale and background
Existing evidence from case reports and preclinical data raised concerns regarding the proarrhythmic potential of aliskiren, especially with underlying risk of atrial fibrillation. However, little is known about the usage of aliskiren, in particular characteristics of aliskiren users.
This study aims to characterise new aliskiren users to inform the planning and feasibility of a potential future safety study investigating risk of cardiac events.
Research question and objectives
Objectives
The objective of this study is to characterise new aliskiren users to inform the planning of potential future safety studies on aliskiren. The specific objectives are as follows:
1.
To characterise new aliskiren users in terms of demographics, comorbidities, and potential indications for aliskiren use, overall and stratified by age and by sex, during the study period of 2007–2024.
2.
To assess the use of medication, both prior to and after new aliskiren treatment initiation, overall and stratified by age and by sex, during the study period of 2007–2024.
3.
To estimate the number of people with both at least one aliskiren prescription/dispensation record(s) and a record of pre-specified cardiac events anytime during the study period (cross-cohort counts), overall and stratified by age and by sex.
Methods
Study design
Patient-level characterisation
Objective 1 and 2: Patient-level characterisation of new aliskiren users (new drug user cohort)
Population
The study population will include all individuals who received a new aliskiren prescription during the study period 01/01/2007 to 31/12/2024 (or the end of available data), with at least 365 days of database history available prior to the first aliskiren prescription, and with no aliskiren use in the 365 days prior to the “new” aliskiren prescription.
Variables
Exposure: •
Aliskiren
Covariates for characterisation:
•
Demographics: age, sex (Objective 1)
•
Comorbidities: cardiac arrhythmia, cardiomyopathy, heart failure, ischemic heart disease, myocardial infarction, stroke, venous thromboembolism, anxiety, chronic kidney disease, chronic liver disease, dementia, depressive disorder, diabetes, hyperthyroidism, hypothyroidism, malignant neoplastic disease (Objective 1)
•
Indication: hypertension (Objective 1)
•
Medication: agents acting on the renin-angiotensin system (excluding aliskiren), beta blocking agents (systemic), calcium channel blockers, diuretics, other antihypertensive agents, antiarrhythmic agents, antithrombotic agents, digoxin, ivabradine, acetylcholinesterase inhibitor, antibacterials for systemic use, antifungals for systemic use, antidepressants, antiemetics, antimalarial agents, antineoplastic agents, opioids, psycholeptics, psychostimulants (Objective 2)
Covariates for stratification:
•
Age groups
•
Below 18 years
•
18–64 years
•
65 years and above
•
Sex
Statistical analysis
Patient level characteristics of new aliskiren users, including demographics, comorbidities, medication, and potential indication for aliskiren treatment will be reported as counts and proportions. The statistical analyses will be performed based on OMOP CDM mapped data using CohortCharacteristics. A minimum cell counts of 5 will be used when reporting results, with any smaller count reported as “<5”.
Objective 3: Patient-level characterisation of first-time aliskiren users (new drug user cohort, first-time user)
Population
The study population will include all individuals, who received a new aliskiren prescription during the study period 01/01/2007 to 31/12/2024 (or the end of available data), with at least 365 days of database history available prior to the first aliskiren prescription, and without any prior exposure of aliskiren.
Variables
Exposure:
• Aliskiren
Covariate for characterisation:
• Cardiac events, as a composite of
Atrial fibrillation
Atrial arrhythmia other than atrial fibrillation
Ventricular arrhythmias
Sudden cardiac death
• Cardiac arrhythmia • Atrial fibrillation
• Atrial arrhythmia other than atrial fibrillation
• Ventricular arrhythmias
• Sudden cardiac death
Covariates for stratification:
• Age groups
• Below 18 years
• 18–64 years
• 65 years and above
• Sex
Statistical analysis
The number of persons with both first-time aliskiren use and with cardiac events any time before/after aliskiren treatment will be reported (person counts). The statistical analyses will be performed based on OMOP CDM mapped data using CohortCharacteristics. A minimum cell counts of 5 will be used when reporting results, with any smaller count reported as “<5”.
Data sources
1. Denmark: Danish Data Health Registries (DK-DHR)
2. Spain: The Information System for Research on Primary Care (SIDIAP)
3. United Kingdom: Clinical Practice Research Datalink GOLD (CPRD GOLD)
Study size
No sample size has been calculated, as this is an exploratory study which will not test a specific hypothesis. Based on a preliminary feasibility assessment, the expected number of persons counts for aliskiren in the databases included in this study range from 2,300 (CPRD GOLD) to 11,000 (SIDIAP).