Aclidinium is used to relieve symptoms in adults with chronic lung disease. A few studies have raised concerns that tiotropium and ipratropium, two drugs similar to aclidinium, may have adverse effects on the heart. Heart disease and death are described as potential risks for aclidinium. The objective of this research is to evaluate, through a series of studies, the potential for heart disease and death with aclidinium use. The first study evaluated the risk of death due to any cause. The second of these studies evaluated the risk of heart failure and the third and fourth, the risk of heart attack and stroke. The present study evaluates the risk of arrhythmias; a change from the normal heartbeat. In this study we will estimate and compare the risk of arrhythmias among patients who start treatment with aclidinium/formoterol combination (aclidinium/formoterol) and other fixed-dose combinations to treat chronic pulmonary obstructive disease (COPD) with the risk among patients who start treatment with a long-acting beta-agonist (LABA), a drug that has not raised concerns on having adverse effects on the heart.
This cohort study aims to evaluate the risk of arrhythmias in patients initiating aclidinium/formoterol and other fixed-dose combinations as compared to patients initiating LABA and in patients initiating other fixed-dose combination COPD treatments as compared to patients initiating aclidinium/formoterol. The study cohort consists in patients aged ≥40 years with COPD initiating aclidinium/formoterol or other fixed-dose combination COPD treatments in the CPRD Aurum in the UK between 2015 and 2021. All cases of arrhythmias will be included in the cohort study. Exposure to study medications will be ascertained through recorded prescriptions in the CPRD Aurum. The outcomes will include: 1) any type of cardiac arrhythmias, 2) atrial fibrillation and 3) serious ventricular arrhythmias. Arrhythmia event and date, and diagnosis for comorbidities of interest, will be defined based on information from the CPRD Aurum and from the inpatient Hospital Episode Statistic (HES) dataset and the Office for National Statistics (ONS). Statistical analysis will include: 1) descriptive statistics of the cohort; 2) cohort analysis to compare risk of arrhythmias associated with the use of aclidinium/formoterol and other fixed-dose combination COPD treatments versus LABA, and the risk associated with fixed-dose combination COPD treatments versus the risk associated with aclidinium/formoterol, including crude and adjusted incidence rates (IRs), incidence rate ratios (IRRs) and 95% CIs ; 3) IRs and IRRs of arrhythmias among patient subgroups of interest, e.g. by age categories; 4) effect of duration (short or long) of use.
Cardiac arrhythmias: Cardiac arrhythmias will be identified through primary discharge codes for arrythmias in Hospital Episode Statistics (HES), with admission date as the date of the event. Death from cardiac arrythmia will be identified through the ICD-10 codes recorded as the main cause of death in Office for National Statistics (ONS) data. The event date will be the date of death. The list of ICD-10 codes for the identification of arrhythmias can be found in Appendix A.
Atrial fibrillation and severe ventricular arrhythmias: Hospitalisation, or deaths due to atrial fibrillation (ICD-10: I48) or for serious ventricular arrhythmia (SVA), i.e., torsade de pointes, ventricular tachycardia, and ventricular fibrillation or flutter (ICD-10: I47.0, I47.2, I49.0), will be identified as follows:
• Hospitalisations due to atrial fibrillation or SVA will be identified by a hospital primary discharge code for atrial fibrillation and SVA in HES, being the date of the event (index date) the admission date.
• Death from atrial fibrillation or SVA will be identified in ONS through ICD-10 codes for atrial fibrillation and SVA recorded as the main cause of death (i.e., in the cause variable), and the date of the event will be the date of death.
CRISTINA REBORDOSA GARCIA - Chief Investigator - RTI Health Solutions ( USA )
Nuria Saigi - Corresponding Applicant - RTI Health Solutions ( USA )
Alejhandra Lei - Collaborator - AstraZeneca Ltd - UK Headquarters
Christine Bui - Collaborator - RTI Health Solutions ( USA )
CRISTINA REBORDOSA GARCIA - Collaborator - RTI Health Solutions ( USA )
Elena Rivero-Ferrer - Collaborator - RTI Health Solutions ( USA )
Jaume Aguado - Collaborator - RTI Health Solutions ( USA )
Jennifer Bartsch - Collaborator - RTI Health Solutions ( USA )
Raquel Garcia Esteban - Collaborator - RTI Health Solutions ( USA )
Sami Daoud - Collaborator - AstraZeneca Ltd - UK Headquarters
Susana Perez-Gutthann - Collaborator - RTI Health Solutions ( USA )
Alejhandra Lei - Collaborator - AstraZeneca Ltd - UK Headquarters
CRISTINA REBORDOSA GARCIA - Collaborator - RTI Health Solutions ( USA )
Michael Stokes - Collaborator - Evidera, Inc
Sami Daoud - Collaborator - AstraZeneca Ltd - UK Headquarters
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation