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. The present study evaluates the risk of AMI and stroke. In this study we will estimate and compare the risk of AMI and stroke among patients who start treatment with aclidinium and other medications to treat chronic pulmonary obstructive disease (COPD) with the risk among patients who start treatment with LABA, a drug that has not raised concerns on having adverse effects on the heart.
This cohort study aims to evaluate the risk of hospitalisation for AMI and stroke in patients initiating aclidinium and other study medications as compared to patients initiating LABA and in patients initiating other COPD medications as compared to patients initiating aclidinium. The study cohort consists in patients aged ?40 years with COPD initiating aclidinium or other COPD medications in the CPRD Aurum in the UK between 2012 and 2019. All confirmed cases of hospitalisation for AMI and stroke will be included in the cohort study. Exposure to study medications will be ascertained through recorded prescriptions in the CPRD Aurum. The outcomes AMI and stroke will include out-of-hospital coronary heart disease (CHD) death (CHD) and cerebrovascular disease (CeVD) death, respectively. AMI and stroke events 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 AMI and stroke associated with the use of aclidinium and other COPD medications versus LABA, and the risk associated with other COPD medications versus the risk associated with aclidinium: Crude and adjusted RRs and 95% CIs will be estimated for each potential confounding and risk factor; 3) Patient subgroup analyses (stratified by subgroups of interest): risk ratios (crude and adjusted) will be estimated among current users of each study medication; 4) effect of duration (short or long) will be estimated among current users of each study medication.
The following outcomes will be measured:
? Hospitalisation for acute myocardial infarction, either non-fatal or fatal, plus community (out-of-hospital) coronary heart disease deaths
? Acute stroke, either non-fatal or fatal, including community (out-of-hospital) cerebrovascular disease deaths
We propose to use standard clinical definitions similar to those that have been used in prior studies [1-4]:
? An AMI is defined by the evidence of myocardial necrosis in a clinical setting consistent with myocardial ischaemia, including ST elevation myocardial infarction and non–ST elevation myocardial infarction. Because one-third of the patients suffering an AMI die suddenly before arriving at the hospital, community CHD deaths are also included in the definition of AMI. Community death from CHD will be defined as sudden cardiac death or fatal myocardial infarction deaths in persons outside a hospital setting.
? An acute stroke is defined as the rapid onset of a persistent neurological deficit attributed to an obstruction or rupture of the arterial system supplying the brain. Because some patients having a stroke will die before arriving at a hospital facility, community deaths from CeVD will be ascertained.
Ascertainment of the study outcomes in CPRD is described in Section N.
CRISTINA REBORDOSA GARCIA - Chief Investigator - RTI Health Solutions ( USA )
CRISTINA REBORDOSA GARCIA - Corresponding Applicant - RTI Health Solutions ( USA )
Alejhandra Lei - Collaborator - AstraZeneca Ltd - UK Headquarters
Annalisa Rubino - Collaborator - Evidera, Inc
Christine Bui - Collaborator - RTI Health Solutions ( USA )
David Martinez - Collaborator - RTI Health Solutions ( USA )
Elena Rivero-Ferrer - Collaborator - RTI Health Solutions ( USA )
Estel Plana Hortoneda - Collaborator - RTI Health Solutions ( USA )
Hana Mullerova - Collaborator - AstraZeneca Ltd - UK Headquarters
Joan Forns Guzman - Collaborator - RTI Health Solutions ( USA )
Nuria Saigi - Collaborator - RTI Health Solutions ( USA )
Sami Daoud - Collaborator - AstraZeneca Ltd - UK Headquarters
Susana Perez-Gutthann - Collaborator - RTI Health Solutions ( USA )
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation