People who have had serious medical events that involve their heart and its blood vessels (“cardiovascular”) or their brain and its blood vessels (“cerebrovascular”), in the past are at increased risk of having another of the same or different event. These events, which can be known as “secondary events”, include stroke, unstable angina, heart attack, atrial fibrillation, and also serious bleeding and systemic embolisms.
The size and characteristics of the population in England who are at risk of a second (or more) of these type of events, and the timing of subsequent events, is not well understood. Similarly, relatively little is known concerning the treatments these patients receive to lower the risk of these secondary events.
The project will use the UK Clinical Practice Research Datalink (CPRD) and the Hospital Episode Statistics databases to describe and compare the characteristics of populations in England who are at an increased risk of another event after experiencing one or more events, measure how these patients are treated with common (antiplatelet and anticoagulant) medications and describe the frequency and sequence of events experienced.
Findings from this study will: (1) improve our understanding of the long-term impact of stroke, unstable angina, heart attack, or atrial fibrillation on the likelihood of experiencing another event; (2) help understand how patients are treated; and (3) help assess on whether there is unmet need based on current treatment patterns.
Prevention of thromboembolic events in individuals with atrial fibrillation (AF), acute coronary syndrome (ACS), stroke or transient ischemic attack (TIA) is key to secondary stroke prevention (SSP), prevention of subsequent acute coronary and stroke events in patients with ACS, and stroke prevention in AF (SPAF). Real-world research is needed to quantify the rate of such incident and recurring thromboembolic events (IS/TIA, MI, and major bleeds [MB]) for patients with IS/TIA, ACS, or AF, and adherence to antiplatelet and anticoagulant treatments in these patients.
This retrospective cohort study will use population-level data from England. The Clinical Practice Research Datalink (CPRD) AURUM dataset linked with Hospital Episode Statistics (HES) Admitted Patient Care (APC), and Office for National Statistics (ONS) data will be utilized.
In three cohorts of patients defined according to their diagnoses (IS/TIA, ACS, and AF cohort), this project aims to understand: (1) the patient characteristics, (2) antiplatelet and anticoagulant treatment patterns, (3) the frequency, distribution, and event rates for outcome events of interest, and (4) the differences in demographic and clinical characteristics of patients who experience the outcome events of interest.
Outcomes will be antiplatelet and anticoagulant treatment patterns, and clinical event rates.
For each treatment regimen (including dual antiplatelet therapy), we will describe the number and proportion of patients who experience treatment switch, discontinue treatment, or are persistent on treatment. The Kaplan-Meier (KM) method will be applied to derive the cumulative incidence and empirical distribution of time to each treatment outcome.
Cumulative incidence, mean cumulative count, and event rates (incidence and all-event rates) of clinical outcome events of interest will be calculated. The median time-to-event will be calculated using KM method.
The study findings will benefit patients in England by filling a knowledge gap on treatment patterns and outcomes in individuals with AF, ACS, or stroke or TIA.
The following outcomes will be assessed during the follow-up period for the three cohorts of interest (IS/TIA, ACS, and AF cohort; defined in “Definition of the Study population”):
• Clinical outcomes: Stroke (classified as Ischaemic Stroke [IS] and haemorrhagic stroke) and systemic embolisms; TIA; MI; Major bleed ([MB]; classified as any MB, intracranial MB, and gastrointestinal MB); Major Adverse Limb Events ([MALE]; acute limb ischemia or major vascular [non-traumatic] limb amputation); All-cause and cardiovascular-related mortality
• Treatment patterns: Discontinuation (complete discontinuation, treatment switch, step-down from dual antiplatelet therapy (DAPT) to single antiplatelet therapy (SAPT); Persistence
Treatment patterns will be described for:
• Prescribed antiplatelet treatments: low dose aspirin, hematologic agents, ADP P2Y12 inhibitors, and phosphodiesterase inhibitors
• Prescribed anticoagulant treatments: oral anticoagulants (OACs): Apixaban, Rivaroxaban, Dabigatran, Edoxaban, Warfarin, and low molecular weight heparin (LMWH)
• Baseline characteristics: demographics; clinical characteristics and comorbidities; risk factor scores for AF (HAS-BLED and CHADs-VASc)
Outcomes are fully defined and operationalised below in the “Exposures, Outcomes and Covariates“ section.
Provisional code lists are attached.
Amiee Kang - Chief Investigator - Bristol-Myers Squibb - USA ( BMS )
Marta Kwiatkowska - Corresponding Applicant - Evidera Ltd - UK
Alia Yousif - Collaborator - Evidera, Inc
Alyshah Abdul Sultan - Collaborator - Johnson & Johnson ( JnJ - USA )
Dimitra Lambrelli - Collaborator - Evidera, Inc
Ellen O'Brien - Collaborator - Janssen Global Services LLC
Priyanka Gaitonde - Collaborator - Bristol-Myers Squibb - USA ( BMS )
Robert Donaldson - Collaborator - Evidera Ltd - UK
Sandy Maumus-Robert - Collaborator - Evidera, Inc
Sophie Graham - Collaborator - Evidera, Inc
Valerie Olson - Collaborator - Evidera Ltd - UK
Andrea Lorden - Collaborator - Evidera, Inc
Beth Nordstrom - Collaborator - Evidera, Inc
Nicola Sawalhi-Leckenby - Collaborator - Evidera, Inc
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation