The study will analyse primary care data to calculate risk of heart attacks, strokes, cancers, and major bleedings, in people with diabetes mellitus in England, and compare them with the risks reported in the Study of Cardiovascular Events in Diabetes (ASCEND).
ASCEND is the largest study of the effect of aspirin and fish oil supplementation on the risk of heart attacks and stroke in people with diabetes mellitus.
Participants for the clinical trial were recruited between 2005 and 2011 by mailed invitation with follow-up information obtained from 6-monthly questionnaires. During the follow-up period, fewer participants developed heart attacks, strokes and cancers, than expected based on reports from previous randomized trials. A number of factors could explain the observed lower rates of diseases: the selection process of participants for the trial might have favoured healthier individuals with diabetes, while less healthier individuals were excluded because they did not meet the study eligibility standards, better compliance with evidence-based therapies within trials, and inappropriate reference populations used to estimate rates of these conditions. Another important factor might be the effect of falling incident vascular disease rates with time in the general population (ie secular trends), which are rarely fully appreciated by researchers when planning trials. We propose to conduct a study using the real-world data on people with diabetes to calculate most up-to-date rates of heart attacks, stroke, cancers, and major bleedings, and compare these with rates reported by the clinical trial.
The findings will inform the interpretation of the ASCEND results, as well as inform the design of future randomized trials.
We propose to conduct a retrospective cohort study using primary care data to compare the risk of cardiovascular events, cancers, and major bleedings, in a cohort of people with diabetes mellitus registered with a primary care physician in England with risks reported in the Study of Cardiovascular Events in Diabetes (ASCEND). ASCEND is the largest clinical trial reporting on the effect of aspirin and fish oil supplementation on the risk of serious cardio- and cerebrovascular events in people with diabetes mellitus, published in the New England Journal of Medicine in October 2018.
Participants for ASCEND were recruited between 2005 and 2011 by mailed invitation with follow-up information obtained from 6-monthly questionnaires. During the 7.5 year follow-up period a lower rate of events of interest was observed than anticipated. Several explanations have been suggested, including selection of healthier individuals, better compliance with evidence-based therapies within trials, and inappropriate reference populations used to estimate event rates. Importantly, a lower event rate can reflect falling of incident vascular event rates in the general population, which is rarely fully appreciated by researchers when planning trials.
We will use the inclusion criteria developed for the ASCEND trial with some modifications for electronic primary care data. In analysis the exposure condition is diabetes mellitus without vascular diseases. Risk of outcomes is calculated using Cox regression model. We will use the same outcomes as in the ASCEND clinical trial; the primary outcome is myocardial infarction, ischaemic stroke or transient ischaemic attack, or death from any vascular cause, excluding intracranial haemorrhage. The secondary outcomes are gastrointestinal tract cancers and major bleedings. We will then compare these rates with the rates reported in the ASCEND study population. A linkage to Hospital Episode Statistics and mortality statistics will provide information on people with diabetes who were admitted to hospital with outcomes of interest, or died from these conditions.
The findings will inform the interpretation of the ASCEND results, as well as inform the design of future randomized trials.
The outcomes are myocardial infarction, ischaemic stroke, transient ischaemic attack, coronary and non-coronary revascularisation procedures, major bleedings and all cancers, excluding non-melanoma skin cancer, documented in the patient clinical or referral record, or death certificate. Coronary revascularisation procedures include coronary angioplasty, stenting or coronary artery bypass grafting. Non-coronary revascularisation include peripheral angioplasty or stenting, atherectomy, thrombectomy, embolectomy, catheter directed thrombolysis, arterial bypass surgery and aneurysm repair. Bleeding events will include gastrointestinal, intracranial and admissions for other bleeding.
Marion Mafham - Chief Investigator - University of Oxford
Eva Morris - Corresponding Applicant - University of Oxford
Aden Kwok - Collaborator - University of Oxford
Alison Offer - Collaborator - University of Oxford
Jane Armitage - Collaborator - University of Oxford
Marion Mafham - Collaborator - University of Oxford
Sarah Parish - Collaborator - University of Oxford
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation