A recent study published in Ophthalmology evaluated the relationship between diabetic retinopathy (DR) and aspirin in a follow-up to the ASCEND-Eye trial.
Give me some background first.
With DR being a leading contributor to visual impairment, previous research has found that the antithrombotic and anti-inflammatory effects of aspirin “may modify this disease process.
With only two existing trials on DR outcomes from aspirin, researchers decided to investigate randomized trials to assess the efficacy of aspirin regarding DR.
What else do we know?
In the 1991 Early Treatment Diabetic Retinopathy Study (ETDRS), participants received 650 mg of aspirin a day for 7 years.
While there were no preventative effects found on the development of high-risk proliferative features in people with established DR, early development wasn’t investigated.
And in the 1989 Dipyridamole Aspirin Microangiopathy of Diabetes (DAMAD) study, those who took 990 mg of aspirin a day had marginally fewer microaneurysms per year than those in the placebo group.
However, long-term significance was uncertain and eye-bleeding events were not reported.
Now, talk about the study.
This most recent research was a sub-study of the double-blind and placebo-controlled ASCEND (A Study of Cardiovascular Events iN Diabetes) trial.
Conducted between 2011 and 2017, the study was intended to compare the use of 100 mg daily aspirin in patients with diabetes and the prevention of serious cardiovascular events.
Who was included in ASCEND?
The participants had the following characteristics:
- Type I or type II diabetes
- At least 40 years of age
- No previous history of cardiovascular disease
- No contraindication to the use of aspirin
- No pre-existing life-limiting medical condition
What information was collected?
After participants were randomized, each was assigned to either placebo or active aspirin groups (see the full flow of assigned participants here).
They were then sent follow-up questionnaires every 6 months, which sought information about the trial’s main endpoints, adverse events, and adherence to the study treatments.
Now about this sub-study…
In the ASCEND-Eye sub-study, randomized participants were linked to their national retinopathy screening records and information was obtained from primary care providers to more closely examine the effect of aspirin on DR.
After exclusion criteria and lost follow-up, a total of 7,360 patients from ASCEND were included in ASCEND-Eye, and thus within the efficacy analysis on DR.
What were the efficacy analysis outcome measures?
Researchers evaluated the following measures:
- First post-randomization record of referable disease (a composite of referable retinopathy (R2 or R3a/s) or referable maculopathy (M1))
- First sight-threatening eye bleed
- First post-randomization occurrence of referable disease in those without retinopathy
- Progression in retinopathy grade stratified by duplex retinopathy grades at baseline
Findings?
After a mean follow-up of 6.5 years, 14.2% of participants in the placebo group had a referable disease event, compared to 14.6% in the active group (100 mg aspirin daily).
Aspirin also had no significant effects on progression in retinopathy grade (44.0% in the active group and 43.6% in placebo).
Tell me more.
Additionally, first sight-threatening eye bleed occurred in 0.7% of the active group and 0.8% of the placebo, displaying yet another comparable result.
Expert opinion?
Per the authors of the study, “aspirin had no significant effects on any of the secondary or tertiary outcomes comparing referable disease stratified by baseline DR severity, progression in retinopathy grade, incident diabetic maculopathy, or duplex retinopathy grades at the final eye screening record.”
Go on…
They continued: “Given the large size and long follow-up durations in both ASCEND-Eye and ETDRS, it seems more likely that aspirin does not have measurable beneficial effects in DR or diabetic maculopathy.”
Limitations?
A key limitation to this sub-study is that linkage data was only obtained from around half of the ASCEND participants.
The authors suggested that, while there was no evidence of introduced bias, statistical power would have been higher with double the participants.
They also noted a possible lack of generalizability due to limited ethnic diversity in the ASCEND trial population.
Take home.
As the largest randomized trial of aspirin on DR to date, the ASCEND-Eye sub-study displayed the feasibility of using screening data to help define outcomes.