Study Suggests Aspirin, Other Anticoagulants Have Protective Effect Against Diabetic Retinopathy

Patients with diabetes who take aspirin or dipyridamole have a lower risk of developing nonproliferative diabetic retinopathy (NPDR), according to a new study published in BMC Ophthalmology. The investigators aimed to investigate the use of antiplatelet/anticoagulant (APAC) therapy as a potential method of preventing the progression of DR.

The aim of this study was to investigate whether APAC therapy could protect patients with type 2 diabetes (T2D) from the development or progression of DR, including NPDR, proliferate DR (PDR), and diabetic macular edema (DME). The study authors hypothesized that a hypercoagulative state could induce endothelial damage and predispose patients to vascular occlusion.

For this retrospective study, the Longitudinal Health Insurance Database in Taiwan was used to collect data on patients from January 1, 2000, to December 31, 2010. Participants in this study were 20 years and older and had newly diagnosed T2D. Definitions of diagnoses were based on the International Classification of Diseases, Ninth Revision, Clinical Modification.

Patients were excluded from this study if they had a history of NPDR, PDR, panretinal photocoagulation treatment, DME, or intravitreous injection treatment before diagnosis of T2D. Separate groups were created of APAC users (patients with T2D who were on APAC therapy for 28 days or more) and APAC nonusers (patients with T2D not on APAC therapy).

All patients were followed from index date until diagnosis of NPDR, PDR, or DME; withdrawal from the program; or until December 31, 2011. Comorbidities, such as hypertension, dyslipidemia, diabetic nephropathy, heart disease, and cardiovascular disease, were collected from the database, as was medication use.

Differences in categorical data were analyzed with the χ² test. The incidence densities of NPDR, PDR, and DME were calculated as the number of events divided by total person-years. The effect of the APAC drug might have been overestimated if some patients did not take APAC regularly throughout the study period, so the investigators included APAC use as a time-dependent covariate in a Cox proportional hazards model.

From this study, the researchers found that APAC users were older than nonusers (mean [SD] age, 58.6 vs 56.8 years, respectively). The proportions of male participants in the groups of APAC users and nonusers were 53.2% and 51.0%, respectively. Patients with hypertension, dyslipidemia, diabetic nephropathy, diabetic neuropathy, heart disease, cardiovascular disease, and peripheral arteriolar disease made up a higher proportion of APAC users than nonusers.

The mean follow-up periods were 7.33 and 5.51 years for APAC users and nonusers respectively. The incidence of NPDR was lower in APAC users than nonusers (10.7 vs 14.4 per 1000 person-years). APAC users also had a lower risk of NPDR than nonusers (adjusted HR [aHR], 0.78; 95% CI, 0.73-0.83).

The aHR of NPDR was 1.01 (95% CI, 1.01-1.02) for each additional year of age. There was a greater risk of developing NPDR if patients had hypertension (aHR, 1.17; 95% CI, 1.09-1.24), diabetic nephropathy (aHR, 1.26; 95% CI, 1.17-1.36), or diabetic neuropathy (aHR, 1.56; 95% CI, 1.34-1.81). Risk of NPDR was lower in statin users than in nonusers, with an aHR of 0.74 (95% CI, 0.70-0.78).

When taken as monotherapy, both aspirin and dipyridamole showed protection against NPDR development (dipyridamole: aHR, 0.85; 95% CI, 0.74-0.97). Clopidogrel, ticlopidine, warfarin, and dipyridamole reduced the risk of NPDR development when combined with aspirin (aspirin with clopidogrel: aHR, 0.57; 95% CI, 0.44-0.74; aspirin with ticlopidine: aHR, 0.59; 95% CI, 0.39-0.90; aspirin with warfarin: aHR, 0.59; 95% CI, 0.35-0.98; aspirin with dipyridamole: aHR, 0.61; 95% CI, 0.51-0.73).

Despite these associations between APAC use and lower risk of NPDR development, the risks of PDR and DME were not significantly different between those who used APACs and those who did not.

There were some limitations to this study. Because it was a retrospective study, clinical measurements, such as blood pressure and blood sugar control, could not be collected from the database. Patients with APAC use of more than 28 days were included, which, compared with the long duration of follow-up to 12 years, was relatively short. The dosage effect from different APACs was not analyzed in the study. The investigators also noted that the precise duration of hyperglycemia is difficult to track in patients with T2D.

The researchers concluded that APACs were protective against NDPR development in patients with diabetes. Further investigation is needed to identify the effect of these drugs on PDR and DME development and progression.

Reference

Jeng CJ, Hsieh YT, Lin CL, Wang IJ. Effect of anticoagulant/antiplatelet therapy on the development and progression of diabetic retinopathy. BMC Ophthalmol. 2022;22:127. doi:10.1186/s12886-022-02323-z