Marlene Busko

October 02, 2017

LISBON, PORTUGAL — Differences in platelet response to aspirin in blood samples from patients with type 2 diabetes compared with controls hint that the former might benefit from twice-daily, rather than once-a-day, aspirin dosing for primary prevention of cardiovascular events.

However, these findings are from a small early study, and it is not known whether this different dosing would ultimately affect cardiovascular outcomes.

Specifically, in this research involving 42 aspirin-naïve individuals, patients with diabetes had higher levels of platelet aggregation than controls before aspirin therapy was initiated.

Then, after a week of aspirin therapy, patients with diabetes had a higher number of immature platelets — indicating that they had a higher platelet turnover and more newly produced platelets that were not inhibited by aspirin — although the difference was not significant.

Liv Vernstrøm, a master's student in the department of endocrinology and internal medicine at Aarhus University in Denmark, reported these findings in a poster at the European Association for the Study of Diabetes (EASD) 2017 Annual Meeting.

"Given that platelets in people with diabetes are characterized by increased aggregation and increased turnover rates, our study indicates that patients with type 2 diabetes may achieve additional benefit from twice-daily rather than once-daily dosing of aspirin," she and her colleagues comment in an EASD press release.

"We suggest that [patients with type 2 diabetes] might benefit from a more frequent dosing," but "I need to stress that we do not [yet] recommend people with diabetes take aspirin twice a day," Ms Vernstrøm emphasized to Medscape Medical News in an email.

"We have not tested this, and it needs to be evaluated in large-scale clinical outcome trials before any conclusions can be made."

Invited to comment, Dominick J Angiolillo, MD, University of Florida, Jacksonville, told Medscape Medical News in an email that "the data from this study are in line with prior investigations in the field and suggest that a twice-daily [aspirin] regimen may allow for better antiplatelet protection."

However, he too cautioned that "whether these laboratory findings translate into better clinical outcomes remains unknown," and further studies are needed to investigate this.

Aspirin's Antiplatelet Effect in Diabetes

The antiplatelet effect and platelet turnover with aspirin therapy has not been explored in patients with type 2 diabetes who do not have cardiovascular disease, Ms Vernstrøm and colleagues explained.

To investigate this, they measured platelet aggregation and immature platelet count in blood samples from 21 patients with type 2 diabetes and 21 age- and sex-matched controls.

The patients had a mean age of 62, and 67% were male.

Patients with type 2 diabetes had had it for a mean of 9 years and were more likely to be taking antihypertensive drugs (76% vs 33%, = .01) and lipid-lowering drugs (52% vs 5%, < .001) and have a higher heart rate (68 vs 59 beats/min, = .01) than the control individuals. More than one in 10 participants (14%) were current smokers.

At baseline, patients with diabetes had higher levels of platelet aggregation than controls (= .03). An hour after the first dose of aspirin, platelet aggregation was reduced in both groups.

After a week of daily low-dose aspirin, when a steady state of aspirin had been reached, platelet aggregation levels an hour after ingesting aspirin were much lower than they had been after the first aspirin dose in both groups.

Platelet aggregation also increased from 1 hour to 24 hours after patients received aspirin in both groups (indicating a declining antiplatelet effect over this dosing interval).

However, compared with controls, patients with type 2 diabetes had a greater number of immature platelets (indicating a higher platelet turnover), although this was not statistically significant (= .09)

Daily Aspirin for Primary CV Prevention in Diabetes in ACCEPT-D, ASCEND

Results of the ongoing Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes (ACCEPT-D) and A Study of Cardiovascular Events in Diabetes (ASCEND) trials will "hopefully establish whether patients with diabetes benefit from once-daily aspirin dosing" for primary prevention of CVD, Ms Vernstrøm noted.

"If these studies show a net benefit from aspirin treatment, our study indicates that [patients with type 2 diabetes] may achieve additional benefit from an alternate [twice-daily] dosing regimen, which could be interesting to investigate in the future," she added.

"The same phenomenon of a reduced effect of aspirin is also seen in patients with diabetes and known cardiovascular disease, so another approach could be to test the effect of twice-daily dosing in this [secondary-prevention] patient group first," Ms Vernstrøm suggested.

The study was supported by the Danish Council for Independent Research, Aase og Ejnar Danielsens Fond. The authors report no relevant financial relationships.  

European Association for the Study of Diabetes 2017 Annual Meeting; September 13, 2017; Lisbon, Portugal. Poster 1132

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