High-dose aspirin is required to influence plasma fibrin network structure in patients with type 1 diabetes

Abstract

Objective: Patients with type 1 diabetes form a less permeable fibrin network, which could contribute to their increased risk of cardiovascular disease (CVD). Low-dose aspirin treatment is the standard in the management of CVD; however, the effect seems reduced in patients with diabetes. We investigated the effects of low- and high-dose aspirin treatment on fibrin network formation in patients with type 1 diabetes (primary aim) and the possible interaction between the treatment effects of aspirin on fibrin network permeability and glycemic control in these patients (secondary aim).

Research design and methods: Forty-eight patients (24 subjects with good [HbA(1c) <7.4%] and 24 subjects with poor [HbA(1c) >8.4%] glycemic control) were randomly assigned to treatment with 75 or 320 mg/day aspirin during 4 weeks in a crossover fashion. A 4-week washout period separated the treatment periods. The plasma fibrin network was assessed by determination of the permeability coefficient (K(s)).

Results: Treatment with 75 mg aspirin did not influence fibrin network permeability (K(s)). However, K(s) increased significantly during treatment with 320 mg aspirin (P = 0.004), and a significant treatment effect was seen compared with treatment with 75 mg aspirin (P = 0.009). The increase in K(s) during high-dose aspirin treatment was significant in patients with poor glycemic control (P = 0.02), whereas K(s) only tended to increase in patients with good glycemic control (P = 0.06).

Conclusions: A high dose of aspirin is required to influence fibrin network permeability in patients with type 1 diabetes. The observed lack of effect with low-dose aspirin may contribute to aspirin treatment failure in diabetes.

Trial registration: ClinicalTrials.gov NCT01397513.

Figure 1

Fibrin network permeability coefficient (K_s) during treatment with 75 and 320 mg aspirin. Data are presented as means and 95% CIs (n = 41). K_s increased during treatment with 320 mg aspirin (○), and a significant treatment effect was seen compared with treatment with 75 mg aspirin (●) (P = 0.009).

Figure 2

Fibrin network permeability coefficient (K_s) during treatment with 75 and 320 mg aspirin in patients with good and poor glycemic control, respectively. Data are presented as means and 95% CIs (n = 41). No significant treatment effects were seen in patients with good glycemic control. K_s increased during treatment with 320 mg aspirin (○) in patients with poor glycemic control (P = 0.02), and a significant treatment effect was seen compared with treatment with 75 mg aspirin (●) (P = 0.01).