The effect of sarpogrelate compared to aspirin in high- or very-high-risk diabetes for primary prevention

Abstract

The benefit of aspirin in primary prevention for atherosclerotic cardiovascular diseases (ASCVD) is questionable due to bleeding complications. We analyzed the Korean National Health Insurance data to compare the efficacy and overall bleeding of sarpogrelate, an antiplatelet agent with lower bleeding risk, versus aspirin in high-/very-high-risk diabetic populations without prior ASCVD. The primary endpoint was net adverse clinical events (NACE), defined as a composite of efficacy and overall bleeding. The efficacy was a composite of all-cause death, myocardial infarction (MI) and stroke, whereas overall bleeding included intracranial hemorrhage (ICH) and gastrointestinal (GI) bleeding. A total of 10,778 high-/very-high-risk diabetic patients (9550 on aspirin, 1228 on sarpogrelate) were analyzed. After propensity score matching, sarpogrelate was linked to a lower incidence of NACE (HR:0.71; 95% CI 0.57-0.88), mainly driven by 62% reductions in overall bleeding (0.38; 0.17-0.81), a composite of 64% and 72% lower rate of GI bleeding and ICH, respectively. Additionally, there was no significant differences in MI or stroke between groups. In high- or very-high-risk diabetic patients without ASCVD, sarpogrelate use was associated with net clinical benefit mainly due to the reduction of significant reduction in overall bleeding events.

Keywords: Aspirin; Bleeding; Diabetes; Primary prevention; Sarpogrelate, antiplatelet therapy.

Fig. 1

Flow diagram for selection of study participants. NHIS-NSC, National Health Insurance System – National Sample Cohort; DM, diabetes mellitus; SHIELD, Sarpogrelate Health Intervention for Early Lowering of cardiovascular risk in Diabetes; GI, gastrointestinal.

Fig. 2

Kaplan–Meier survival plots of event free survival for post-matched analyses. Post-matched analysis of aspirin versus sarpogrelate on NACE (A), efficacy endpoint (B), GI bleeding (C), and ICH (D). Matched, propensity score matched; NACE, net adverse clinical events; GI, gastrointestinal; ICH, intracranial hemorrhage.

Fig. 3

Subgroup analysis for NACE. NACE, net adverse clinical events; BMI, body mass index; DM, diabetes mellitus; LDL, low-density lipoprotein; HR_adj, adjusted hazard ratio; CI, confidence interval. * Adjusted for age, sex, insulin therapy, HTN, DM duration, income, smoking status, BMI, statin therapy, LDL, HDL, TG, creatinine, and hemoglobin.

Fig. 4

A summary of study. SHIELD, Sarpogrelate Health Intervention for Early Lowering of cardiovascular risk in Diabetes; NHIS, national health insurance system; NACE, net adverse clinical events; GI, gastrointestinal; ICH, intracranial hemorrhage; ASCVD, atherosclerotic cardiovascular events.