The Role of Omega-3 Fatty Acids and Aspirin in the Prevention of Cardiovascular disease in Diabetes and Biochemical effectiveness of Omega-3 Fatty Acids and Aspirin in the ASCEND trial

Abstract

Abstract: Background The role of aspirin (100 mg daily) and omega-3 fatty acids (FA) (1 g daily) for primary prevention of cardiovascular disease in diabetes is being investigated in the 2x2 factorial design ASCEND trial. To support the interpretation of the trial’s efficacy findings, it is important to compare selfreported compliance by participants with measures of the biochemical effects of each intervention. The previous data on the effect of supplementation with omega-3 FA on coronary heart disease is uncertain. Methods The ASCEND trial randomly allocated 15480 people with diabetes (94% type 2 DM) who do not already have diagnosed occlusive arterial disease to receive aspirin or placebo and to omega-3 FA or placebo. Blood and urine samples were collected by mail at baseline and after 3 years follow-up. The effectiveness of aspirin to suppress urinary thromboxane B2 (UTxB2), a marker of platelet activity, and, of omega-3 FA supplements to increase red cell membrane omega-3 index were assessed. A systematic review of previous trials of omega-3 FA was conducted to summarize the prior evidence for the effects of omega-3 FA supplements on major vascular events (MVEs). Results Aspirin reduced UTxB2 levels by 67% (63-70%) (p <0.0001) compared with placebo, from 3453 pg/mg (95% CI 3061-3895) at baseline to 1190 pg/mg (1100-1287) on those allocated to aspirin during the trial. During follow-up, the omega-3 index increased by 33% (95% CI 26%-39%) in those allocated omega-3 FA compared to placebo (p<0.0001). The meta-analysis of previous studies of omega-3 FA showed no effect on MVEs (HR 0.97; [0.93-1.01]) overall or in any pre-specified sub-groups. Conclusions Low dose aspirin and omega-3 FA are biochemically effective at reducing UTxB2 and increasing the omega-3 index, respectively. Previous trials show that supplementation with omega-3 FA had no significant effect on MVEs. The results of the ASCEND trial, assessing the effects of both aspirin and omega-3 FA on MVEs, will be available in 2018.