Aspirin for primary prevention of cardiovascular disease events in diabetes: the balancing act?

Diabetes is the fifth leading cause of death in the world, accounting for approximately 3 million deaths annually. 1 Excess mortality in diabetes is largely due to atherosclerotic cardiovascular disease (ASCVD) and renal complications of diabetes. ASCVD encompassing coronary artery disease, peripheral vascular disease and stroke, occurs much more frequently in diabetic than in nondiabetic males and females, but cardiovascular deaths are greater in females. 2 The high prevalence of ASCVD in persons with diabetes is well documented in many populations of the world. 3 Individuals with diabetes have higher atheroma volume, more atherosclerotic plaque and much narrower coronary lumen than do nondiabetics. 4 This makes them at great risk for a much worse myocardial infarction and occurrence of silent myocardial infarction; however, the concept of diabetes as a risk equivalent for established coronary artery disease is still not universally accepted. 5 Efforts to prevent cardiovascular disease in patients with diabetes is a prime requirement to improve the quality of a patient's life and to prevent deaths. Prevention of ASCVD in patients with diabetes involves a multipronged approach, namely control of hyperglycaemia, statin therapy for dyslipidaemia, treatment of high blood pressure and, of course, antiplatelet therapy, especially after a patient has survived a major event such as acute myocardial infarction or stroke. 6 Although secondary prevention of ASCVD with aspirin is well established, the role of aspirin in primary prevention of ASCVD in patients with diabetes is less well established. In the ASCEND (A Study of Cardiovascular Events in Patients with Diabetes) study investigators randomised >15,000 adults who had diabetes but no evident cardiovascular disease to receive 100 mg aspirin or placebo. 7 The primary outcome was the first serious vascular event (i.e. myocardial infarction, stroke or transient ischemic attack, or death from any vascular cause, excluding any confirmed intracranial haemorrhage). The primary safety outcome was the first major bleeding event, either intracranial haemorrhage, sight-threatening bleeding event in the eye, gastrointestinal bleeding or other serious bleeding. Secondary outcomes included gastrointestinal tract cancer. After a mean follow up of 7.4 years, the primary outcome (i.e. serious vascular event) occurred in a lower proportion of those who received aspirin with a rate ratio of 0.88 (95% confidence interval: 0.79-0.97). This means that usage of aspirin resulted in 12% lower risk of a serious cardiovascular event; however, there was a 28% higher risk of participants experiencing major bleeding. A total of 314 (4.1%) participants in the aspirin group experienced major bleeding compared to 245 (3.2%) in the placebo group. Major bleeding was gastrointestinal in 41.3%, ocular in 21.1%, intracranial in 17.2% and 20.4% in other sites. Of note, the incidence of fatal bleeding was similar in both the groups; 19 vs 16 participants in the aspirin and placebo groups, respectively. The incidence of gastrointestinal cancer was similar in the two groups. © 2018, Royal College of Physicians of Edinburgh. All rights reserved.