The use of aspirin therapy for secondary prevention of cardiovascular events has been well established. Nevertheless, there is growing controversy regarding its use for primary prevention; especially in patients with Type 2 diabetes mellitus (T2DM).1,2 The risk of coronary heart disease (CHD) is up to four times greater in a patient with T2DM as compared to someone who is nondiabetic.3 Studies have shown that diabetic patients without recognized cardiovascular disease have demonstrated comparable or increased cardiovascular events and death compared to patients with CHD alone.4 Therefore, diabetes alone has since been considered a CHD risk equivalent. The prior long-standing recommendation to use low-dose aspirin for primary prevention in diabetic individuals was based on indirect evidence extrapolated from large trials of populations at equally high risk.1 However, as new evidence emerges specific to diabetics, organizations that produce consensus guidelines, including the American Diabetic Association, have redefined their recommendations for the use of aspirin for primary prevention.
Recently, the British Medical Journal published a meta-analysis addressing the use of aspirin for primary prevention of cardiovascular events in people with diabetes.1 The meta-analysis included six trials, totaling 10,117 people with diabetes. Five trials were primary prevention trials, and one trial was mixed. The dose of aspirin ranged from 100mg every other day to 650mg daily. The duration of follow-up ranged from 3.6 to 10.1 years. The primary outcomes of interest were all cause mortality, death from cardiovascular causes, non-fatal myocardial infarction, and non-fatal stroke.
The authors included prospective, randomized, controlled, open or blinded trials of participants with diabetes mellitus (Type I, Type II, or both) who were allocated to aspirin treatment or a control group (placebo or no treatment) for the primary prevention of cardiovascular disease. Data on subsets of people with diabetes from larger studies where aspirin was tested against a control group was also included. Six trials were chosen, one of which included a small proportion (<10%) of patients with pre-existing established cardiovascular events. The authors recognized this as a potential limitation.
Appropriate statistical analysis were performed and it was determined that there was no significant risk reduction in regards to the primary outcomes: all cause mortality (4 studies, RR=0.93, 0.82-1.05; P=0.22), major cardiovascular events (5 studies, RR=0.90, 0.81-1.00; P=0.06), myocardial infarction (6 studies, RR=0.86, 0.61-1.21; P=0.37), stroke (5 studies, RR=0.83, 0.60-1.14; P=0.25), and death from cardiovascular causes (4 studies, RR=0.94, 0.72-1.23; P=0.68). Heterogeneity for the later three study outcomes was found to be moderate; reporting quantified inconsistency (I2) values equal to 62.2%, 52.5%, and 56.6% respectively. Evaluation of secondary outcomes found no significant increase in risk of bleeding, gastrointestinal symptoms or cancer.
This meta-analysis could not identify a clear benefit for the use of aspirin in the primary prevention of major cardiovascular events or mortality in people with diabetes. The data, because it considered people with both type 1 and type 2 diabetes together, may be masking a potential benefit that people with type II diabetes may incur with aspirin therapy for primary prevention. Compared to type I diabetes, type II diabetes is late onset and has distinct pathophysiological ...