Abstract
BackgroundDespite the high cardiovascular risk, evidence of efficacy of preventive strategies in individuals with diabetes is scant. In particular, recommendations on the use of aspirin in patients with diabetes mostly reflect an extrapolation from data deriving from other high risk populations. Furthermore, the putative additive effects of aspirin and statins in diabetes remain to be investigated. This aspect is of particular interest in the light of the existing debate regarding the need of multiple interventions to reduce total cardiovascular risk, which has also led to the proposal of a polypill. Aim of the study is to evaluate the efficacy of aspirin in the primary prevention of major cardiovascular events in diabetic patients candidate for treatment with statins. These preventive strategies will be evaluated on the top of the other strategies aimed at optimizing the care of diabetic patients in terms of metabolic control and control of the other cardiovascular risk factors.Methods/DesignThe ACCEPT-D is an open-label trial assessing whether 100 mg/daily of aspirin prevent cardiovascular events in patients without clinically manifest vascular disease and treated with simvastatin (starting dose 20 mg/die). Eligible patients will be randomly assigned to receive aspirin + simvastatin or simvastatin alone. Eligibility criteria: male and female individuals aged >=50 years with diagnosis of type 1 or type 2 diabetes, already on treatment with statins or candidate to start the treatment (LDL-cholesterol >=100 mg/dL persisting after 3 months of dietary advise). The primary combined end-point will include cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospital admission for cardiovascular causes (acute coronary syndrome, transient ischemic attack, not planned revascularization procedures, peripheral vascular disease). A total of 515 first events are needed to detect a reduction in the risk of major cardiovascular events of 25% (alpha = 0.05; 1-beta = 0.90). Overall, 5170 patients will be enrolled. The study will be conducted by diabetes specialists and general practitioners.DiscussionThe study will provide important information regarding the preventive role of aspirin in diabetes when used on the top of the other strategies aimed to control cardiovascular risk factors.Trial registrationCurrent Controlled Trials ISRCTN48110081.
Highlights
Despite the high cardiovascular risk, evidence of efficacy of preventive strategies in individuals with diabetes is scant
It has been shown that diabetic patients without previous myocardial infarction have as high a risk of myocardial infarction as non-diabetic patients with previous myocardial infarction [3]
An analysis on more than 1000 patients with diabetes enrolled in the Primary Prevention Project (PPP) confirmed a non statistically significant reduction of 10% in the incidence of major CV
Summary
Macrovascular complications represent the leading cause of morbidity, mortality, and resource consumption in type 2 diabetes, and their burden is expected to grow in the years due to the increasing incidence of the disease worldwide. In some cases the antiplatelet effects of aspirin can be overwhelmed by aspirin-insensitive mechanisms of platelet activation and thrombus formation, mainly related to an up-regulated vascular inflammatory reaction [8,14] Given these premises, it is of crucial importance to conduct a large-scale, pragmatic trial to evaluate the effectiveness of aspirin use in primary prevention of cardiovascular events in association with statins therapy when included in a strategy of global risk control. It is of crucial importance to conduct a large-scale, pragmatic trial to evaluate the effectiveness of aspirin use in primary prevention of cardiovascular events in association with statins therapy when included in a strategy of global risk control From this point of view, several studies have documented that diabetes is associated with elevated levels of C-reactive protein [15] and endothelial adhesion molecules, considered as markers of the endothelial inflammatory response [16,17].
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