Aspirin as antiplatelet agent in diabetes: Cons

Abstract

Diabetes, and particularly type 2 diabetes, is becoming a global epidemic. Approximately 180 million people are affected worldwide and as many as 300 millions are expected to be affected in 2025 [1]. Dietary errors, little physical activity, obesity and the metabolic syndrome are the main causes of this epidemic. In men with type 2 diabetes the risk of cardiovascular disease is increased 2 to 3 times [2]. Diabetes has a disproportionate impact on woman health, with a risk of cardiovascular events that is much higher than that of men (a 5to 7-fold absolute increase) [3]. Even though macrovascular disease is due to the early occurrence of atherosclerosis with great severity and diffuse distribution, the ultimate mechanism in the development of cardiovascular events (myocardial infarction, ischemic stroke and peripheral arterial disease) is the formation of occlusive thrombi on vulnerable atherosclerotic plaques. Accordingly, antithrombotic drugs have been widely employed for primary prevention in at-risk people with type 2 diabetes. Among these drugs, antiplatelet agents are those most frequently used, whereas there is a paucity of data on other drugs such as vitamin-K antagonists and heparins. In 1998 the American Diabetes Association (ADA) recommended, in people with diabetes older than 40who had one ormore cardiovascular risk factor, primary prophylaxis with aspirin, i.e., the oldest, cheapest and most widely used antiplatelet agent [4]. This recommendation was jointly reiterated in 2007 by ADA and the American Heart Association (AHA), that identified as additional risk factors prompting primary prevention with aspirin a family history of cardiovascular events, hypertension, smoking, dyslipidemia and microalbuminuria [5]. Pertaining to aspirin dosages, ADA and AHA recommended 75 to 162 mg/day [5]. Unfortunately, there is more and more evidence that, in spite of the forementioned recommendations of ADA and AHA, the efficacy of aspirin in the primary prevention of cardiovascular events in type 2 diabetes is much smaller than that exerted in non-diabetic people. The guidelines recommending aspirin for primary prevention in diabetes were primarily extrapolated from the results obtained in the frame of trials carried out in people enrolled for being at high risk of cardiovascular disease, with very few studies exclusively and purposely carried out in diabetics. The first evidence of the limited efficacy of antiplatelet therapy with aspirin in the frame of primary prevention stems for the 2002 meta-analysis of the Antithrombotic Trialists' Collaboration (287 trials, 135.000 participants) [6]. The relative reduction of major cardiovascular events in the subgroup of diabetics (5126 participants) was only 7%, much less than that observed in other asymptomatic people at risk of cardiovascular events (22%). Another caveat on the limited efficacy of aspirin in diabetes was subsequently provided by the Primary Prevention Project, carried out in 4500 people aged 50 or more who had no overt cardiovascular disease but at least one risk factor [7]. According