• Thrombin generation [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  

• C-reactive protein [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  

Despite the very high cardiovascular risk profile, evidence of efficacy of aspirin in individuals with diabetes is scant.

The meta-analysis on the efficacy of antiplatelet therapy involving a total of about 5,000 diabetic subjects indicates a non significant reduction in the risk of major cardiovascular events of 7%, compared with a reduction of 25% documented in secondary prevention studies.

Diabetes could represent a special case of aspirin resistance, although no specific studies have, to our knowledge, fully explored this hypothesis. The poor platelet responsiveness to aspirin has been recently proposed as a possible explanation of the failure of antiplatelet therapy to prevent cardiovascular events. The reduction in the aspirin activity in some patients is indicated by the failure in adequately suppressing thromboxane-A2 synthesis, as documented by the presence of high levels of its urinary metabolites.

The substantial lack of clear evidence is reflected by the low use of this drug in clinical practice; in fact, only 10% of diabetic patients are treated with aspirin for the prevention of cardiovascular events.

On the other hand, statins provide a similar efficacy for the prevention of major cardiovascular events in populations with and without diabetes.

It has been recently shown that platelet response to aspirin is linearly reduced with increasing cholesterol plasma levels. The presence of dyslipidemia, particularly common among diabetic patients, could thus be at least partially responsible for a lower efficacy of aspirin in this population. The concomitant use of statins could thus restore the normal platelet sensitivity to aspirin by reducing cholesterol levels

One additional reason to hypothesize a positive effect of statins in improving platelet response to aspirin is related to their anti-inflammatory properties

While the efficacy of aspirin versus placebo in patients with diabetes is currently under investigation, the additive effects of aspirin and statins in this population 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.

Given these premises, it is important 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.

The RATIONAL Study will evaluate wether the combined use of aspirin (100 mg d) and statins (Rosuvastatin 10 mg dayly) is superior to the use of these single agents for the reduction of thrombin generation in patients with diabetes and without previous cardiovascular events.