Statins but not aspirin reduce thrombotic risk assessed by thrombin generation in diabetic patients without cardiovascular events: the RATIONAL trial

PLoS One. 2012;7(3):e32894. doi: 10.1371/journal.pone.0032894. Epub 2012 Mar 28.


Background: The systematic use of aspirin and statins in patients with diabetes and no previous cardiovascular events is controversial. We sought to assess the effects of aspirin and statins on the thrombotic risk assessed by thrombin generation (TG) among patients with type II diabetes mellitus and no previous cardiovascular events.

Methodology/principal findings: Prospective, randomized, open, blinded to events evaluation, controlled, 2×2 factorial clinical trial including 30 patients randomly allocated to aspirin 100 mg/d, atorvastatin 40 mg/d, both or none. Outcome measurements included changes in TG levels after treatment (8 to 10 weeks), assessed by a calibrated automated thrombogram. At baseline all groups had similar clinical and biochemical profiles, including TG levels. There was no interaction between aspirin and atorvastatin. Atorvastatin significantly reduced TG measured as peak TG with saline (85.09±55.34 nmol vs 153.26±75.55 nmol for atorvastatin and control groups, respectively; p = 0.018). On the other hand, aspirin had no effect on TG (121.51±81.83 nmol vs 116.85±67.66 nmol, for aspirin and control groups, respectively; p = 0.716). The effects of treatments on measurements of TG using other agonists were consistent.

Conclusions/significance: While waiting for data from ongoing large clinical randomized trials to definitively outline the role of aspirin in primary prevention, our study shows that among diabetic patients without previous vascular events, statins but not aspirin reduce thrombotic risk assessed by TG.

Trial registration: NCT00793754.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticholesteremic Agents / therapeutic use*
  • Aspirin / therapeutic use*
  • Atorvastatin
  • Cardiovascular Diseases* / complications
  • Cardiovascular Diseases* / prevention & control
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / diagnosis
  • Double-Blind Method
  • Female
  • Fibrinolytic Agents / therapeutic use*
  • Heptanoic Acids / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Pyrroles / therapeutic use*
  • Risk Factors
  • Thrombin / analysis*


  • Anticholesteremic Agents
  • Fibrinolytic Agents
  • Heptanoic Acids
  • Pyrroles
  • Atorvastatin
  • Thrombin
  • Aspirin

Associated data