Biological Efficacy of Twice Daily Aspirin

Biological efficacy of twice daily aspirin in type 2 diabetic patients with coronary artery disease Jean-Guillaume Dillinger, MD, a,c Akram Drissa, MD, a,c Georgios Sideris, MD, a Claire Bal dit Sollier, PhD, b Sebastian Voicu, MD, a Stephane Manzo Silberman, MD, a Damien Logeart, MD, a Ludovic Drouet, MD, PhD, b and Patrick Henry, MD, PhD a Paris, France

Biological efficacy of twice daily aspirin in type 2diabetic patients with coronary artery disease

Jean-Guillaume Dillinger, MD, a,c Akram Drissa, MD, a,c Georgios Sideris, MD, a Claire Bal dit Sollier, PhD, bSebastian Voicu, MD, a Stephane Manzo Silberman, MD, a Damien Logeart, MD, a Ludovic Drouet, MD, PhD, band Patrick Henry, MD, PhD a Paris, FranceFirmanHakim AlkatiriCARDIOLOGY AND VASCULAR DEPARTMENT MEDICAL FACULTY OF HASANUDDIN UNIVERSITY 2012

BackgroundCardiovascular disease (CVD) remains the leading cause of morbimortality in patients with type 2 diabetes mellitus (DM).

Guidelines recommend low dose of aspirin in secondary prevention of CVD in patients with DM to decrease the rate of cardiovascular events.Diabetes is associated with a high rate of events after acute coronary syndrome and percutaneous coronary intervention despite aspirin treatment.

Once daily aspirin might not provide 24-hour stable biological efficacy in patients with diabetes.AimTo compare the biological efficacy of the same daily dose of aspirin given either once (OPD) or divided twice per day in a population of selected diabetic patients with coronary artery disease (CAD)MethodsSingle-center, crossover study enrolled all consecutive stable patients with DM presenting to the Department of Cardiology, Lariboisiere Hospital, between September 2010 and March 2011.InclusionDM and documented CAD and had been treated for at least 7 days with a nonenteric-coated aspirin.

Population with a higher risk of ALE (Aspirin lack of efficacy) DM with at least one of the following defined from previous study: - Current smoking, - Hs-CRP > 4 mg/L,- Fibrinogen > 4 g/L,- Platelet count > 270 103/mm3.

ExclusionPercutaneous coronary intervention or ACS occurring within the month before.DesignStudy end pointsTo determine whether the same daily dose of aspirin given twice per day was more effective than a single intake on the specific pharmacodynamic effect of aspirin on platelets as assessed by light transmission aggregometry triggered by arachidonic acid (AA) (LTA-AA) 0.5 mg/mL.

The secondary end point of the study was the proportion of patients with high platelet global reactivity while on aspirin either OPD or twice per day as measured by a test evaluating global platelet reactivity, that is, the Platelet Function Analyzer-100 (PFA-100) with collagenepinephrine (EPI) cartridge and adenosine diphosphate (ADP) cartridge.RESULT

Of the criteria qualifying patients as being at high risk of ALE, - 27% of patients were current smokers, - 46% had an hs-CRP >4 mg/L, - 38% had fibrinogen >4 g/L, and - 36% a platelet count >270 103/mm3. - 30% had 2 of these criteria; 15%, 3; and 7%, four.

The PFA-100 was performed to evaluate global reactivity on collagen membrane of platelet sensitized with EPI and ADP depending on the cartridge

DiscussionClinical and biological aspirin resistanceAspirin resistance can be diagnosed clinically by the occurrence of an atherothrombotic ischemic event in a patient taking a therapeutic dose of aspirin.

The incidence of patients not achieving an adequate antiplatelet effect from aspirin varies greatly from one report to another ranging from 5% to 45%.Possible mechanisms of ALESeveral mechanisms have been put forward to explain aspirin resistance or low responsiveness Which is one of the major cause of resistance in daily clinical practice deficient aspirin absorption, and metabolism drug interactions (as with proton pump inhibitors or nonsteroidal anti-inflammatory drugs).

Di Minno et al. demonstrated in a small population that dose schedules of aspirin are not effective in patients with diabetic angiopathy probably because these patients have a high rate of entry of new platelets in the circulation.Di Minno et al In normal conditions, approximately 10% to 15% of circulating platelets are replaced daily, and near normal aggregation due to nonacetylated platelet replacement has been found 48 to 72 hours after last aspirin intake.

The recovery could be reached in