title: Optimizing of thienopyridine therapy by multiple electrode platelet aggregometry in clopidogrel low responders undergoing PCI.
abstract: OBJECTIVE
  One possible cause of stent thrombosis is an insufficient effect of clopidogrel. In a prospective study, we aimed to optimize the platelet inhibition of clopidogrel low responders (CLR) by multiple electrode platelet aggregometry (MEA)-guided therapy modifications and to evaluate specific major adverse cardiac and cerebrovascular events (MACCE).
  
  
  RESULTS
  ADP-induced platelet aggregation was measured by MEA in 1,005 consecutive patients after stent implantation and 600 mg clopidogrel loading dose. All patients received at least 100 mg aspirin/day. In 118 patients (11.7%), ADP values remained in the reference range generated in 150 controls and were defined as CLR. Significant independent predictors of CLR were acute coronary syndrome (ACS) (OR = 6.54), diabetes (OR = 2.07), use of diuretics (OR = 1.93) or proton pump inhibitors (OR = 1.64) and male gender (OR = 1.83). Ninety-nine CLR were switched to clopidogrel 150 mg/day, leading to an adequate response in 54/99. Subsequently, 44 patients were changed to ticlopidine 2 × 250 mg/day, resulting in an inhibition in 24/44. The remaining 20 patients received 2 × 100 mg cilostazol/day in addition to 75 mg clopidogrel/day. After its recent availability, 19/118 primary CLR were treated with 5-10 mg prasugrel/day. One patient was a prasugrel low responder. The total thienopyridine low response-rate was 2% in our population. The specific MACCE rate (death, non-fatal target vessel myocardial infarction, non-fatal stroke) of the CLR under optimized treatment (except prasugrel) was 2.0% at 30 days and 3.0% during a mean follow-up of 44 weeks.
  
  
  CONCLUSIONS
  Clopidogrel low response is present in 1/10 patients and more frequent in ACS-PCI. MEA-guided optimizing of thienopyridine therapy is feasible and results in a very low specific MACCE rate. Low response to all thienopyridines is rare.
authors.affiliation: Medizinische Klinik, Klinikum Augsburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Behr
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kuch
authors.forename: Werner
authors.initials: W
authors.lastname: Behr
authors.forename: Wolfgang
authors.initials: W
authors.lastname: von Scheidt
mesh_terms: D000244:Adenosine Diphosphate; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects* / Q000295:instrumentation; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D002561:Cerebrovascular Disorders / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D000077407:Cilostazol; D000077144:Clopidogrel; D016903:Drug Monitoring / Q000295:instrumentation / Q000379:methods*; D004351:Drug Resistance; D057915:Drug Substitution; D004566:Electrodes; D005260:Female; D005858:Germany; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D016017:Odds Ratio; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010979:Platelet Function Tests / Q000295:instrumentation; D000068799:Prasugrel Hydrochloride; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D015607:Stents; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D013876:Thiophenes; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D000077407:Cilostazol; D013988:Ticlopidine