title: Tailored antiplatelet therapy to improve prognosis in patients exhibiting clopidogrel low-response prior to percutaneous coronary intervention for stable angina or non-ST elevation acute coronary syndrome.
abstract: OBJECTIVE
  To investigate whether an intensified antiplatelet regimen could improve prognosis in stable or non-ST elevation in acute coronary syndrome (ACS) patients exhibiting high on-treatment platelet reactivity (HTPR) on clopidogrel and treated with percutaneous coronary intervention (PCI). There is a wide variability in the platelet reactivity to clopidogrel and HTPR has been associated with a poor prognosis.
  
  
  METHODS
  In this observational study, 923 consecutive patients without ST-elevation myocardial infarction (STEMI) and adequately pre-treated with clopidogrel were screened for HTPR with multiple electrode aggregometry after assessment of the coronary anatomy. Patients were grouped based on their response to clopidogrel and the assigned antiplatelet strategy. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, or stent thrombosis.
  
  
  RESULTS
  HTPR was demonstrated in 237 patients (25.7%). Of these, 114 continued on conventional clopidogrel therapy, while the remaining 123 received intensified antiplatelet therapy with either double-dose clopidogrel (150 mg daily, n = 55) or the newer P2Y12-inhibitors, prasugrel or ticagrelor (n = 68) for at least 30 days after the index procedure. The median follow-up was 571 days (interquartile range, 373-746). Intensifying antiplatelet therapy reduced the rate of the composite endpoint (p < 0.001). After adjustment for potential confounders, HTPR in combination with conventional clopidogrel therapy remained independently associated with an increased risk of cardiovascular events (hazard ratio (HR), 2.92; 95% CI, 1.90-4.48), whereas intensified treatment reduced the risk to a level equivalent to that of patients exhibiting normal platelet reactivity (HR, 1.08; 95% CI, 0.59-1.99).
  
  
  CONCLUSIONS
  Tailored antiplatelet therapy significantly reduced the event rate in patients exhibiting HTPR prior to PCI.
authors.affiliation: Department of Cardiology, The Heart Centre , Rigshosptalet , Denmark .
authors.forename: Nadia
authors.initials: N
authors.lastname: Paarup Dridi
authors.forename: Pär I
authors.initials: PI
authors.lastname: Johansson
authors.forename: Jacob T
authors.initials: JT
authors.lastname: Lønborg
authors.forename: Peter
authors.initials: P
authors.lastname: Clemmensen
authors.forename: Maria D
authors.initials: MD
authors.lastname: Radu
authors.forename: Abbas
authors.initials: A
authors.lastname: Qayyum
authors.forename: Frants
authors.initials: F
authors.lastname: Pedersen
authors.forename: Rudi
authors.initials: R
authors.lastname: Kollslid
authors.forename: Steffen
authors.initials: S
authors.lastname: Helqvist
authors.forename: Kari
authors.initials: K
authors.lastname: Saunamäki
authors.forename: Henning
authors.initials: H
authors.lastname: Kelbæk
authors.forename: Erik
authors.initials: E
authors.lastname: Jørgensen
authors.forename: Thomas
authors.initials: T
authors.lastname: Engstrøm
authors.forename: Lene
authors.initials: L
authors.lastname: Holmvang
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D060050:Angina, Stable / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D008297:Male; D062645:Percutaneous Coronary Intervention; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011379:Prognosis; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D013988:Ticlopidine
keywords: Antiplatelet therapy; clopidogrel; ischemic heart disease; prasugrel; prognosis