title: Effect of long-term adherence to clopidogrel on the VASP-PRI after elective coronary stent implantation: a randomized controlled study.
abstract: The biological response to clopidogrel is highly variable and a poor responsiveness is associated with major adverse cardiac events. Adherence to therapy is a major cause of poor responsiveness but its impact on long-term platelet inhibition is unknown. The objective of the present study was to evaluate the effect of different programmes monitoring adherence to clopidogrel on platelet reactivity.
  
  
  
  The study took the form of a monocentric, parallel group, randomized controlled trial. Adults treated with clopidogrel 75 mg after elective coronary stenting were randomized into one of three groups: (i) a standard of care group; (ii) a standard of care + adherence electronic monitoring group, in which drug intake was recorded but kept blinded until the study end; or (iii) an integrated care group, with regular feedback on recorded adherence. Clopidogrel response was assessed with the vasodilator-stimulated phosphoprotein-platelet reactivity index (VASP-PRI) at randomization, 3 months and 6 months.
  
  
  
  A total of 123 adults were enrolled and randomized. Baseline VASP-PRI was highly variable, with a mean of 48 ± 18.8%. No difference between groups in VASP-PRI was found at 6 months (P = 0.761), despite better adherence to clopidogrel in the integrated care group. However, adherence (P = 0.035) and baseline VASP-PRI (P = 0.015) were associated with VASP-PRI at 3 months and 6 months. The association between adherence and VASP-PRI was lost in patients with baseline VASP-PRI > 50%. Diabetes, CYP2C19*2 carrier status and body mass index were significant predictors of VASP-PRI.
  
  
  
  The platelet response to clopidogrel during chronic therapy remained highly variable, despite high adherence. Different adherence monitoring programmes did not affect VASP-PRI at 6 months. Poor adherence is associated with lower VASP-PRI only in initial good responders to clopidogrel.
authors.affiliation: Service of Nephrology and Hypertension, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Valentina
authors.initials: V
authors.lastname: Forni Ogna
authors.affiliation: Service of Nephrology and Hypertension, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Menetrey
authors.affiliation: Department of Cardiology, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Muller
authors.affiliation: Aardex Group, Visé, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Tousset
authors.affiliation: Service of Nephrology and Hypertension, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Linda
authors.initials: L
authors.lastname: Guihard
authors.affiliation: Division of Angiology and Hemostasis, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland.
authors.forename: Pierre
authors.initials: P
authors.lastname: Fontana
authors.affiliation: Department of Cardiology, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Eric
authors.initials: E
authors.lastname: Eeckhout
authors.affiliation: Unit of Biochemistry and Clinical Psychopharmacology, Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Chin B
authors.initials: CB
authors.lastname: Eap
authors.affiliation: Aardex Group, Visé, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Vrijens
authors.affiliation: Service of Nephrology and Hypertension, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Michel
authors.initials: M
authors.lastname: Burnier
authors.affiliation: Service of Nephrology and Hypertension, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Grégoire
authors.initials: G
authors.lastname: Wuerzner
mesh_terms: D000368:Aged; D015815:Cell Adhesion Molecules / Q000097:blood*; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000097:blood*; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention; D010750:Phosphoproteins / Q000097:blood*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D000098662:Vasodilator-Stimulated Phosphoprotein; D016903:Drug Monitoring
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D000098662:Vasodilator-Stimulated Phosphoprotein; D000077144:Clopidogrel; D013988:Ticlopidine
keywords: CYP450 2C19 loss-of-function polymorphism; VASP-PRI; clopidogrel responsiveness; drug adherence; elective coronary stenting