title: Vascular risk levels affect the predictive value of platelet reactivity for the occurrence of MACE in patients on clopidogrel. Systematic review and meta-analysis of individual patient data.
abstract: Prior studies have shown an association between high on-clopidogrel platelet reactivity (PR) and the risk of major adverse cardiovascular events (MACE). However, large intervention trials on PR-tailored treatments have been neutral. The role and usefulness of PR with regard to levels of cardiovascular risk are unclear. We undertook a systematic review and meta-analysis of individual patient data on MACE outcomes (acute coronary syndromes (ACS), ischaemic strokes, and vascular deaths) in relation to PR and its interaction with cardiovascular risk levels. PR was determined using ADP-induced light transmission aggregometry with a primary concentration of 20 µM ADP. Thirteen prospective studies totaled 6,478 clopidogrel-treated patients who experienced 421 MACE (6.5 %) during a median follow-up of 12 months. The strength of the association between the risk of MACE and PR increased significantly (p=0.04) with the number of risk factors present (age> 75 years, ACS at inclusion, diabetes, and hypertension). No association was detected in patients with no risk factor (p=0.48). In patients presenting one risk factor, only high-PR was associated with an increased risk of MACE (HR 3.2, p=0.001). In patients presenting ≥ 2 risk factors, the increase of risk started from medium-PR (medium-PR: HR=2.9, p=0.0004; high-PR: HR=3.7, p=0.0003). PR allowed the reclassification of 44 % of the total population to a different risk level for the outcome of MACE, mostly in intermediate or high risk patients. In conclusion, the magnitude of the association between PR and MACE risk is strongly dependent on the level of cardiovascular risk faced by patients on clopidogrel.
authors.affiliation: Jean-Luc Reny, Division of Internal Medicine and Rehabilitation, Trois-Chêne Hospital, Geneva University Hospitals, Ch. du Pont-Bochet 3, CH-1226 Thônex-Geneva, Switzerland, Tel.: +41 22 305 65 37, Fax: +41 22 305 61 15, E-mail: jean-luc.reny@hcuge.ch.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Reny
authors.forename: Pierre
authors.initials: P
authors.lastname: Fontana
authors.forename: Willibald
authors.initials: W
authors.lastname: Hochholzer
authors.forename: Franz Josef
authors.initials: FJ
authors.lastname: Neumann
authors.forename: Jurriën
authors.initials: J
authors.lastname: Ten Berg
authors.forename: Paul W
authors.initials: PW
authors.lastname: Janssen
authors.forename: Tobias
authors.initials: T
authors.lastname: Geisler
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
authors.forename: Rossella
authors.initials: R
authors.lastname: Marcucci
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Gori
authors.forename: Thomas
authors.initials: T
authors.lastname: Cuisset
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Alessi
authors.forename: Philippe
authors.initials: P
authors.lastname: Berdagué
authors.forename: Paul A
authors.initials: PA
authors.lastname: Gurbel
authors.forename: Gerald
authors.initials: G
authors.lastname: Yong
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
authors.forename: Dániel
authors.initials: D
authors.lastname: Aradi
authors.forename: Roy
authors.initials: R
authors.lastname: Beigel
authors.forename: Gianluca
authors.initials: G
authors.lastname: Campo
authors.forename: Christophe
authors.initials: C
authors.lastname: Combescure
mesh_terms: D000367:Age Factors; D002318:Cardiovascular Diseases / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology; D000077144:Clopidogrel; D006801:Humans; D010974:Platelet Aggregation; D010979:Platelet Function Tests; D011237:Predictive Value of Tests; D012306:Risk; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000077144:Clopidogrel; D013988:Ticlopidine
keywords: Clopidogrel; cardiovascular diseases; drug response; ischaemic events; platelets