TY - JOUR
T1 - Vascular risk levels affect the predictive value of platelet reactivity for the occurrence of MACE in patients on clopidogrel
T2 - Systematic review and meta-analysis of individual patient data
AU - Reny, Jean Luc
AU - Fontana, Pierre
AU - Hochholzer, Willibald
AU - Neumann, Franz Josef
AU - ten Berg, Jurriën
AU - Janssen, Paul W.
AU - Geisler, Tobias
AU - Gawaz, Meinrad
AU - Marcucci, Rossella
AU - Gori, Anna Maria
AU - Cuisset, Thomas
AU - Alessi, Marie Christine
AU - Berdagué, Philippe
AU - Gurbel, Paul A.
AU - Yong, Gerald
AU - Angiolillo, Dominick J.
AU - Aradi, Daniel
AU - Beigel, Roy
AU - Campo, Gianluca
AU - Combescure, Christophe
N1 - Publisher Copyright:
© Schattauer 2016.
PY - 2016/4
Y1 - 2016/4
N2 - 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 re-classification 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.
AB - 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 re-classification 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.
KW - Cardiovascular diseases
KW - Clopidogrel
KW - Drug response
KW - Ischaemic events
KW - Platelets
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U2 - 10.1160/TH15-09-0742
DO - 10.1160/TH15-09-0742
M3 - Review article
C2 - 26607655
AN - SCOPUS:84964786023
SN - 0340-6245
VL - 115
SP - 844
EP - 855
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
IS - 4
ER -