The prognostic impact of high on-treatment platelet reactivity with aspirin or ADP receptor antagonists: systematic review and meta-analysis.
OBJECTIVE
Negative results of recent randomized clinical trials testing the hypothesis of target therapy for patients with high on-treatment platelet reactivity (HOPR) have questioned its independent impact on clinical outcomes. 26 studies with 28.178 patients were included, with a median age of 66.8 (64-68) and 22.7% (22.4-27.8), of female gender. After a median follow-up of 1 year (0.1-1), cardiac adverse events occurred in 8.3% (3-11; all results are reported as median and interquartile range) of patients. Pooling all studies together, on-treatment platelet reactivity significantly increased the risk of adverse events (OR 1.33 [1.09, 1.64], I(2) = 0%). However, a sensitivity analysis showed that HOPR did not increase the risk of adverse events for patients with ACS, AMI, or stable angina as well as patients resistant to aspirin, ADP antagonists, or both. For all studies, publication bias was formally evident; after adjusting for this, HOPR did not significantly increase adverse cardiac events (OR 1.1 : 0.89-1.22, I(2) 0%).


CONCLUSIONS
After adjusting for clinical confounders (like risk factors and clinical presentation) and for relevant publication bias, HOPR was not an independent prognostic indicator in unselected patients with both stable and unstable coronary disease for an adverse cardiac event. The clinical importance of HOPR for high-risk populations remains to be assessed.
Department of Internal Medicine, Division of Cardiology, Città Della Salute e Della Scienza, Turin, Italy.
Fabrizio
F
D'Ascenzo
Department of Internal Medicine, Division of Cardiology, Città Della Salute e Della Scienza, Turin, Italy.
Umberto
U
Barbero
Department of Internal Medicine, Division of Cardiology, Città Della Salute e Della Scienza, Turin, Italy.
Marta
M
Bisi
Department of Internal Medicine, Division of Cardiology, Città Della Salute e Della Scienza, Turin, Italy.
Claudio
C
Moretti
Department of Internal Medicine, Division of Cardiology, Città Della Salute e Della Scienza, Turin, Italy.
Pierluigi
P
Omedè
Department of Internal Medicine, Division of Cardiology, Città Della Salute e Della Scienza, Turin, Italy.
Enrico
E
Cerrato
Department of Internal Medicine, Division of Cardiology, Città Della Salute e Della Scienza, Turin, Italy.
Giorgio
G
Quadri
Department of Internal Medicine, Division of Cardiology, Città Della Salute e Della Scienza, Turin, Italy.
Federico
0000-0002-5402-6826
F
Conrotto
Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.
Giuseppe Biondi
GB
Zoccai
Mid America Heart Institute at Saint Luke's Hospital, Kansas City, MO, USA.
James J
JJ
DiNicolantonio
Politecnico of Turin, Turin, Italy.
Mauro
M
Gasparini
New York University School of Medicine, New York, NY, USA.
Sripal
S
Bangalore
Department of Internal Medicine, Division of Cardiology, Città Della Salute e Della Scienza, Turin, Italy.
Fiorenzo
F
Gaita
D000368:Aged; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011379:Prognosis; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology*; D016896:Treatment Outcome
D058921:Purinergic P2Y Receptor Antagonists; D001241:Aspirin