Abstract | UNLABELLED: METHODS: This analysis from the TRILOGY ACS trial focused upon the 7,243 ACS patients aged <75 years who were managed without revascularization, randomized to clopidogrel or prasugrel, and followed for a median of 17 months. Proton-pump inhibitor type and use were assessed at each study visit, and 2,049 of the patients in this cohort underwent serial platelet reactivity assessments. RESULTS:
Proton-pump inhibitor use (23%) was similar between the clopidogrel and prasugrel groups at baseline and throughout the study. Median on-treatment platelet reactivity values were consistently lower with prasugrel versus clopidogrel irrespective of PPI use. For the primary end point (composite of cardiovascular death, myocardial infarction [MI], or stroke), PPI use modified the unadjusted treatment effect of prasugrel versus clopidogrel (interaction P = .02). After adjusting for differences in baseline characteristics, this treatment effect modification was attenuated for the composite end point (interaction P = .06) but was significant for the MI component end point (interaction P = .01). Similarly, among patients on a PPI, the frequency of MI was significantly lower with prasugrel versus clopidogrel (hazard ratio = 0.61; 95% CI 0.42-0.88). These findings were similar by PPI type ( omeprazole and pantoprazole). CONCLUSIONS: Among ACS patients managed without revascularization, use of PPIs did not result in a differential antiplatelet response between prasugrel versus clopidogrel but was associated with a lower incidence of MI with prasugrel. These hypothesis-generating findings suggest that factors besides platelet reactivity may underlie the differential risk of MI observed by treatment assignment with PPI use.
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Authors | Jose Carlos Nicolau, Deepak L Bhatt, Matthew T Roe, Yuliya Lokhnygina, Benjamin Neely, Ramón Corbalán, José L Leiva-Pons, Felipe Martinez, Shaun G Goodman, Kenneth J Winters, Freek W A Verheugt, Paul W Armstrong, Harvey D White, Keith A A Fox, Dorairaj Prabhakaran, E Magnus Ohman, TRILOGY ACS investigators |
Journal | American heart journal
(Am Heart J)
Vol. 170
Issue 4
Pg. 683-694.e3
(Oct 2015)
ISSN: 1097-6744 [Electronic] United States |
PMID | 26386792
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier Inc. All rights reserved. |
Chemical References |
- Platelet Aggregation Inhibitors
- Proton Pump Inhibitors
- Purinergic P2Y Receptor Antagonists
- Clopidogrel
- Prasugrel Hydrochloride
- Ticlopidine
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Topics |
- Acute Coronary Syndrome
(blood, drug therapy)
- Aged
- Clopidogrel
- Dose-Response Relationship, Drug
- Double-Blind Method
- Drug Therapy, Combination
- Female
- Follow-Up Studies
- Humans
- Male
- Middle Aged
- Percutaneous Coronary Intervention
- Platelet Activation
(drug effects)
- Platelet Aggregation Inhibitors
(administration & dosage)
- Practice Guidelines as Topic
- Prasugrel Hydrochloride
(administration & dosage)
- Proton Pump Inhibitors
(administration & dosage)
- Purinergic P2Y Receptor Antagonists
(administration & dosage)
- Ticlopidine
(administration & dosage, analogs & derivatives)
- Time Factors
- Treatment Outcome
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