Concomitant proton-pump inhibitor use, platelet activity, and clinical outcomes in patients with acute coronary syndromes treated with prasugrel versus clopidogrel and managed without revascularization: Insights from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes trial - 18/09/15
, Deepak L. Bhatt, MD, MPH b, Matthew T. Roe, MD, MHS c, d, Yuliya Lokhnygina, PhD d, Benjamin Neely, MS d, Ramón Corbalán, MD e, José L. Leiva-Pons, MD f, Felipe Martinez, MD g, Shaun G. Goodman, MD, MSc h, Kenneth J. Winters, MD i, Freek W.A. Verheugt, MD j, Paul W. Armstrong, MD k, Harvey D. White, MB, ChB, DSc l, Keith A.A. Fox, MB, ChB m, Dorairaj Prabhakaran, MD, DM, MSc n, E. Magnus Ohman, MD c, dfor the
TRILOGY ACS investigators
Background |
Concomitant use of proton-pump inhibitors (PPIs) has been implicated in diminished antiplatelet response to clopidogrel and an increased risk of ischemic events, but primarily among patients undergoing percutaneous coronary intervention. We sought to examine the potential influence of interactions between PPIs and clopidogrel versus prasugrel on platelet reactivity and clinical outcomes after acute coronary syndromes (ACS) in patients managed medically without revascularization.
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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| Mauricio G Cohen, MD served as guest editor for this article. |
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| Funding: The TRILOGY ACS study was funded by Daiichi Sankyo and Eli Lilly and Co. |
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| Conflict of interest: Jose Carlos Nicolau is a consultant for AstraZeneca, Sanofi, and Bayer; has received grants from Sanofi, GlaxoSmithKline, Bayer, and Novartis; and has received lecture fees from Sanofi, Daiichi Sankyo, AstraZeneca, Bayer, and BMS. Deepak L Bhatt discloses the following relationships: advisory board: Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; board of directors: Boston VA Research Institute and Society of Cardiovascular Patient Care; chair: American Heart Association Get With The Guidelines Steering Committee; data monitoring committees: Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, Population Health Research Institute; honoraria: American College of Cardiology (editor, Clinical Trials, Cardiosource), Belvoir Publications (editor in chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (editor in chief, Journal of Invasive Cardiology), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), WebMD (CME steering committees); others: Clinical Cardiology (deputy editor), Journal of the American College of Cardiology (section editor, pharmacology); research grants: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Roche, Sanofi Aventis, and The Medicines Company; and unfunded research: FlowCo, PLx Pharma, and Takeda. Matthew T Roe reports research grants from Eli Lilly, Daiichi Sankyo, Ferring Pharmaceuticals, Janssen Pharmaceuticals, KAI Pharmaceuticals, the Familial Hypercholesterolemia Foundation, and Sanofi-Aventis. He also receives consulting payments or honoraria from AstraZeneca, Eli Lilly, Merck, Janssen, Elsevier Publishers, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Pri-Med, and Regeneron. All conflicts of interest are listed at https://www.dcri.org/about-us/conflict-of-interest. Yuliya Lokhnygina, Benjamin Neely, Ramón Corbalan, and José Leiva-Pons have no disclosures. Felipe Martinez has consulted for and received travel fees from Eli Lilly and Daiichi Sankyo. Shaun G Goodman has consulted for Sanofi-Aventis, Eli Lilly, AstraZeneca, Bayer, and Bristol-Myers Squibb; and has received grants from Johnson & Johnson, AstraZeneca, Bristol-Myers Squibb, Sanofi-Aventis, Eli Lilly, Boehringer Ingelheim, Actelion, Bayer, Merck, Daiichi Sankyo, Servier, and Pfizer. Kenneth J Winters receives a salary and other financial benefits from Eli Lilly. Freek W A Verheugt has consulted for AstraZeneca and Boehringer Ingelheim. Paul W Armstrong has consulted for Merck, Eli Lilly, and GlaxoSmithKline; has received grants from Boehringer Ingelheim, Hoffmann-La Roche & Sanofi-Aventis Canada Inc in conjunction with Leuven Coordinating Centre, Amylin in conjunction with Duke Clinical Research Institute, Regado Biosciences, Merck, GlaxoSmithKline, and AstraZeneca in conjunction with Uppsala Clinical Research Centre; and has received other financial benefits from AstraZeneca and Eli Lilly. Harvey D White has received grants from Sanofi-Aventis, Eli Lilly, The Medicines Company, the National Institutes of Health, Pfizer, Roche, Johnson & Johnson, Schering-Plough, Merck Sharp & Dohme, AstraZeneca, GlaxoSmithKline, Daiichi Sankyo, and Bristol-Myers Squibb; and has served as a board member for Merck Sharp & Dohme and Regado Biosciences. Keith AA Fox has consulted for Boehringer Ingelheim, Sanofi-Aventis, AstraZeneca, and Johnson & Johnson/Bayer; and has received grants from Eli Lilly. Dorairaj Prabhakaran has received travel support and honoraria from Eli Lilly and has received grants from the Lilly Foundation and Medtronic Foundation. E Magnus Ohman has consulted for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Liposcience, Merck, Pozen, Hoffmann-La Roche, Sanofi-Aventis, The Medicines Company, and Web MD; has received grants from Daiichi Sankyo, Eli Lilly, and Gilead Sciences; has received lecture fees from Gilead Sciences, Boehringer Ingelheim, and The Medicines Company; and has received travel expenses from Daiichi Sankyo and Eli Lilly. |
Vol 170 - N° 4
P. 683 - ottobre 2015 Ritorno al numero
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