Ajay J Kirtane1, Puja B Parikh2, Thomas D Stuckey3, Ke Xu4, Bernhard Witzenbichler5, Giora Weisz6, Michael J Rinaldi7, Franz-Josef Neumann8, D Christopher Metzger9, Timothy D Henry10, David A Cox11, Peter L Duffy12, Bruce R Brodie3, Ernest L Mazzaferri13, Rupa Parvataneni4, Akiko Maehara14, Philippe Généreux15, Roxana Mehran16, Gregg W Stone14. 1. Division of Cardiology, Columbia University/NewYork-Presbyterian Hospital, New York, New York; Cardiovascular Research Foundation, New York, New York. Electronic address: akirtane@columbia.edu. 2. Division of Cardiology, Columbia University/NewYork-Presbyterian Hospital, New York, New York. 3. LeBauer Cardiovascular Research Foundation/Moses Cone Hospital, Greensboro, North Carolina. 4. Cardiovascular Research Foundation, New York, New York. 5. Amper Kliniken AG, Dachau, Germany. 6. Division of Cardiology, Columbia University/NewYork-Presbyterian Hospital, New York, New York; Cardiovascular Research Foundation, New York, New York; Department of Cardiology, Shaare Zedek Medical Center, Jerusalem, Israel. 7. Sanger Heart and Vascular Institute/Carolinas HealthCare System, Charlotte, North Carolina. 8. Department of Cardiology, Universitäts-Herzzentrum Freiburg Bad Krozingen, Bad Krozingen, Germany. 9. Wellmont CVA Heart Institute, Kingsport, Tennessee. 10. Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, Minnesota; Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California. 11. Department of Medicine, Lehigh Valley Health Network, Allentown, Pennsylvania. 12. Reid Heart Center, FirstHealth of the Carolinas, Pinehurst, North Carolina. 13. Department of Medicine, The Ohio State University, Columbus, Ohio. 14. Division of Cardiology, Columbia University/NewYork-Presbyterian Hospital, New York, New York; Cardiovascular Research Foundation, New York, New York. 15. Division of Cardiology, Columbia University/NewYork-Presbyterian Hospital, New York, New York; Cardiovascular Research Foundation, New York, New York; Hôpital du Sacré-Coeur de Montréal, Montréal, Québec, Canada. 16. Cardiovascular Research Foundation, New York, New York; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Abstract
OBJECTIVES: This study sought to determine whether there is an ideal level of platelet reactivity (PR) to optimize safety and efficacy within the large multicenter ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents) study of 8,582 patients receiving successful drug-eluting stent implantation. BACKGROUND: Patients with high PR on clopidogrel have a greater incidence of adverse ischemic events after stent implantation, whereas low PR may increase bleeding. Due to limited sample size, previous studies have not been able to adjust for differences in baseline characteristics that may confound the relationship of PR and outcomes. METHODS: In the ADAPT-DES study, routine platelet function testing (VerifyNow) was performed following clopidogrel loading. To characterize the independent association between PR and clinical events, patients were stratified into quintiles of P2Y12 reaction units (PRU). RESULTS: The PRU medians of the 5 quintiles were 57, 130, 187, 244, and 317 (most to least inhibited). There was a monotonic association between successively higher PRU quintiles and stent thrombosis, whereas for clinically relevant bleeding, the greatest risk occurred in the lowest PRU quintile, with similar risks across the 4 higher quintiles. These relationships remained significant in fully adjusted multivariable analyses (adjusted hazard ratio [HR] for stent thrombosis in Q5 versus Q1: 2.32; 95% confidence interval [CI]: 1.17 to 4.59; p = 0.02; adjusted HR for clinically relevant bleeding in Q5 versus Q1: 0.61; 95% CI: 0.47 to 0.77; p < 0.001). However, there were no significant independent associations between the level of PRU and mortality. CONCLUSIONS: In this large observational study, increasing PRU was associated with a monotonic increase in stent thrombosis, whereas bleeding risk was confined to the lowest PRU quintile, suggesting an optimal therapeutic window of platelet inhibition at moderately inhibited PRU. However, there was no demonstrable threshold effect for PRU and mortality in adjusted analyses, perhaps due to the offsetting impact of bleeding and ischemia across the spectrum of platelet inhibition. (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents [ADAPT-DES]; NCT00638794).
OBJECTIVES: This study sought to determine whether there is an ideal level of platelet reactivity (PR) to optimize safety and efficacy within the large multicenter ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents) study of 8,582 patients receiving successful drug-eluting stent implantation. BACKGROUND:Patients with high PR on clopidogrel have a greater incidence of adverse ischemic events after stent implantation, whereas low PR may increase bleeding. Due to limited sample size, previous studies have not been able to adjust for differences in baseline characteristics that may confound the relationship of PR and outcomes. METHODS: In the ADAPT-DES study, routine platelet function testing (VerifyNow) was performed following clopidogrel loading. To characterize the independent association between PR and clinical events, patients were stratified into quintiles of P2Y12 reaction units (PRU). RESULTS: The PRU medians of the 5 quintiles were 57, 130, 187, 244, and 317 (most to least inhibited). There was a monotonic association between successively higher PRU quintiles and stent thrombosis, whereas for clinically relevant bleeding, the greatest risk occurred in the lowest PRU quintile, with similar risks across the 4 higher quintiles. These relationships remained significant in fully adjusted multivariable analyses (adjusted hazard ratio [HR] for stent thrombosis in Q5 versus Q1: 2.32; 95% confidence interval [CI]: 1.17 to 4.59; p = 0.02; adjusted HR for clinically relevant bleeding in Q5 versus Q1: 0.61; 95% CI: 0.47 to 0.77; p < 0.001). However, there were no significant independent associations between the level of PRU and mortality. CONCLUSIONS: In this large observational study, increasing PRU was associated with a monotonic increase in stent thrombosis, whereas bleeding risk was confined to the lowest PRU quintile, suggesting an optimal therapeutic window of platelet inhibition at moderately inhibited PRU. However, there was no demonstrable threshold effect for PRU and mortality in adjusted analyses, perhaps due to the offsetting impact of bleeding and ischemia across the spectrum of platelet inhibition. (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents [ADAPT-DES]; NCT00638794).
Authors: Andrew Yang; Quin Pon; Andrea Lavoie; Jennifer J Crawford; Sebastian Harenberg; Rodney H Zimmermann; Jeff Booker; Sheila Kelly; Shahar Lavi; Warren J Cantor; Shamir R Mehta; Akshay Bagai; Shaun G Goodman; Asim N Cheema; Payam Dehghani Journal: J Thromb Thrombolysis Date: 2018-02 Impact factor: 2.300
Authors: Axel Rosengart; Malie K Collins; Philipp Hendrix; Ryley Uber; Melissa Sartori; Abhi Jain; Jennifer Mao; Oded Goren; Clemens M Schirmer; Christoph J Griessenauer Journal: Interv Neuroradiol Date: 2021-02-04 Impact factor: 1.764