Impact of Anemia on Platelet Reactivity and Ischemic and Bleeding Risk: From the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents Study

Gennaro Giustino, Ajay J. Kirtane, Usman Baber, Philippe Généreux, Bernhard Witzenbichler, Franz Josef Neumann, Giora Weisz, Akiko Maehara, Michael J. Rinaldi, Christopher Metzger, Timothy D. Henry, David A. Cox, Peter L. Duffy, Ernest L. Mazzaferri, Bruce R. Brodie, Thomas D. Stuckey, Paul A. Gurbel, George D. Dangas, Dominic P. Francese, Ozgu OzanRoxana Mehran, Gregg W. Stone

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Anemic patients remain at increased risk of ischemic and bleeding events. Whether the effects of hemoglobin levels on thrombotic and bleeding risk are independent of platelet reactivity on clopidogrel, however, remains unknown. Patients from the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents study were categorized by the presence of anemia at baseline, defined according the World Health Organization criteria. Platelet reactivity was measured with VerifyNow assay; high platelet reactivity (HPR) on clopidogrel was defined as platelet reactive units value >208. Of 8,413 patients included in the study cohort, 1,816 (21.6%) had anemia. HPR was more prevalent in patients with anemia (58.3% vs 38.4%; p <0.001), an association that persisted after multivariate adjustment (adjusted odds ratio: 2.04; 95% confidence interval [CI]: 1.82 to 2.29; p <0.0001). Patients with anemia had higher 2-year rates of major adverse cardiac events (9.5% vs 5.6%; p <0.0001), major bleeding (11.8% vs 7.7%; p <0.0001), and all-cause mortality (4.0% vs 1.4%; p <0.0001); however, after adjustment for baseline clinical confounders, including HPR, anemia was no longer significantly associated with major adverse cardiac events but was still independently associated with all-cause mortality (adjusted HR 1.61, 95% CI 1.23 to 2.12; p <0.0001) and major bleeding (adjusted HR 1.42, 95% CI 1.20 to 1.68; p <0.0001). The effect of HPR on clinical outcomes was uniform according to anemia status, without evidence of interaction. In conclusion, anemia independently correlated with HPR. After percutaneous coronary intervention with drug-eluting stents, anemia at baseline was significantly associated with higher 2-year hemorrhagic and mortality risk; conversely, its association with ischemic risk was attenuated after multivariate adjustment, including HPR.

Original languageEnglish (US)
Pages (from-to)1877-1883
Number of pages7
JournalAmerican Journal of Cardiology
Issue number12
StatePublished - Jun 15 2016

Bibliographical note

Funding Information:
Dr. Kirtane: institutional research grants to Columbia University from Boston Scientific, Medtronic, Abbott Vascular, Abiomed, St. Jude Medical, Vascular Dynamics, and Eli Lilly. Dr. Genereux receives Speaker's fee from Abbott Vascular and Edwards Lifescience; consulting fee from Cardiovascular Systems Inc.; and institutional research grant from Boston Scientific. Dr. Weisz is a member of Advisory board—AngioSlide, AstraZeneca, Calore Medical, Corindus, Medivizor, Medtronic. Dr. Rinaldi is a consultant for Abbott, Boston Scientific, St. Jude Medical, Volcano. Dr. Stuckey is a member of Advisory board—Boston Scientific; speaker honoraria—Boston Scientific, Eli Lilly/Daiichi-Sankyo. Dr. Maehara receives grant support from Boston Scientific; a consultant of Boston Scientific, ACIST; speaker fee from St. Jude Medical. Dr. Witzenbichler is a consultant for Volcano. Dr. Metzger receives symposium honoraria from Abbott Vascular, Boston Scientific, Bard; hand on proctor fees from Abbott Vascular, TriVascular. Dr. Henry is a member of scientific advisory board—Abbott Vascular, Boston Scientific, The Medicines Company; steering committee: TRANSLATE sponsored by Eli Lilly and Daiichi-Sankyo. Dr. Cox is a consultant for Abbott Vascular, Boston Scientific Corporation, Medtronic, The Medicines Company. Dr. Duffy is a consultant/speaker for Philips Medical/Volcano. Dr. Mehran receives institutional research grant support from The Medicines Company, Bristol-Myers Squibb/Sanofi and Eli Lilly and Company/Daiichi-Sankyo; consulting from Abbott Vascular, AstraZeneca, Boston Scientific, Covidien, Janssen Pharmaceuticals, Regado Biosciences, Maya Medical, Merck & Co., and The Medicines Company. Dr Gurbel is a consultant for Daiichi Sankyo, Bayer, AstraZeneca, Merck, Medtronic, CSL, and Haemonetics; receives grants from National Institutes of Health, Daiichi Sankyo, CSL, AstraZeneca, Harvard Clinical Research Institute, Haemonetics, Coramed, and Duke Clinical Research Institute; payment for lectures including service on speakers' bureaus of AstraZeneca, Daiichi Sankyo, Merck; stock or stock options—Merck, Medtronic, and Pfizer; patents in the area of personalized antiplatelet therapy and interventional cardiology. The other authors have no conflicts of interest to disclose.

Funding Information:
The ADAPT-DES study (NCT00638794) was sponsored by the Cardiovascular Research Foundation , with funding provided by Boston Scientific, Abbott Vascular, Medtronic, Cordis, Biosensors, The Medicines Company, Daiichi-Sankyo, Eli Lilly, Volcano, and Accumetrics.

Publisher Copyright:
© 2016 Elsevier Inc.


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