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 Genereux, 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 Ozan & 2 others Roxana Mehran, Gregg W. Stone

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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
Volume117
Issue number12
DOIs
StatePublished - Jun 15 2016
Externally publishedYes

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Drug-Eluting Stents
Anemia
Blood Platelets
Hemorrhage
clopidogrel
Therapeutics
Confidence Intervals
Mortality
Percutaneous Coronary Intervention
Hemoglobins
Cohort Studies
Odds Ratio

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Giustino, Gennaro ; Kirtane, Ajay J. ; Baber, Usman ; Genereux, Philippe ; Witzenbichler, Bernhard ; Neumann, Franz Josef ; Weisz, Giora ; Maehara, Akiko ; Rinaldi, Michael J. ; Metzger, Christopher ; Henry, Timothy D. ; Cox, David A. ; Duffy, Peter L. ; Mazzaferri, Ernest L. ; Brodie, Bruce R. ; Stuckey, Thomas D. ; Gurbel, Paul A. ; Dangas, George D. ; Francese, Dominic P. ; Ozan, Ozgu ; Mehran, Roxana ; Stone, Gregg W. / Impact of Anemia on Platelet Reactivity and Ischemic and Bleeding Risk : From the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents Study. In: American Journal of Cardiology. 2016 ; Vol. 117, No. 12. pp. 1877-1883.
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abstract = "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.",
author = "Gennaro Giustino and Kirtane, {Ajay J.} and Usman Baber and Philippe Genereux and Bernhard Witzenbichler and Neumann, {Franz Josef} and Giora Weisz and Akiko Maehara and Rinaldi, {Michael J.} and Christopher Metzger and Henry, {Timothy D.} and Cox, {David A.} and Duffy, {Peter L.} and Mazzaferri, {Ernest L.} and Brodie, {Bruce R.} and Stuckey, {Thomas D.} and Gurbel, {Paul A.} and Dangas, {George D.} and Francese, {Dominic P.} and Ozgu Ozan and Roxana Mehran and Stone, {Gregg W.}",
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Giustino, G, Kirtane, AJ, Baber, U, Genereux, P, Witzenbichler, B, Neumann, FJ, Weisz, G, Maehara, A, Rinaldi, MJ, Metzger, C, Henry, TD, Cox, DA, Duffy, PL, Mazzaferri, EL, Brodie, BR, Stuckey, TD, Gurbel, PA, Dangas, GD, Francese, DP, Ozan, O, Mehran, R & Stone, GW 2016, 'Impact of Anemia on Platelet Reactivity and Ischemic and Bleeding Risk: From the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents Study', American Journal of Cardiology, vol. 117, no. 12, pp. 1877-1883. https://doi.org/10.1016/j.amjcard.2016.03.034

Impact of Anemia on Platelet Reactivity and Ischemic and Bleeding Risk : From the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents Study. / Giustino, Gennaro; Kirtane, Ajay J.; Baber, Usman; Genereux, Philippe; Witzenbichler, Bernhard; Neumann, Franz Josef; Weisz, Giora; Maehara, Akiko; Rinaldi, Michael J.; Metzger, Christopher; Henry, Timothy D.; Cox, David A.; Duffy, Peter L.; Mazzaferri, Ernest L.; Brodie, Bruce R.; Stuckey, Thomas D.; Gurbel, Paul A.; Dangas, George D.; Francese, Dominic P.; Ozan, Ozgu; Mehran, Roxana; Stone, Gregg W.

In: American Journal of Cardiology, Vol. 117, No. 12, 15.06.2016, p. 1877-1883.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Impact of Anemia on Platelet Reactivity and Ischemic and Bleeding Risk

T2 - From the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents Study

AU - Giustino, Gennaro

AU - Kirtane, Ajay J.

AU - Baber, Usman

AU - Genereux, Philippe

AU - Witzenbichler, Bernhard

AU - Neumann, Franz Josef

AU - Weisz, Giora

AU - Maehara, Akiko

AU - Rinaldi, Michael J.

AU - Metzger, Christopher

AU - Henry, Timothy D.

AU - Cox, David A.

AU - Duffy, Peter L.

AU - Mazzaferri, Ernest L.

AU - Brodie, Bruce R.

AU - Stuckey, Thomas D.

AU - Gurbel, Paul A.

AU - Dangas, George D.

AU - Francese, Dominic P.

AU - Ozan, Ozgu

AU - Mehran, Roxana

AU - Stone, Gregg W.

PY - 2016/6/15

Y1 - 2016/6/15

N2 - 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.

AB - 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.

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