Advertisement

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

      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.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • McLean E.
        • Cogswell M.
        • Egli I.
        • Wojdyla D.
        • de Benoist B.
        Worldwide prevalence of anaemia, WHO vitamin and mineral nutrition information system, 1993-2005.
        Public Health Nutr. 2009; 12: 444-454
        • Pilgrim T.
        • Vetterli F.
        • Kalesan B.
        • Stefanini G.G.
        • Raber L.
        • Stortecky S.
        • Gloekler S.
        • Binder R.K.
        • Wenaweser P.
        • Moschovitis A.
        • Khattab A.A.
        • Buellesfeld L.
        • Zwahlen M.
        • Meier B.
        • Juni P.
        • Windecker S.
        The impact of anemia on long-term clinical outcome in patients undergoing revascularization with the unrestricted use of drug-eluting stents.
        Circ Cardiovasc Interv. 2012; 5: 202-210
        • Tsujita K.
        • Nikolsky E.
        • Lansky A.J.
        • Dangas G.
        • Fahy M.
        • Brodie B.R.
        • Dudek D.
        • Mockel M.
        • Ochala A.
        • Mehran R.
        • Stone G.W.
        Impact of anemia on clinical outcomes of patients with ST-segment elevation myocardial infarction in relation to gender and adjunctive antithrombotic therapy (from the HORIZONS-AMI trial).
        Am J Cardiol. 2010; 105: 1385-1394
        • Kunadian V.
        • Mehran R.
        • Lincoff A.M.
        • Feit F.
        • Manoukian S.V.
        • Hamon M.
        • Cox D.A.
        • Dangas G.D.
        • Stone G.W.
        Effect of anemia on frequency of short- and long-term clinical events in acute coronary syndromes (from the Acute Catheterization and Urgent Intervention Triage Strategy trial).
        Am J Cardiol. 2014; 114: 1823-1829
        • Riley R.F.
        • Newby L.K.
        • Don C.W.
        • Alexander K.P.
        • Peterson E.D.
        • Peng S.A.
        • Gandhi S.K.
        • Kutcher M.A.
        • Amsterdam E.A.
        • Herrington D.M.
        Guidelines-based treatment of anaemic STEMI patients: practice patterns and effects on in-hospital mortality: a retrospective analysis from the NCDR.
        Eur Heart J Acute Cardiovasc Care. 2013; 2: 35-43
        • Santos-Gallego C.G.
        • Picatoste B.
        • Badimon J.J.
        Pathophysiology of acute coronary syndrome.
        Curr Atheroscler Rep. 2014; 16: 401
        • Ataga K.I.
        Hypercoagulability and thrombotic complications in hemolytic anemias.
        Haematologica. 2009; 94: 1481-1484
        • Franchini M.
        • Targher G.
        • Montagnana M.
        • Lippi G.
        Iron and thrombosis.
        Ann Hematol. 2008; 87: 167-173
        • Toma C.
        • Zahr F.
        • Moguilanski D.
        • Grate S.
        • Semaan R.W.
        • Lemieux N.
        • Lee J.S.
        • Cortese-Hassett A.
        • Mulukutla S.
        • Rao S.V.
        • Marroquin O.C.
        Impact of anemia on platelet response to clopidogrel in patients undergoing percutaneous coronary stenting.
        Am J Cardiol. 2012; 109: 1148-1153
        • Dale G.L.
        • Alberio L.
        Is there a correlation between raised erythropoietin and thrombotic events in sickle-cell anaemia?.
        Lancet. 1998; 352: 566-567
        • Aarts P.A.
        • Heethaar R.M.
        • Sixma J.J.
        Red blood cell deformability influences platelets–vessel wall interaction in flowing blood.
        Blood. 1984; 64: 1228-1233
        • Giustino G.
        • Baber U.
        • Sartori S.
        • Mehran R.
        • Mastoris I.
        • Kini A.S.
        • Sharma S.K.
        • Pocock S.J.
        • Dangas G.D.
        Duration of dual antiplatelet therapy after drug-eluting stent implantation: a systematic review and meta-analysis of randomized controlled trials.
        J Am Coll Cardiol. 2015; 65: 1298-1310
        • Genereux P.
        • Rutledge D.R.
        • Palmerini T.
        • Caixeta A.
        • Kedhi E.
        • Hermiller J.B.
        • Wang J.
        • Krucoff M.W.
        • Jones-McMeans J.
        • Sudhir K.
        • Simonton C.A.
        • Serruys P.W.
        • Stone G.W.
        Stent thrombosis and dual antiplatelet therapy interruption with everolimus-eluting stents: insights from the Xience V coronary stent system trials.
        Circ Cardiovasc Interv. 2015; 8: 8
        • Kirtane A.J.
        • Parikh P.B.
        • Stuckey T.D.
        • Xu K.
        • Witzenbichler B.
        • Weisz G.
        • Rinaldi M.J.
        • Neumann F.J.
        • Metzger D.C.
        • Henry T.D.
        • Cox D.A.
        • Duffy P.L.
        • Brodie B.R.
        • Mazzaferri Jr., E.L.
        • Parvataneni R.
        • Maehara A.
        • Genereux P.
        • Mehran R.
        • Stone G.W.
        Is there an ideal level of platelet P2Y12-receptor inhibition in patients undergoing percutaneous coronary intervention?: “Window” analysis from the ADAPT-DES study (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents).
        JACC Cardiovasc Interv. 2015; 8: 1978-1987
        • Mauri L.
        • Kereiakes D.J.
        • Yeh R.W.
        • Driscoll-Shempp P.
        • Cutlip D.E.
        • Steg P.G.
        • Normand S.L.
        • Braunwald E.
        • Wiviott S.D.
        • Cohen D.J.
        • Holmes Jr., D.R.
        • Krucoff M.W.
        • Hermiller J.
        • Dauerman H.L.
        • Simon D.I.
        • Kandzari D.E.
        • Garratt K.N.
        • Lee D.P.
        • Pow T.K.
        • Ver Lee P.
        • Rinaldi M.J.
        • Massaro J.M.
        • Investigators DS
        Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents.
        N Engl J Med. 2014; 371: 2155-2166
        • Stone G.W.
        • Witzenbichler B.
        • Weisz G.
        • Rinaldi M.J.
        • Neumann F.J.
        • Metzger D.C.
        • Henry T.D.
        • Cox D.A.
        • Duffy P.L.
        • Mazzaferri E.
        • Gurbel P.A.
        • Xu K.
        • Parise H.
        • Kirtane A.J.
        • Brodie B.R.
        • Mehran R.
        • Stuckey T.D.
        Platelet reactivity and clinical outcomes after coronary artery implantation of drug-eluting stents (ADAPT-DES): a prospective multicentre registry study.
        Lancet. 2013; 382: 614-623
        • Nutritional anaemias
        Report of a WHO scientific group.
        World Health Organ Tech Rep Ser. 1968; 405: 5-37
        • Pereira A.A.
        • Sarnak M.J.
        Anemia as a risk factor for cardiovascular disease.
        Kidney Int Suppl. 2003; : S32-S39
        • Sarnak M.J.
        • Tighiouart H.
        • Manjunath G.
        • MacLeod B.
        • Griffith J.
        • Salem D.
        • Levey A.S.
        Anemia as a risk factor for cardiovascular disease in the Atherosclerosis Risk in Communities (ARIC) study.
        J Am Coll Cardiol. 2002; 40: 27-33
        • Bellotto F.
        • Fagiuoli S.
        • Pavei A.
        • Gregory S.A.
        • Cati A.
        • Silverj E.
        • Plebani M.
        • Zaninotto M.
        • Mancuso T.
        • Iliceto S.
        Anemia and ischemia: myocardial injury in patients with gastrointestinal bleeding.
        Am J Med. 2005; 118: 548-551
        • Vlagopoulos P.T.
        • Tighiouart H.
        • Weiner D.E.
        • Griffith J.
        • Pettitt D.
        • Salem D.N.
        • Levey A.S.
        • Sarnak M.J.
        Anemia as a risk factor for cardiovascular disease and all-cause mortality in diabetes: the impact of chronic kidney disease.
        J Am Soc Nephrol. 2005; 16: 3403-3410
        • Weiss G.
        • Goodnough L.T.
        Anemia of chronic disease.
        N Engl J Med. 2005; 352: 1011-1023
        • Pendyala L.K.
        • Loh J.P.
        • Lhermusier T.
        • Minha S.
        • Magalhaes M.A.
        • Torguson R.
        • Chen F.
        • Satler L.F.
        • Pichard A.D.
        • Waksman R.
        Does baseline hematocrit influence the assays of on-treatment platelet reactivity to clopidogrel?.
        Am Heart J. 2014; 168: 545-551
        • Schneider D.J.
        Factors contributing to increased platelet reactivity in people with diabetes.
        Diabetes Care. 2009; 32: 525-527
        • Ibrahim H.
        • Schutt R.C.
        • Hannawi B.
        • DeLao T.
        • Barker C.M.
        • Kleiman N.S.
        Association of immature platelets with adverse cardiovascular outcomes.
        J Am Coll Cardiol. 2014; 64: 2122-2129
        • Price M.J.
        • Berger P.B.
        • Teirstein P.S.
        • Tanguay J.F.
        • Angiolillo D.J.
        • Spriggs D.
        • Puri S.
        • Robbins M.
        • Garratt K.N.
        • Bertrand O.F.
        • Stillabower M.E.
        • Aragon J.R.
        • Kandzari D.E.
        • Stinis C.T.
        • Lee M.S.
        • Manoukian S.V.
        • Cannon C.P.
        • Schork N.J.
        • Topol E.J.
        Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial.
        Jama. 2011; 305: 1097-1105
        • Collet J.P.
        • Cuisset T.
        • Range G.
        • Cayla G.
        • Elhadad S.
        • Pouillot C.
        • Henry P.
        • Motreff P.
        • Carrie D.
        • Boueri Z.
        • Belle L.
        • Van Belle E.
        • Rousseau H.
        • Aubry P.
        • Monsegu J.
        • Sabouret P.
        • O'Connor S.A.
        • Abtan J.
        • Kerneis M.
        • Saint-Etienne C.
        • Barthelemy O.
        • Beygui F.
        • Silvain J.
        • Vicaut E.
        • Montalescot G.
        Bedside monitoring to adjust antiplatelet therapy for coronary stenting.
        N Engl J Med. 2012; 367: 2100-2109
        • Genereux P.
        • Giustino G.
        • Witzenbichler B.
        • Weisz G.
        • Stuckey T.D.
        • Rinaldi M.J.
        • Neumann F.J.
        • Metzger D.C.
        • Henry T.D.
        • Cox D.A.
        • Duffy P.L.
        • Mazzaferri E.
        • Yadav M.
        • Francese D.P.
        • Palmerini T.
        • Kirtane A.J.
        • Litherland C.
        • Mehran R.
        • Stone G.W.
        Incidence, predictors, and impact of post-discharge bleeding after percutaneous coronary intervention.
        J Am Coll Cardiol. 2015; 66: 1036-1045
        • Nikolsky E.
        • Stone G.W.
        • Kirtane A.J.
        • Dangas G.D.
        • Lansky A.J.
        • McLaurin B.
        • Lincoff A.M.
        • Feit F.
        • Moses J.W.
        • Fahy M.
        • Manoukian S.V.
        • White H.D.
        • Ohman E.M.
        • Bertrand M.E.
        • Cox D.A.
        • Mehran R.
        Gastrointestinal bleeding in patients with acute coronary syndromes: incidence, predictors, and clinical implications: analysis from the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial.
        J Am Coll Cardiol. 2009; 54: 1293-1302
        • Chan F.K.
        • Ching J.Y.
        • Hung L.C.
        • Wong V.W.
        • Leung V.K.
        • Kung N.N.
        • Hui A.J.
        • Wu J.C.
        • Leung W.K.
        • Lee V.W.
        • Lee K.K.
        • Lee Y.T.
        • Lau J.Y.
        • To K.F.
        • Chan H.L.
        • Chung S.C.
        • Sung J.J.
        Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding.
        N Engl J Med. 2005; 352: 238-244
        • Guslandi M.
        Gastric toxicity of antiplatelet therapy with low-dose aspirin.
        Drugs. 1997; 53: 1-5
        • Palmerini T.
        • Benedetto U.
        • Bacchi-Reggiani L.
        • Della Riva D.
        • Biondi-Zoccai G.
        • Feres F.
        • Abizaid A.
        • Hong M.K.
        • Kim B.K.
        • Jang Y.
        • Kim H.S.
        • Park K.W.
        • Genereux P.
        • Bhatt D.L.
        • Orlandi C.
        • De Servi S.
        • Petrou M.
        • Rapezzi C.
        • Stone G.W.
        Mortality in patients treated with extended duration dual antiplatelet therapy after drug-eluting stent implantation: a pairwise and Bayesian network meta-analysis of randomised trials.
        Lancet. 2015; 385: 2371-2382