Canadian Journal of Cardiology
Clinical Research| Volume 34, ISSUE 3, P319-329, March 2018

Download started.


Associations Between Complex PCI and Prasugrel or Clopidogrel Use in Patients With Acute Coronary Syndrome Who Undergo PCI: From the PROMETHEUS Study

Published:December 27, 2017DOI:



      Potent P2Y12 inhibitors might offer enhanced benefit against thrombotic events in complex percutaneous coronary intervention (PCI). We examined prasugrel use and outcomes according to PCI complexity, as well as analyzing treatment effects according to thienopyridine type.


      PROMETHEUS was a multicentre observational study that compared clopidogrel vs prasugrel in acute coronary syndrome patients who underwent PCI (n = 19,914). Complex PCI was defined as PCI of the left main, bifurcation lesion, moderate-severely calcified lesion, or total stent length ≥ 30 mm. Major adverse cardiac events (MACE) were a composite of death, myocardial infarction, stroke, or unplanned revascularization. Outcomes were adjusted using multivariable Cox regression for effect of PCI complexity and propensity-stratified analysis for effect of thienopyridine type.


      The study cohort included 48.9% (n = 9735) complex and 51.1% (n = 10,179) noncomplex patients. Second generation drug-eluting stents were used in 70.1% complex and 66.2% noncomplex PCI patients (P < 0.0001). Complex PCI was associated with greater adjusted risk of 1-year MACE (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.20-1.39; P < 0.001). Prasugrel was prescribed in 20.7% of complex and 20.1% of noncomplex PCI patients (P = 0.30). Compared with clopidogrel, prasugrel significantly decreased adjusted risk for 1-year MACE in complex PCI (HR, 0.79; 95% CI, 0.68-0.92) but not noncomplex PCI (HR, 0.91; 95% CI, 0.77-1.08), albeit there was no evidence of interaction (P interaction = 0.281).


      Despite the use of contemporary techniques, acute coronary syndrome patients who undergo complex PCI had significantly higher rates of 1-year MACE. Adjusted magnitude of treatment effects with prasugrel vs clopidogrel were consistent in complex and noncomplex PCI without evidence of interaction.



      Les puissants inhibiteurs de P2Y12 peuvent procurer des bienfaits accrus contre les accidents thrombotiques dans le cadre d’une intervention coronarienne percutanée (ICP) complexe. Nous avons étudié l’utilisation du prasugrel et les résultats en fonction de la complexité de l'ICP, de même que nous avons analysé les effets du traitement selon le type de thiénopyridine.


      PROMETHEUS était une étude observationnelle multicentrique visant à comparer le clopidogrel au prasugrel chez des patients atteints d’un syndrome coronarien aigu qui ont subi une ICP (n = 19 914). L'ICP complexe était définie comme une ICP à l’artère coronaire gauche, une lésion de bifurcation, une lésion calcifiée modérée ou grave ou l’installation d’une endoprothèse d’une longueur totale d’au moins 30 mm. Les événements cardiaques indésirables majeurs (ECIM) comprenaient les décès, les infarctus du myocarde, les accidents vasculaires cérébraux ou les revascularisations non prévues. Les résultats ont été corrigés au moyen du modèle de régression de Cox à plusieurs variables pour tenir compte de l’effet de la complexité de l'ICP ainsi que d’une analyse stratifiée selon la propension pour tenir compte de l’effet du type de thiénopyridine.


      La cohorte de l’étude comprenait 48,9 % (n = 9735) de cas complexes et 51,1 % (n = 10 179) de cas non complexes. Des endoprothèses médicamentées de deuxième génération ont été utilisées chez 70,1 % des patients subissant une ICP complexe et chez 66,2 % des patients subissant une ICP non complexe (p < 0,0001). L'ICP complexe a été associée à un risque corrigé accru d'ECIM après un an (rapport de risques instantanés [RRI], 1,29; intervalle de confiance [IC] à 95 %, 1,20 à 1,39; p < 0,001). Le prasugrel a été prescrit à 20,7 % des patients ayant subi une ICP complexe et à 20,1 % des patients ayant subi une ICP non complexe (p = 0,30). Comparativement au clopidogrel, le prasugrel a considérablement réduit le risque corrigé d'ECIM après un an dans les cas d'ICP complexes (RRI, 0,79; IC à 95 %, 0,68 à 0,92), mais pas dans les cas d'ICP non complexes (RR, 0,91; IC à 95 %, 0,77 à 1,08), bien qu’il n’y ait eu aucun signe d’interaction (p interaction = 0,281).


      Malgré l’utilisation de techniques contemporaines, les patients atteints d’un syndrome coronarien aigu qui subissent une ICP ont affiché un taux considérablement accru d'ECIM après un an. L’ampleur corrigée des effets thérapeutiques du prasugrel par rapport au clopidogrel a été comparable dans les ICP et non complexes, sans signe d’interaction.
      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 to Canadian Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Cutlip D.E.
        • Chhabra A.G.
        • Baim D.S.
        • et al.
        Beyond restenosis: five-year clinical outcomes from second-generation coronary stent trials.
        Circulation. 2004; 110: 1226-1230
        • Stefanini G.G.
        • Serruys P.W.
        • Silber S.
        • et al.
        The impact of patient and lesion complexity on clinical and angiographic outcomes after revascularization with zotarolimus- and everolimus-eluting stents: a substudy of the RESOLUTE All Comers Trial (a randomized comparison of a zotarolimus-eluting stent with an everolimus-eluting stent for percutaneous coronary intervention).
        J Am Coll Cardiol. 2011; 57: 2221-2232
        • Giustino G.
        • Baber U.
        • Aquino M.
        • et al.
        Safety and efficacy of new-generation drug-eluting stents in women undergoing complex percutaneous coronary artery revascularization: from the WIN-DES collaborative patient-level pooled analysis.
        JACC Cardiovasc Interv. 2016; 9: 674-684
        • Giustino G.
        • Chieffo A.
        • Palmerini T.
        • et al.
        Efficacy and safety of dual antiplatelet therapy after complex PCI.
        J Am Coll Cardiol. 2016; 68: 1851-1864
        • Park S.J.
        • Park D.W.
        Percutaneous coronary intervention with stent implantation versus coronary artery bypass surgery for treatment of left main coronary artery disease: is it time to change guidelines?.
        Circ Cardiovasc Interv. 2009; 2: 59-68
        • Iakovou I.
        • Schmidt T.
        • Bonizzoni E.
        • et al.
        Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents.
        JAMA. 2005; 293: 2126-2130
        • Suh J.
        • Park D.W.
        • Lee J.Y.
        • et al.
        The relationship and threshold of stent length with regard to risk of stent thrombosis after drug-eluting stent implantation.
        JACC Cardiovasc Interv. 2010; 3: 383-389
        • Genereux P.
        • Madhavan M.V.
        • Mintz G.S.
        • et al.
        Ischemic outcomes after coronary intervention of calcified vessels in acute coronary syndromes. Pooled analysis from the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) and ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) TRIALS.
        J Am Coll Cardiol. 2014; 63: 1845-1854
        • Généreux P.K.
        • Palmerini T.
        • Witzenbichler B.
        • et al.
        Impact on two-year outcomes of percutaneous coronary intervention complexity and platelet reactivity among patients with stable coronary artery disease: insight from the ADAPT-DES study.
        J Am Coll Cardiol. 2015; 65 (abstract): A1725
        • Endo A.
        • Kawamura A.
        • Miyata H.
        • et al.
        Angiographic lesion complexity score and in-hospital outcomes after percutaneous coronary intervention.
        PLoS One. 2015; 10: e0127217
        • Mahmud E.
        • Naghi J.
        • Ang L.
        • et al.
        Demonstration of the safety and feasibility of robotically assisted percutaneous coronary intervention in complex coronary lesions: results of the CORA-PCI study (Complex Robotically Assisted Percutaneous Coronary Intervention).
        JACC Cardiovasc Interv. 2017; 10: 1320-1327
        • Mehran R.
        • Pocock S.J.
        • Stone G.W.
        • et al.
        Associations of major bleeding and myocardial infarction with the incidence and timing of mortality in patients presenting with non-ST-elevation acute coronary syndromes: a risk model from the ACUITY trial.
        Eur Heart J. 2009; 30: 1457-1466
        • Wiviott S.D.
        • Braunwald E.
        • McCabe C.H.
        • et al.
        Prasugrel versus clopidogrel in patients with acute coronary syndromes.
        N Engl J Med. 2007; 357: 2001-2015
        • Wallentin L.
        • Becker R.C.
        • Budaj A.
        • et al.
        Ticagrelor versus clopidogrel in patients with acute coronary syndromes.
        N Engl J Med. 2009; 361: 1045-1057
        • Levine G.N.
        • Bates E.R.
        • Bittl J.A.
        • et al.
        2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
        J Am Coll Cardiol. 2016; 68: 1082-1115
        • Tanguay J.F.
        • Bell A.D.
        • Ackman M.L.
        • et al.
        Focused 2012 update of the Canadian Cardiovascular Society guidelines for the use of antiplatelet therapy.
        Can J Cardiol. 2013; 29: 1334-1345
        • Rao S.V.
        • O'Grady K.
        • Pieper K.S.
        • et al.
        Impact of bleeding severity on clinical outcomes among patients with acute coronary syndromes.
        Am J Cardiol. 2005; 96: 1200-1206
        • Baber U.
        • Sartori S.
        • Aquino M.
        • et al.
        Use of prasugrel versus clopidogrel and outcomes in patients with acute coronary syndrome undergoing percutaneous coronary intervention in contemporary clinical practice: results from the PROMETHEUS study.
        Am Heart J. 2017; 188: 73-81
        • Fajadet J.
        • Chieffo A.
        Current management of left main coronary artery disease.
        Eur Heart J. 2012; 33: 36-50b
        • Iakovou I.
        • Kadota K.
        • Papamentzelopoulos S.
        • Pavlides G.
        • Mitsudo K.
        Is there a higher risk of stent thrombosis in bifurcation lesion or is it related to the technique?.
        EuroIntervention. 2010; 6: J107-J111
        • Armstrong E.J.
        • Yeo K.K.
        • Javed U.
        • et al.
        Angiographic stent thrombosis at coronary bifurcations: short- and long-term prognosis.
        JACC Cardiovasc Interv. 2012; 5: 57-63
        • Song P.S.
        • Song Y.B.
        • Lee J.M.
        • et al.
        Major predictors of long-term clinical outcomes after percutaneous coronary intervention for coronary bifurcation lesions with 2-stent strategy: patient-level analysis of the Korean bifurcation pooled cohorts.
        JACC Cardiovasc Interv. 2016; 9: 1879-1886
        • Dash D.
        Recent perspective on coronary artery bifurcation interventions.
        Heart Asia. 2014; 6: 18-25
        • Madhavan M.V.
        • Tarigopula M.
        • Mintz G.S.
        • et al.
        Coronary artery calcification: pathogenesis and prognostic implications.
        J Am Coll Cardiol. 2014; 63: 1703-1714
        • Applegate R.J.
        • Sacrinty M.T.
        • Kutcher M.A.
        • et al.
        Effect of length and diameter of drug-eluting stents versus bare-metal stents on late outcomes.
        Circ Cardiovasc Interv. 2009; 2: 35-42
        • Dangas G.D.
        • Claessen B.E.
        • Mehran R.
        • et al.
        Development and validation of a stent thrombosis risk score in patients with acute coronary syndromes.
        JACC Cardiovasc Interv. 2012; 5: 1097-1105
      1. EFFIENT (prasugrel) tablets [prescribing information]. Indianapolis, IN, Eli Lilly and Company.

        • Baber U.
        • Mehran R.
        • Giustino G.
        • et al.
        Coronary thrombosis and major bleeding after PCI with drug-eluting stents: risk scores from PARIS.
        J Am Coll Cardiol. 2016; 67: 2224-2234
        • Mehran R.
        • Pocock S.J.
        • Nikolsky E.
        • et al.
        A risk score to predict bleeding in patients with acute coronary syndromes.
        J Am Coll Cardiol. 2010; 55: 2556-2566
        • Czarny M.J.
        • Nathan A.S.
        • Yeh R.W.
        • Mauri L.
        Adherence to dual antiplatelet therapy after coronary stenting: a systematic review.
        Clin Cardiol. 2014; 37: 505-513
        • Bagai A.
        • Wang Y.
        • Wang T.Y.
        • et al.
        In-hospital switching between clopidogrel and prasugrel among patients with acute myocardial infarction treated with percutaneous coronary intervention: insights into contemporary practice from the national cardiovascular data registry.
        Circ Cardiovasc Interv. 2014; 7: 585-593
        • Baber U.
        • Dangas G.
        • Cohen D.J.
        • et al.
        Ticagrelor with aspirin or alone in high-risk patients after coronary intervention: rationale and design of the TWILIGHT study.
        Am Heart J. 2016; 182: 125-134
        • Vranckx P.
        • Valgimigli M.
        • Windecker S.
        • et al.
        Long-term ticagrelor monotherapy versus standard dual antiplatelet therapy followed by aspirin monotherapy in patients undergoing biolimus-eluting stent implantation: rationale and design of the GLOBAL LEADERS trial.
        EuroIntervention. 2016; 12: 1239-1245
        • Cuisset T.
        • Deharo P.
        • Quilici J.
        • et al.
        Benefit of switching dual antiplatelet therapy after acute coronary syndrome: the TOPIC (timing of platelet inhibition after acute coronary syndrome) randomized study.
        Eur Heart J. 2017; 38: 3070-3078
        • Sherwood M.W.
        • Wiviott S.D.
        • Peng S.A.
        • et al.
        Early clopidogrel versus prasugrel use among contemporary STEMI and NSTEMI patients in the US: insights from the National Cardiovascular Data Registry.
        J Am Heart Assoc. 2014; 3: e000849
        • Wiviott S.D.
        • Braunwald E.
        • Angiolillo D.J.
        • et al.
        Greater clinical benefit of more intensive oral antiplatelet therapy with prasugrel in patients with diabetes mellitus in the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-Thrombolysis in Myocardial Infarction 38.
        Circulation. 2008; 118: 1626-1636
        • Udell J.A.
        • Braunwald E.
        • Antman E.M.
        • et al.
        Prasugrel versus clopidogrel in patients with ST-segment elevation myocardial infarction according to timing of percutaneous coronary intervention: a TRITON-TIMI 38 subgroup analysis (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis In Myocardial Infarction 38).
        JACC Cardiovasc Interv. 2014; 7: 604-612
        • Angiolillo D.J.
        • Bernardo E.
        • Capodanno D.
        • et al.
        Impact of chronic kidney disease on platelet function profiles in diabetes mellitus patients with coronary artery disease taking dual antiplatelet therapy.
        J Am Coll Cardiol. 2010; 55: 1139-1146