Background: Clopidogrel use as single antiplatelet therapy (SAPT) has never been evaluated in stable coronary artery disease (CAD) outpatients either as compared to placebo or aspirin. Methods: We therefore studied 2,823 outpatients included in a prospective registry. The patients were divided into 2 groups according to their antiplatelet therapy regimen: patients treated with clopidogrel were compared with those treated with aspirin alone. Results: The mean time since CAD diagnosis was 7.9 years. Altogether, 776 (27.5%) patients received clopidogrel as SAPT. Factors independently associated with clopidogrel use were prior aortic or peripheral intervention, drug-eluting stent implantation, stroke, carotid endarterectomy and time since CAD diagnosis. Clopidogrel tended to be used in higher-risk patients: composite of cardiovascular death, myocardial infarction or stroke at 5.8 versus 4.2% (p = 0.056). However, after propensity score matching, similar event rates were observed between the groups: 5.9% when treated with clopidogrel versus 4.4% with aspirin (p = 0.207). The rate of bleeding was also similar between the groups. Conclusions: Our study shows that a significant proportion of stable CAD patients are treated with clopidogrel as SAPT in modern practice. Several correlates of such an attitude were identified. Our results suggest that this strategy is not beneficial as compared to aspirin alone in terms of ischaemic or bleeding events.

1.
Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, Buring J, Hennekens C, Kearney P, Meade T, Patrono C, Roncaglioni MC, Zanchetti A: Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009;373:1849-1860.
2.
Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324:71-86.
3.
Montalescot G, Sechtem U, Achenbach S, et al: 2013 ESC guidelines on the management of stable coronary artery disease: The Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J 2013;34:2949-3003.
4.
Fihn SD, Blankenship JC, Alexander KP, Bittl JA, Byrne JG, Fletcher BJ, Fonarow GC, Lange RA, Levine GN, Maddox TM, Naidu SS, Ohman EM, Smith PK: 2014 ACC/AHA/AATS/PCNA/SCAI/STS focused update of the guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, and the American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2014;64:1929-1949.
5.
Delsart P, Lemesle G, Lamblin N, Tricot O, Meurice T, Mycinski C, Elkohen M, Chmait A, Haulon S, Bauters C: Secondary medical prevention and clinical outcome in coronary artery disease patients with a history of non-coronary vascular intervention: a report from the CORONOR investigators. Eur J Prev Cardiol 2015;22:864-871.
6.
Lemesle G, Bauters A, Bauters C: Antithrombotic therapy in diabetic patients with coronary artery disease. Panminerva Med 2015;57:87-99.
7.
Manchuelle A, Delhaye C, Schurtz G, Sudre A, Hurt C, Bonello L, Puymirat E, Bauters C, Lemesle G: Dual antiplatelet therapy in patients with a long coronary artery lesion over 30 mm: determinants and impact on prognosis. Arch Cardiovasc Dis 2015;108:235-243.
8.
Sudlow CL, Mason G, Maurice JB, Wedderburn CJ, Hankey GJ: Thienopyridine derivatives versus aspirin for preventing stroke and other serious vascular events in high vascular risk patients. Cochrane Database Syst Rev 2009;4:CD001246.
9.
Bonaca MP, Bhatt DL, Cohen M, Steg PG, Storey RF, Jensen EC, Magnani G, Bansilal S, Fish MP, Im K, Bengtsson O, Oude Ophuis T, Budaj A, Theroux P, Ruda M, Hamm C, Goto S, Spinar J, Nicolau JC, Kiss RG, Murphy SA, Wiviott SD, Held P, Braunwald E, Sabatine MS: Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med 2015;372:1791-1800.
10.
Mauri L, Kereiakes DJ, Yeh RW, Driscoll- Shempp P, Cutlip DE, Steg PG, Normand SL, Braunwald E, Wiviott SD, Cohen DJ, Holmes DR Jr, Krucoff MW, Hermiller J, Dauerman HL, Simon DI, Kandzari DE, Garratt KN, Lee DP, Pow TK, Ver Lee P, Rinaldi MJ, Massaro JM: Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med 2014;371:2155-2166.
11.
Gurbel PA, Bliden KP, DiChiara J, Newcomer J, Weng W, Neerchal NK, Gesheff T, Chaganti SK, Etherington A, Tantry US: Evaluation of dose-related effects of aspirin on platelet function: results from the Aspirin-Induced Platelet Effect (ASPECT) study. Circulation 2007;115:3156-3164.
12.
Michelson AD, Cattaneo M, Eikelboom JW, Gurbel P, Kottke-Marchant K, Kunicki TJ, Pulcinelli FM, Cerletti C, Rao AK: Aspirin resistance: position paper of the Working Group on Aspirin Resistance. J Thromb Haemost 2005;3:1309-1311.
13.
Dillinger JG, Drissa A, Sideris G, Bal dit Sollier C, Voicu S, Manzo Silberman S, Logeart D, Drouet L, Henry P: Biological efficacy of twice daily aspirin in type 2 diabetic patients with coronary artery disease. Am Heart J 2012;164:600-606.e601.
14.
Dillinger JG, Sideris G, Henry P, Bal dit Sollier C, Ronez E, Drouet L: Twice daily aspirin to improve biological aspirin efficacy in patients with essential thrombocythemia. Thromb Res 2012;129:91-94.
15.
Henry P, Vermillet A, Boval B, Guyetand C, Petroni T, Dillinger JG, Sideris G, Sollier CB, Drouet L: 24-h time-dependent aspirin efficacy in patients with stable coronary artery disease. Thromb Haemost 2011;105:336-344.
16.
A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE) - CAPRIE Steering Committee. Lancet 1996;348:1329-1339.
17.
Bauters C, Deneve M, Tricot O, Meurice T, Lamblin N: Prognosis of patients with stable coronary artery disease (from the CORONOR study). Am J Cardiol 2014;113:1142-1145.
18.
Hamon M, Lemesle G, Tricot O, Meurice T, Deneve M, Dujardin X, Brufau JM, Bera J, Lamblin N, Bauters C: Incidence, source, determinants, and prognostic impact of major bleeding in outpatients with stable coronary artery disease. J Am Coll Cardiol 2014;64:1430-1436.
19.
Lemesle G, Lamblin N, Meurice T, Tricot O, Lallemant R, Nugue O, Delomez M, Equine O, Tondeux S, Bauters C: Dual antiplatelet therapy in patients with stable coronary artery disease in modern practice: prevalence, correlates, and impact on prognosis (from the Suivi d'une cohorte de patients COROnariens stables en region NORd-Pas-de-Calais study). Am Heart J 2014;168:479-486.
20.
Lemesle G, Paparoni F, Delhaye C, Bonello L, Lablanche JM: Duration of dual antiplatelet therapy after percutaneous coronary intervention with drug-eluting stent implantation: a review of the current guidelines and literature. Hosp Pract 2011;39:32-40.
21.
Lemesle G, Torguson R, Bonello L, de Labriolle A, Maluenda G, Ben-Dor I, Collins SD, Syed AI, Xue Z, Satler LF, Pichard AD, Waksman R: Relation between clopidogrel discontinuation and early cardiovascular events after percutaneous coronary intervention with drug-eluting stents. EuroIntervention 2011;6:1053-1059.
22.
Wenaweser P, Daemen J, Zwahlen M, van Domburg R, Juni P, Vaina S, Hellige G, Tsuchida K, Morger C, Boersma E, Kukreja N, Meier B, Serruys PW, Windecker S: Incidence and correlates of drug-eluting stent thrombosis in routine clinical practice: 4-year results from a large 2-institutional cohort study. J Am Coll Cardiol 2008;52:1134-1140.
23.
Daemen J, Wenaweser P, Tsuchida K, Abrecht L, Vaina S, Morger C, Kukreja N, Juni P, Sianos G, Hellige G, van Domburg RT, Hess OM, Boersma E, Meier B, Windecker S, Serruys PW: Early and late coronary stent thrombosis of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice: data from a large two-institutional cohort study. Lancet 2007;369:667-678.
24.
Garcia Rodriguez LA, Lin KJ, Hernandez-Diaz S, Johansson S: Risk of upper gastrointestinal bleeding with low-dose acetylsalicylic acid alone and in combination with clopidogrel and other medications. Circulation 2011;123:1108-1115.
25.
Lin KJ, De Caterina R, Garcia Rodriguez LA: Low-dose aspirin and upper gastrointestinal bleeding in primary versus secondary cardiovascular prevention: a population-based, nested case-control study. Circ Cardiovasc Qual Outcomes 2014;7:70-77.
26.
Jolly SS, Pogue J, Haladyn K, Peters RJ, Fox KA, Avezum A, Gersh BJ, Rupprecht HJ, Yusuf S, Mehta SR: Effects of aspirin dose on ischaemic events and bleeding after percutaneous coronary intervention: insights from the PCI-CURE study. Eur Heart J 2009;30:900-907.
27.
Peters RJ, Mehta SR, Fox KA, Zhao F, Lewis BS, Kopecky SL, Diaz R, Commerford PJ, Valentin V, Yusuf S: Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes: observations from the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) study. Circulation 2003;108:1682-1687.
28.
Bhatt DL, Hirsch AT, Ringleb PA, Hacke W, Topol EJ: Reduction in the need for hospitalization for recurrent ischemic events and bleeding with clopidogrel instead of aspirin. Am Heart J 2000;140:67-73.
29.
Hansen ML, Sorensen R, Clausen MT, Fog-Petersen ML, Raunso J, Gadsboll N, Gislason GH, Folke F, Andersen SS, Schramm TK, Abildstrom SZ, Poulsen HE, Kober L, Torp-Pedersen C: Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med 2010;170:1433-1441.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.