Download PDF
Thromb Haemost 2008; 99(03): 487-493
DOI: 10.1160/TH07-11-0680
Theme Issue Article
Schattauer GmbH

Individualized antithrombotic therapy in high risk patients after coronary stenting. A double-edged sword between thrombosis and bleeding

Andreas E. May
1   Medizinische Klinik III (Kardiologie und Kreislauferkrankungen), Eberhard Karls Universität, Tübingen, Germany
,
Tobias Geisler
1   Medizinische Klinik III (Kardiologie und Kreislauferkrankungen), Eberhard Karls Universität, Tübingen, Germany
,
Meinrad Gawaz
1   Medizinische Klinik III (Kardiologie und Kreislauferkrankungen), Eberhard Karls Universität, Tübingen, Germany
› Author Affiliations
Further Information

Publication History

Received: 16 November 2007

Accepted after major revision: 10 January 2008

Publication Date:
07 December 2017 (online)

    Permissions and Reprints

Summary

Dual antiplatelet therapy with aspirin and clopidogrel is currently the standard therapy after coronary stent implantation to prevent a life-threatening stent thrombosis. However, a variety of procedural and individual factors contribute to the individual patient risk and have to be taken into account to allow for an individual recommendation for both the duration and intensity of the antiplatelet therapy. Obviously, the benefit of the prevention of stent thrombosis by antithrombotic therapy has to outweigh the risk of severe bleeding complications. Depending on the individual clinical situation and procedural characteristics (stent type, length, angiographic result etc.), the recommended duration of the combined antiplatelet therapy currently varies from four weeks to at least one year.These recommendations are mainly based on large, prospective, randomized trials and evidence-based guidelines. However, in a subgroup of high-risk patients there is insufficient evidence for the benefit of conventional dual antiplatelet regimen.These include i) patients with an indication for anticoagulation, ii) patients with urgent need for an operation requiring a perioperative withholding of antiplatelet therapy, as well as iii) clopidogrel low responders.This review aims to provide a stratification to define patient collectives who may benefit from more individualized antithrombotic regimens on behalf of currently available literature and guidelines.

Keywords

Antiplatelet agents - antiplatelet drugs - clinical trials - atherothrombosis - atherosclerosis - acute myocardial infarction
 

  • References

  • 1 Grines CL, Bonow RO, Casey DE. et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: A science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. J Am Coll Cardiol 2007; 49: 734-739.
    CrossrefPubMedGoogle Scholar
  • 2 Silber S, Borggrefe M, Böhm M. et al. Positionspapier der DGK zur Wirksamkeit und Sicherheit von Medikamente freisetzenden Koronarstents (DES). Kardiologe 2007; 1: 84-111.
    CrossrefPubMedGoogle Scholar
  • 3 Smith SC, Jr Feldman TE, Hirshfeld JW. Jr et al. American College of Cardiology/American Heart Association Task Force on Practice Guidelines; ACC/ AHA/SCAI Writing Committee to Update 2001 Guidelines for Percutaneous Coronary Intervention. ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update 2001 Guidelines for Percutaneous Coronary Intervention). Circulation 2006; 113: e166-286.
    CrossrefPubMedGoogle Scholar
  • 4 Bassand J-P, Hamm CW, Ardissino D. et al. Guidelines for the diagnosis and treatment of non-ST-segment elevation in acute coronary syndromes. Eur Heart J 2007; 28: 1598-1660.
    CrossrefPubMedGoogle Scholar
  • 5 Verheugt FWA. Good old warfarin for stroke prevention in atrial fibrillation. Lancet 2006; 367: 1877-1878.
    CrossrefPubMedGoogle Scholar
  • 6 The ACTVE W Writing group on behalf of the ACTIVE Investigators. Clopidogrel versus aspirin versus anticoagulation for atrial fibrillation in the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events (ACTIVE W): A randomised trial. Lancet 2006; 367: 1903-1912.
    CrossrefPubMedGoogle Scholar
  • 7 Rubboli A, Pasquale G. Optimal antithrombotic treatment in patients with an indication for long-term anticoagulation undergoing coronary artery stenting. Future Cardiol 2006; 2: 205-213.
    CrossrefPubMedGoogle Scholar
  • 8 Schomig A, Neumann FJ, Kastrati A. et al. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med 1996; 334: 1084-1089.
    CrossrefPubMedGoogle Scholar
  • 9 Leon MB, Baim DS, Popma JJ. et al. A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting. Stent Anticoagulation Restenosis Study Investigators. N Engl J Med 1998; 339: 1665-1671.
    CrossrefPubMedGoogle Scholar
  • 10 Bertrand ME, Legrand V, Boland J. et al. Randomized multicenter comparison of conventional anticoagulation versus antiplatelet therapy in unplanned and elective coronary stenting. The full anticoagulation versus aspirin and ticlopidine (fantastic) study. Circulation 1998; 98: 1597-1603.
    CrossrefPubMedGoogle Scholar
  • 11 Karjalainen PP, Porela P, Ylitalo A. et al. Safety and efficacy of combined antiplatelet-warfarin therapy after coronary stenting. Eur Heart J 2007; 28: 726-732.
    CrossrefPubMedGoogle Scholar
  • 12 Kuchulakanti PK, Chu WW, Torguson R. et al. Correlates and long-term outcomes of angiographically proven stent thrombosis with sirolimus- and paclitaxeleluting stents. Circulation 2006; 113: 1108-1113.
    CrossrefPubMedGoogle Scholar
  • 13 Fuster V, Ryden LE, Cannom DS. et al. ACC/AHA/ ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation. Circulation 2006; 114: e257-354.
    CrossrefPubMedGoogle Scholar
  • 14 Gage BF, Van Walraven C, Pearce L. et al. Selecting patients with atrial fibrillation for anticoagulation: stroke risk stratification in patients taking aspirin. Circulation 2004; 110: 2287-2292.
    CrossrefPubMedGoogle Scholar
  • 15 Rubboli A, Milandri M, Castelvetri C. et al. Metaanalysis of trials comparing oral anticoagulation and aspirin versus dual antiplatelet therapy after coronary stenting. Clues for the management of patients with an indication for long-term anticoagulation undergoing coronary stenting. Cardiology 2005; 104: 101-106.
    CrossrefPubMedGoogle Scholar
  • 16 Porter A, Konstantino Y, Iakobishvili Z. et al. Shortterm triple therapy with aspirin, warfarin, and a thienopyridine among patients undergoing percutaneous coronary intervention. Catheter Cardiovasc Interv 2006; 68: 56-61.
    CrossrefPubMedGoogle Scholar
  • 17 Khurram Z, Chou E, Minutello R. et al. Combination therapy with aspirin, clopidogrel and warfarin following coronary stenting is associated with a significant risk of bleeding. J Invasive Cardiol 2006; 18: 162-164.
    PubMedGoogle Scholar
  • 18 Buresly K, Eisenberg MJ, Zhang X. et al. Bleeding complications associated with combinations of aspirin, thienopyridine derivatives, and warfarin in elderly patients following acute myocardial infarction. Arch Intern Med 2005; 165: 784-789.
    CrossrefPubMedGoogle Scholar
  • 19 Orford JL, Fasseas P, Melby S. et al. Safety and efficacy of aspirin, clopidogrel, and warfarin after coronary stent placement in patients with an indication for anticoagulation. Am Heart J 2004; 147: 463-467.
    CrossrefPubMedGoogle Scholar
  • 20 Konstantino Y, Iakobishvili Z, Porter A. et al. Aspirin, warfarin and a thienopyridine for acute coronary syndromes. Cardiology 2006; 105: 80-85.
    CrossrefPubMedGoogle Scholar
  • 21 Rao AK, Pratt C, Berke A. et al. Thrombolysis in Myocardial Infarction (TIMI) Trial-Phase I: hemorrhagic manifestations and changes in plasma fibrinogen and the fibrinolytic system in patients treated with recombinant tissue plasminogen activator and streptokinase. J Am Coll Cardiol 1988; 11: 1-11.
    CrossrefPubMedGoogle Scholar
  • 22 Hurlen M, Abdelnoor M, Smith P. et al. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med 2002; 347: 969-974.
    CrossrefPubMedGoogle Scholar
  • 23 Andreotti F, Testa L, Biondi-Zoccai GG. et al. Aspirin plus warfarin compared to aspirin alone after acute coronary syndromes: an updated and comprehensive meta-analysis of 25,307 patients. Eur Heart J 2006; 27: 519-526
    CrossrefPubMedGoogle Scholar
  • 24 Iakovou I, Schmidt T, Bonizzoni E. et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. J Am Med Assoc 2005; 293: 2126-2130.
    CrossrefPubMedGoogle Scholar
  • 25 Patrono C, Garcia Rodriguez LA, Landolfi R. et al. Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med 2005; 353: 2373-2383.
    CrossrefPubMedGoogle Scholar
  • 26 Kaluza GL, Joseph J, Lee JR. et al. Catastrophic outcomes of noncardiac surgery soon after coronary stenting. J Am Coll Cardiol 2000; 35: 1288-1294.
    CrossrefPubMedGoogle Scholar
  • 27 Vicenzi MN, Meislitzer T, Heitzinger B. et al. Coronary artery stenting and non-cardiac surgery: a prospective outcome study. Br J Anaesth 2006; 96: 686-693.
    CrossrefPubMedGoogle Scholar
  • 28 Wilson SH, Fasseas P, Orford JL. et al. Clinical outcome of patients undergoing non-cardiac surgery in the two months following coronary stenting. J Am Coll Cardiol 2003; 42: 234-240.
    CrossrefPubMedGoogle Scholar
  • 29 Riddell JW, Chiche L, Plaud B. et al. Coronary stents and noncardiac surgery. Circulation 2007; 116: e378-e382.
    CrossrefPubMedGoogle Scholar
  • 30 Brilakis ES, Banerjee S, Berger PB. Perioperative management of patients with coronary stents. J Am Coll Cardiol 2007; 49: 2145-2150.
    CrossrefPubMedGoogle Scholar
  • 31 Broad L, Lee T, Conroy M. et al. Successful management of patients with a drug-eluting coronary stent presenting for elective, noncardiac surgery. Br J Anaesth 2007; 98: 19-22.
    CrossrefPubMedGoogle Scholar
  • 32 Neumann F-J, Gawaz M, Ott I. et al. Prospective evaluation of hemostatic predictors of subacute stent thrombosis after coronary Palmaz-Schatz stenting. J Am Coll Card 1996; 27: 15-21.
    PubMedGoogle Scholar
  • 33 Gawaz M, Neumann F-J, Ott I. et al. Role of activation- dependent platelet membrane glycoproteins in development of subacute occlusive coronary stent thrombosis. Coronary Artery Dis 1997; 8: 121-128.
    CrossrefPubMedGoogle Scholar
  • 34 Gawaz M, Langer H, May AE. Platelets in inflammation and atherothrombosis. J Clin Invest 2005; 115: 3378-3384.
    CrossrefPubMedGoogle Scholar
  • 35 Muller I, Besta F, Schulz C. et al. Prevalence of clopidogrel non-responders among patients with stable angina pectoris scheduled for elective coronary stent placement. Thromb Haemost 2003; 89: 783-787.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 36 Serebruany VL, Steinhubl SR, Berger PB. et al. Variability in platelet responsiveness to clopidogrel among 544 individuals. J Am Coll Cardiol 2005; 45: 246-251.
    CrossrefPubMedGoogle Scholar
  • 37 Gurbel PA, Bliden KP, Hiatt BL. et al. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation 2003; 107: 2908-2913.
    CrossrefPubMedGoogle Scholar
  • 38 Gurbel PA, Bliden KP, Guyer K. et al. Platelet reactivity in patients and recurrent events post-stenting: results of the PREPARE POST-STENTING Study. J Am Coll Cardiol 2005; 46: 1820-1826.
    CrossrefPubMedGoogle Scholar
  • 39 Geisler T, Langer H, Wydymus M. et al. Low response to clopidogrel is associated with cardiovascular outcome after coronary stent implantation. Eur Heart J 2006; 27: 2420-2425.
    CrossrefPubMedGoogle Scholar
  • 40 Hochholzer W, Trenk D, Bestehorn HP. et al. Impact of the degree of peri-interventional platelet inhibition after loading with clopidogrel on early clinical outcome of elective coronary stent placement. J Am Coll Cardiol 2006; 48: 1742-1750.
    CrossrefPubMedGoogle Scholar
  • 41 Wenaweser P, Dorffler-Melly J, Imboden K. et al. Stent thrombosis is associated with an impaired response to antiplatelet therapy. J Am Coll Cardiol 2005; 45: 1748-1752.
    CrossrefPubMedGoogle Scholar
  • 42 Geisler T, Graß D, Bigalke B. et al. The PREDICT (residual platelet aggregation after deployment of intracoronary stent)-score. J Thromb Haemost. 2007 Epub ahead of print.
    PubMedGoogle Scholar
  • 43 Matetzky S, Shenkman B, Guetta V. et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation 2004; 109: 3171-3175.
    CrossrefPubMedGoogle Scholar
  • 44 Buonamici P, Marcucci R, Migliorini A. et al. Impact of platelet reactivity after clopidogrel administration on drug-eluting stent thrombosis. J Am Coll Cardiol 2007; 49: 2312-2317.
    CrossrefPubMedGoogle Scholar
  • 45 von Beckerath N, Taubert D, Pogatsa-Murray G. et al. Absorption, metabolization, and antiplatelet effects of 300-, 600-, and 900-mg loading doses of clopidogrel: results of the ISAR-CHOICE (Intracoronary Stenting and Antithrombotic Regimen: Choose Between 3 High Oral Doses for Immediate Clopidogrel Effect) Trial. Circulation 2005; 112: 2946-2950.
    CrossrefPubMedGoogle Scholar
  • 46 Montalescot G, Sideris G, Meuleman C. et al. ; ALBION Trial Investigators. A randomized comparison of high clopidogrel loading doses in patients with non-STsegment elevation acute coronary syndromes: the ALBION (Assessment of the Best Loading Dose of Clopidogrel to Blunt Platelet Activation, Inflammation and Ongoing Necrosis) trial. J Am Coll Cardiol 2006; 48: 931-938.
    CrossrefPubMedGoogle Scholar
  • 47 Angiolillo DJ, Shoemaker SB, Desai B. et al. Randomized comparison of a high clopidogrel maintenance dose in patients with diabetes mellitus and coronary artery disease. Results of the Optimizing Antiplatelet Therapy in Diabetes Mellitus (OPTIMUS) Study. Circulation 2007; 115: 708-716.
    CrossrefPubMedGoogle Scholar
  • 48 von Beckerath N, Kastrati A, Wieczorek A. et al. A double-blind, randomized study on platelet aggregation in patients treated with a daily dose of 150 or 75 mg of clopidogrel for 30 days. Eur Heart J 2007; 15: 1814-1819.
    PubMedGoogle Scholar
  • 49 Campo G, Valgimigli M, Gemmati D. et al. Poor responsiveness to clopidogrel: drug-specific or class-effect mechanism? Evidence from a clopidogrel-to-ticlopidine crossover study. J Am Coll Cardiol 2007; 50: 1132-1137.
    CrossrefPubMedGoogle Scholar
  • 50 Wiviott SD, Braunwald E, McCabe CH. et al. the TRITON–TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007 Epub ahead of print.
    PubMedGoogle Scholar