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Similar Success Rates with Bivalirudin and Unfractionated Heparin in Bare-Metal Stent Implantation

Abstract

Background

Unfractionated heparin (UFH) is the traditional agent utilized during percutaneous peripheral interventions (PPIs) despite its well-known limitations. Bivalirudin, a thrombin-specific anticoagulant, overcomes many of the limitations of UFH and has consistently demonstrated comparable efficacy with significantly fewer bleeding complications. The purpose of this study was to compare procedural success in patients undergoing bare-metal stent implantation for atherosclerotic blockage of the renal, iliac, and femoral arteries and receiving either bivalirudin (0.75 mg/kg bolus/1.75 mg/kg/hr infusion) or UFH (50–70 U/kg/hr bolus) as the primary anticoagulant.

Methods

This study was an open-label, nonrandomized retrospective registry with the primary endpoint of procedural success. Secondary endpoints included incidence of: death, myocardial infarction (MI), urgent revascularization, amputation, and major and minor bleeding.

Results

One hundred and five consecutive patients were enrolled (bivalirudin = 53; heparin = 52). Baseline demographics were comparable between groups. Patients were pretreated with clopidogrel (approx. 71%) and aspirin (approx. 79%). Procedural success was achieved in 97% and 96% of patients in the bivalirudin- and heparin-treated groups, respectively. Event rates were low and similar between groups.

Conclusion

Bivalirudin maintained an equal rate of procedural success in this cohort without sacrificing patient safety. Results of this study add to the growing body of evidence supporting the safety and efficacy of bivalirudin as a possible substitute for UFH in anticoagulation during peripheral vascular bare-metal stent implantation.

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References

  1. Ouriel K (2001) Peripheral arterial disease. Lancet 358:1257–1264

    PubMed  Article  CAS  Google Scholar 

  2. Shammas NW, Dippel EJ (2005) Evidence-based management of peripheral vascular disease [review]. Curr Atheroscler Rep 7:358–363

    PubMed  Article  Google Scholar 

  3. Hirsh J, Warkentin TE, Raschke R, Granger C, Ohman EM, Dalen JE (1998) Heparin and low-molecular-weight heparin: Mechanisms of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest 114(5 Suppl):489S–510S

    PubMed  CAS  Google Scholar 

  4. Hirsh J (1991) Heparin. N Engl J Med 324:1565–1574

    PubMed  CAS  Article  Google Scholar 

  5. Bittl JA, Chaitman BR, Feit F, Kimball W, Topol EJ (2001) Bivalirudin versus heparin during coronary angioplasty for unstable or postinfarction angina: Final report reanalysis of the Bivalirudin Angioplasty Study. Am Heart J 142:952–959

    PubMed  Article  CAS  Google Scholar 

  6. Semba CP, Murphy TP, Bakal CW, Calis KA, Matalon TA (2000) Thrombolytic therapy with use of alteplase (rt-PA) in peripheral arterial occlusive disease: Review of the clinical literature. The Advisory Panel. J Vasc Interv Radiol 11:149–161

    PubMed  Article  CAS  Google Scholar 

  7. Lincoff AM, Kleiman NS, Kereiakes DJ, Feit F, Bittl JA, Jackman JD, Sarembock IJ, Cohen DJ, Spriggs D, Ebrahimi R, Keren G, Carr J, Cohen EA, Betriu A, Desmet W, Rutsch W, Wilcox RG, de Feyter PJ, Vahanian A, Topol EJ; REPLACE-2 Investigators (2004) Long-term efficacy of bivalirudin and provisional glycoprotein IIb/IIIa blockade vs heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary revascularization: REPLACE-2 randomized trial. JAMA 292:696–703

    PubMed  Article  CAS  Google Scholar 

  8. Henry TD (2002) Overcoming heparin limitations in high-risk percutaneous coronary intervention: The alternative strategy—replacing heparin with bivalirudin. J Invas Cardiol 14 (Suppl B):19–39

    Google Scholar 

  9. Chu WW, Kuchulakanti PK, Wang B, Torguson R, Clavijo C, Pichard AD, Suddath WO, Satler LF, Kent KM, Waksman R (2006) Bivalirudin versus unfractionated heparin in patients undergoing percutaneous coronary intervention after acute myocardial infarction. Cardiovasc Revasc Med 7:132–135

    PubMed  Article  Google Scholar 

  10. Yehudai L, Feit F (2006) Debate of adjunctive pharmacology for percutaneous coronary intervention: Thrombin inhibitors and clopidogrel are enough. J Interv Cardiol 19:464–469

    PubMed  Article  Google Scholar 

  11. Allie DE, Lirtzman MD, Wyatt CH, Keller VA, Khan MH, Khan MA, Fail PS, Hebert CJ, Ellis SD, Mitran E, Chaisson G, Stagg S Jr, Allie AA, Walker CM (2003) Bivalirudin as a foundation anticoagulant in peripheral vascular disease: A safe and feasible alternative for renal and iliac interventions. J Invas Cardiol 15:334–342

    Google Scholar 

  12. Rundback J, Sacks D, Kent C, Cooper C, Jones D, Morphy T, Rosenfield K, White C, Bettmann M, Cortell S, Pushett J, Clair D, Cole P for the American Councils on Cardiovascular Radiology, High Blood Pressure Research, Kidney in Cardiovascular Disease, Cardio-Thoracic and Vascular Surgery, and Clinical Cardiology, and the Society for Interventional Radiology FDA Device Forum Committee (2002) Guidelines for the reporting of renal artery revascularization in clinical trials. Circulation 106:1572–1585

  13. Technology Assessment Committee (1997) Reporting standards for clinical evaluation of new peripheral arterial revascularization devices. J Vasc Interv Radiol 8:137–149

    Article  Google Scholar 

  14. Rajan DK, Patel NH, Valji K, Cardella JF, Bakal C, et al (2005) Quality improvement guidelines for percutaneous management of acute limb ischemia. J Vasc Interv Radiol 16:585–595

    PubMed  Google Scholar 

  15. Bovill EG, Terrin ML, Stump DC, et al (1991) Hemorrhagic events during therapy with recombinant tissue-type plasminogen activator, heparin, and aspirin for acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI), Phase II Trial. Ann Intern Med 115:256–265

    PubMed  CAS  Google Scholar 

  16. Mascelli MA, Kleiman NS, Marciniak SJ Jr, Damaraju L, Weisman HF, Jordan RE (2000) Therapeutic heparin concentrations augment platelet reactivity: Implications for the pharmacologic assessment of the glycoprotein IIb/IIIa antagonist abciximab. Am Heart J 139:696–703

    PubMed  Article  CAS  Google Scholar 

  17. Sobel M, Fish WR, Toma N, Luo S, Bird K, Mori K, Kusumoto S, Blystone SD, Suda Y (2001) Heparin modulates integrin function in human platelets. J Vasc Surg 33:587–594

    PubMed  Article  CAS  Google Scholar 

  18. Xiao Z, Theroux P (1998) Platelet activation with UFH at therapeutic concentrations and comparisons with a low-molecular-weight heparin and with a direct thrombin inhibitor. Circulation 97:251–256

    PubMed  CAS  Google Scholar 

  19. Barzu T, Molho P, Tobelem G, Petitou M, Caen J (1985) Binding and endocytosis of heparin by human endothelial cells in culture. Biochim Biophys Acta 845:196–203

    PubMed  Article  CAS  Google Scholar 

  20. Young E, Prins M, Levine MN, Hirsh J (1992) Heparin binding to plasma proteins, an important mechanism for heparin resistance. Thromb Haemost 67:639–643

    PubMed  CAS  Google Scholar 

  21. Kelton JG, Warkentin TE (1998) Heparin-induced thrombocytopenia: Diagnosis, natural history and treatment options. Postgrad Med 103:169–178

    PubMed  CAS  Article  Google Scholar 

  22. Moen MD, Keating GM, Wellington K (2005) Bivalirudin: A review of its use in patients undergoing percutaneous coronary intervention. Drugs 65:1869–1891

    PubMed  Article  CAS  Google Scholar 

  23. Allie DE, Hebert CJ, Lirtzman MD, Wyatt CH, Keller VA, Khan MH, Khan MA, Fail PS, Vivekananthan K, Allie SE, Mitran EV, Chaisson G, Stagg SJ 3rd, Allie AA, McElderry MW, Barker EA, Walker CM (2005) A safety and feasibility report of combined direct thrombin and GP IIb/IIIa inhibition with bivalirudin and tirofiban in peripheral vascular disease intervention: Treating critical limb ischemia like acute coronary syndrome. J Invas Cardiol 17:427–432

    Google Scholar 

  24. Ebrahimi R, Lincoff AM, Bittl JA, Chew D, Wolski K, Wadhan N, Toggart EJ, Topol EJ (2005) Bivalirudin vs heparin in percutaneous coronary intervention: A pooled analysis. J Cardiovasc Pharmacol Ther 10:209–216

    PubMed  Article  CAS  Google Scholar 

  25. Lincoff AM, Bittl JA, Kleiman NS, Sarembock IJ, Jackman JD, Mehta S, Tannenbaum MA, Niederman AL, Bachinsky WB, Tift-Mann J 3rd, Parker HG, Kereiakes DJ, Harrington RA, Feit F, Maierson ES, Chew DP, Topol EJ; REPLACE-1 Investigators (2004) Comparison of bivalirudin versus heparin during percutaneous coronary intervention (the Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events [REPLACE]-1 trial). Am J Cardiol 93:1092–1096

    PubMed  Article  CAS  Google Scholar 

  26. Hillegass WB (2005) PCI with bivalirudin and provisional GP IIb/IIIa inhibition is more cost-effective than heparin plus routine GP IIb/IIIa inhibition. Commentary. Evid Based Cardiovasc Med 9:68–71

    Article  Google Scholar 

  27. Chew DP, Lincoff AM, Gurm H, Wolski K, Cohen DJ, Henry T, Feit F, Topol EJ; REPLACE-2 Investigators (2005) Bivalirudin versus heparin and glycoprotein IIb/IIIa inhibition among patients with renal impairment undergoing percutaneous coronary intervention (a subanalysis of the REPLACE-2 trial). Am J Cardiol 95:581–585

    PubMed  Article  CAS  Google Scholar 

  28. Gurm HS, Sarembock IJ, Kereiakes DJ, Young JJ, Harrington RA, Kleiman N, Feit F, Wolski K, Bittl JA, Wilcox R, Topol EJ, Lincoff AM (2005) Use of bivalirudin during percutaneous coronary intervention in patients with diabetes mellitus: An analysis from the randomized evaluation in percutaneous coronary intervention linking angiomax to reduced clinical events (REPLACE)-2 trial. J Am Coll Cardiol 45:1932–1938

    PubMed  Article  CAS  Google Scholar 

  29. Yegin A, Corrigan VE, Lembo NJ, Knapp WS, Bernstein C, Chronos NA, Knopf WD (2002) Bivalirudin anticoagulation is safe and feasible in elective percutaneous intervention for peripheral arterial disease. Atlanta, GA: American Cardiovascular Research Institute (ACRI), Atlanta Cardiology Group

  30. Katzen BT, Ardid MI, MacLean AA, Kovacs MF, Zemel G, Benenati JF, Powell A, Samuels S (2005) Bivalirudin as an anticoagulation agent: Safety and efficacy in peripheral interventions. J Vasc Interv Radiol 16:1183–1187; quiz 1187

    PubMed  Google Scholar 

  31. Shammas NW, Allie D, Hall P, Young J, Laird J, Safian R, Virmani A; APPROVE Investigators (2005) Predictors of in-hospital and 30-day complications of peripheral vascular interventions using bivalirudin as the primary anticoagulant: Results from the APPROVE Registry. J Invas Cardiol 17:356–359

  32. Shammas NW, Lemke JH, Dippel EJ, McKinney DE, Takes VS, Youngblut M, Harris M, Harb C, Kapalis MJ, Holden J (2003) In-hospital complications of peripheral vascular interventions using unfractionated heparin as the primary anticoagulant. J Invas Cardiol 15:242–246

    Google Scholar 

  33. Ormiston JA, Shaw BL, Panther MJ, Ruygrok PN, Davlin GP, Stewart RAH, Webster MWI (2002) Percutaneous coronary intervention with bivalirudin anticoagulation, immediate sheath removal, and early ambulation: A feasibility study with implications for day-stay procedures. Catheter Cardiovasc Interv 55:289–293

    PubMed  Article  Google Scholar 

  34. Chacko M, Lincoff MA, Wolski KE, Cohen DJ, Bittl JA, Lansky AJ, Tsuchiya Y, Betriu A, Yen M, Chew DP, Cho L, Topol EJ (2006) Ischemic and bleeding outcomes in women treated with bivalirudin during percutaneous coronary intervention: A subgroup analysis of the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)–2 trial. Am Heart J 151:1032.e1–1032.e7

    Article  Google Scholar 

  35. Koster A, Spiess B, Jurmann M, Dyke CM, Sedira NG, Aronson S, Lincoff M (2006) Bivalirudin provides rapid, effective and reliable anticoagulation during off-pump coronary revascularization: Results of the “EVOLUTION OFF” trial [cardiovascular anesthesia]. Anesth Analg 103:540–544

    PubMed  Article  CAS  Google Scholar 

  36. Sorin BJ, Moliterno DJ, Lincoff MA, Steinhubl SR, Wolski KE, Topol EJ (2004) Relationship between activated clotting time and ischemic or hemorrhagic complications. Circulation 100:994–998

    Google Scholar 

  37. Package Insert Angiomax TMC PN 1002-5 (11/12/03)

  38. Patel N, Sacks D, Patel RI, Moresco KP, Ouriel K, Gray R, Ambrosius WT, Lewis CA, the members of the Society of Interventional Radiology Technology Assessment Committee (2003) SIR reporting standards for the treatment of acute limb ischemia with use of transluminal removal of arterial thrombus. J Vasc Interv Radiol 14:S453–S4654

    PubMed  Google Scholar 

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Acknowledgments

D.L. has an unrestricted grant from The Medicines Company.

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Correspondence to Bernardo J. Reyes.

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Hallak, O., Shams, S.A., Broce, M. et al. Similar Success Rates with Bivalirudin and Unfractionated Heparin in Bare-Metal Stent Implantation. Cardiovasc Intervent Radiol 30, 906–911 (2007). https://doi.org/10.1007/s00270-007-9038-1

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  • DOI: https://doi.org/10.1007/s00270-007-9038-1

Keywords

  • Anticoagulation
  • Bivalirudin
  • Heparin
  • Interventional Radiology
  • Peripheral Interventions