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Initial Experience With Ticagrelor in Patients With Critical Limb Ischemia and High On-Clopidogrel Platelet Reactivity Undergoing Complex Peripheral Endovascular Procedures

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Abstract

Purpose

To investigate the safety and efficacy of ticagrelor in patients with critical limb ischemia (CLI) and high on-clopidogrel platelet reactivity (HCPR) undergoing complex, limb-salvage, peripheral endovascular procedures (PEP).

Materials and Methods

The study included consecutive patients with HCPR undergoing PEP for CLI. HCPR was defined as platelet reaction units (PRU) >234 as assessed by the VerifyNow P2Y12 assay. Patients with HCPR were prescribed ticagrelor, 180/90 mg twice daily, and aspirin, 100 mg daily, for 6 months and ticagrelor, 180/90 mg twice daily, thereafter. Primary safety outcome was total major bleeding, and primary efficacy outcome was the composite of cardiovascular death and major amputation. Secondary outcomes included the level of platelet inhibition achieved and target limb revascularization (TLR)-free survival rate.

Results

In total, 37 CLI patients with 40 limbs were investigated. Mean follow-up period was 11.3 ± 5.0 months (range 6–21). The mean treated lesion length was 229.2 ± 71.4 mm in the femoropopliteal axis and 179.3 ± 83.9 mm in the infrapopliteal arteries. No major or minor bleeding was detected. There were four periprocedural minor adverse events (10.8 %), and in two cases (5.6 %) ticagrelor was discontinued. In all patients, ticagrelor achieved platelet inhibition lower than the cut-off value. Mean PRU during clopidogrel therapy was 308.4 ± 41.8 (range 257–422) versus 67.0 ± 52.8 (range 2–189) when switched to ticagrelor; p < 0.0001. Kaplan–Meier estimated primary efficacy outcome and TLR-free survival rates were 92.0 and 67.3 % at 12 months, respectively.

Conclusion

In this series of CLI patients with HCPR undergoing complex PEP, initial experience with ticagrelor was proven safe and efficient because it resulted in sufficient platelet inhibition and satisfactory clinical results without major complications.

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References

  1. Rooke TW, Hirsch AT, Misra S et al (2013) Management of patients with peripheral artery disease (compilation of 2005 and 2011 ACCF/AHA Guideline Recommendations): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 61(14):1555–1570

    Article  PubMed  Google Scholar 

  2. Ziegler-Graham K, MacKenzie EJ, Ephraim PL, Travison TG, Brookmeyer R (2008) Estimating the prevalence of limb loss in the United States: 2005 to 2050. Arch Phys Med Rehabil 89(3):422–429

    Article  PubMed  Google Scholar 

  3. Holdsworth RJ, McCollum PT (1997) Results and resource implications of treating end-stage limb ischaemia. Eur J Endovasc Surg 13:164–173

    Article  CAS  Google Scholar 

  4. Dorros G, Jaff MR, Dorros AM, Mathiak LM, He T (2001) Tibioperoneal (outflow lesion) angioplasty can be used as primary treatment in 235 patients with critical limb ischemia: Five-year follow-up. Circulation 104(17):2057–2062

    Article  CAS  PubMed  Google Scholar 

  5. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG, TASC II Working Group (2007) Inter-society consensus for the management of peripheral arterial disease (TASCII). Eur J Vasc Endovasc Surg 33(Suppl 1):S1–S75

    Article  PubMed  Google Scholar 

  6. Katsanos K, Spiliopoulos S, Krokidis M, Karnabatidis D, Siablis D (2012) Does below-the-knee placement of drug-eluting stents improve clinical outcomes? Cardiovasc Surg (Torino) 53(2):195–203

    CAS  Google Scholar 

  7. Siablis D, Karnabatidis D, Katsanos K et al (2009) Infrapopliteal application of sirolimus-eluting versus bare metal stents for critical limb ischemia: Analysis of long-term angiographic and clinical outcome. J Vasc Interv Radiol 20(9):1141–1150

    Article  PubMed  Google Scholar 

  8. Malyar N, Fürstenberg T, Wellmann J et al (2013) Recent trends in morbidity and in-hospital outcomes of in-patients with peripheral arterial disease: a nationwide population-based analysis. Eur Heart J 34(34):2706–2714

    Article  PubMed  Google Scholar 

  9. Smith SJ, Allen J, Blair S, Bonow R, Brass L, Fonarow G et al (2006) AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: Endorsed by the National Heart, Lung, and Blood Institute. Circulation 113:2363–2372

    Article  PubMed  Google Scholar 

  10. Tepe G, Bantleon R, Brechtel K et al (2012) Management of peripheral arterial interventions with mono or dual antiplatelet therapy—the MIRROR study: a randomised and double-blinded clinical trial. Eur Radiol 22(9):1998–2006

    Article  PubMed  Google Scholar 

  11. Spiliopoulos S, Pastromas G, Katsanos K, Kitrou P, Karnabatidis D, Siablis D (2013) Platelet responsiveness to clopidogrel treatment after Peripheral endovascular procedures—The PRECLOP study: clinical impact and optimal cut-off value of high on treatment platelet reactivity. J Am Coll Cardiol 61(24):2428–2434

    Article  CAS  PubMed  Google Scholar 

  12. Hamm CW, Bassand JP, Agewall S et al (2011) ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The task force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 32(23):2999–3054

    Article  PubMed  Google Scholar 

  13. Cannon CP, Harrington RA, James S, PLATelet inhibition and patient Outcomes investigators et al (2010) Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): A randomised double-blind study. Lancet 375(9711):283–293

    Article  CAS  PubMed  Google Scholar 

  14. Montalescot G, Wiviott SD, Braunwald E, TRITON-TIMI 38 investigators et al (2009) Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): Double-blind, randomised controlled trial. Lancet 28 373(9665):723–731

    Article  CAS  Google Scholar 

  15. The GUSTO investigators (1993) An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 329:673–682

    Article  Google Scholar 

  16. Cannon CP, Husted S, Harrington RA et al (2007) Safety, tolerability, and initial efficacy of AZD6140, the first reversible oral adenosine diphosphate receptor antagonist, compared with clopidogrel, in patients with non-ST-segment elevation acute coronary syndrome: Primary results of the DISPERSE-2 trial. J Am Coll Cardiol 50:1844–1851

    Article  CAS  PubMed  Google Scholar 

  17. Sacks D, Marinelli DL, Martin LG et al (2003) Reporting standards for clinical evaluation of new peripheral arterial revascularization devices. J Vasc Interv Radiol 14(9 Pt 2):S395–S404

    Article  PubMed  Google Scholar 

  18. Matetzky S, Shenkman B, Guetta V et al (2004) Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation 109:3171–3175

    Article  CAS  PubMed  Google Scholar 

  19. Gurbel PA, Bliden KP, Guyer K, Cho PW, Zaman KA, Kreutz RP et al (2005) Platelet reactivity in patients and recurrent events post-stenting results of the prepare post-stenting study. J Am Coll Cardiol 46:1820–1826

    Article  CAS  PubMed  Google Scholar 

  20. Bonello L, Tantry US, Marcucci R, for the Working Group on High On-Treatment Platelet Reactivity et al (2010) Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol 56:919–933

    Article  CAS  PubMed  Google Scholar 

  21. Spiliopoulos S, Kassimis G, Hatzidakis A, Krokidis M (2013) High on-treatment platelet reactivity in peripheral endovascular procedures. Cardiovasc Intervent Radiol. doi:10.1007/s00270-013-0707-y

    Google Scholar 

  22. Pastromas G, Spiliopoulos S, Katsanos K, Diamantopoulos A, Kitrou P, Karnabatidis D et al (2013) Clopidogrel responsiveness in patients undergoing peripheral angioplasty. Cardiovasc Intervent Radiol 36(6):1493–1499

    Article  PubMed  Google Scholar 

  23. Karnabatidis D, Spiliopoulos S, Pastromas G, Kitrou P, Christeas N, Katsanos K et al (2013) Prevalence of non responsiveness to aspirin in patients with symptomatic peripheral arterial disease using true point of care testing. Cardiovasc Intervent Radiol. doi:10.1007/s00270-013-0710-3

    Google Scholar 

  24. Ramaraj R, Movahed MR, Hashemzadeh M (2011) Novel antiplatelet agent ticagrelor in the management of acute coronary syndrome. J Interv Cardiol 24(3):199–207

    Article  PubMed  Google Scholar 

  25. Abergel E, Nikolsky E (2010) Ticagrelor: an investigational oral antiplatelet treatment for reduction of major adverse cardiac events in patients with acute coronary syndrome. Vasc Health Risk Manag 6:963–977

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Aradi D, Storey RF, Komócsi A et al (2013) Expert position paper on the role of platelet function testing in patients undergoing percutaneous coronary intervention. Eur Heart J 35(4):209–215

    Article  PubMed Central  PubMed  Google Scholar 

  27. Price MJ, Angiolillo DJ, Teirstein PS, Lillie E, Manoukian SV, Berger PB et al (2011) Platelet reactivity and cardiovascular outcomes after percutaneous coronary intervention: A time dependent analysis of the Gauging Responsiveness with a VerifyNow P2Y12 assay: impact on thrombosis and safety (GRAVITAS) trial. Circulation 124:1132–1137

    Article  PubMed  Google Scholar 

  28. Collet JP, Cuisset T, Rangé G, ARCTIC Investigators et al (2012) Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med 367(22):2100–2109

    Article  CAS  PubMed  Google Scholar 

  29. Spiliopoulos S, Katsanos K, Karnabatidis D et al (2010) Cryoplasty versus conventional balloon angioplasty of the femoropopliteal artery in diabetic patients: long-term results from a prospective randomized single-center controlled trial. Cardiovasc Intervent Radiol 33(5):929–938

    Article  PubMed  Google Scholar 

  30. Dahlen JR, Price MJ, Parise H, Gurbel PA (2013) Evaluating the clinical usefulness of platelet function testing: considerations for the proper application and interpretation of performance measures. Thromb Haemost 109(5):801–808

    Google Scholar 

  31. Stone GW, Witzenbichler B, Weisz G, ADAPT-DES Investigators et al (2013) Platelet reactivity and clinical outcomes after coronary artery implantation of drug-eluting stents (ADAPT-DES): A prospective multicentre registry study. Lancet 382(9892):614–623

    Article  PubMed  Google Scholar 

  32. Schofield CJ, Libby G, Brennan GM, MacAlpine RR, Morris AD, Leese GP (2006) Mortality and hospitalization in patients after amputation: a comparison between patients with and without diabetes. Diabetes Care 29(10):2252–2256

    Article  PubMed  Google Scholar 

  33. Alexopoulos D, Galati A, Xanthopoulou I et al (2012) Ticagrelor versus prasugrel in acute coronary syndrome patients with high on-clopidogrel platelet reactivity following percutaneous coronary intervention: A pharmacodynamic study. J Am Coll Cardiol 17 60(3):193–199

    Article  CAS  Google Scholar 

  34. Storey RF, Husted S, Harrington RA et al (2007) Inhibition of platelet aggregation by AZD6140, a reversible oral P2Y12 receptor antagonist compared with clopidogrel in patients with acute coronary syndromes. J Am Coll Cardiol 50:1852–1856

    Article  CAS  PubMed  Google Scholar 

  35. Gurbel PA, Bliden KP, Butler K et al (2009) Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: The ONSET/OFFSET study. Circulation 120:2577–2585

    Article  CAS  PubMed  Google Scholar 

  36. Storey RF, Angiolillo DJ, Patil SB et al (2010) Inhibitory effects of ticagrelor compared with clopidogrel on platelet function in patients with acute coronary syndromes: The PLATO (PLATelet inhibition and patient outcomes) PLATELET substudy. J Am Coll Cardiol 56:1456–1462

    Article  CAS  PubMed  Google Scholar 

  37. Wiviott SD, Braunwald E, McCabe CH, TRITON-TIMI 38 Investigators et al (2007) Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 357:2001–2015

    Article  CAS  PubMed  Google Scholar 

  38. Wallentin L, Becker RC, Budaj A, PLATO Investigators et al (2009) Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 361:1045–1057

    Article  CAS  PubMed  Google Scholar 

  39. Gurbel PA, Bliden KP, Butler K et al (2010) Response to ticagrelor in clopidogrel nonresponders and responders and effect of switching therapies: The RESPOND study. Circulation 121(10):1188–1199

    Article  CAS  PubMed  Google Scholar 

  40. Coleman CI, Limone BL (2013) Universal versus platelet reactivity assay-driven use of P2Y12 inhibitors in acute coronary syndrome patients. Cost-effectiveness analyses for six European perspectives. Thromb Haemost 111(1):103–110

    Article  PubMed  Google Scholar 

  41. Nawarskas JJ, Clark SM (2011) Ticagrelor: a novel reversible oral antiplatelet agent. Cardiol Rev 19(2):95–100

    Article  PubMed  Google Scholar 

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The authors have no conflict of interest.

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Authors and Affiliations

  1. Department of Interventional Radiology, School of Medicine, Patras University Hospital, Rio, 26504, Greece

    Stavros Spiliopoulos, Georgios Pastromas, Panagiotis Kitrou, Dimitris Siablis & Dimitris Karnabatidis

  2. Department of Interventional Radiology, Guy’s and St Thomas’ Hospitals, King’s Health Partners, NHS Foundation Trust, London, SE1 7EH, UK

    Konstantinos Katsanos & Athanasios Diamantopoulos

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  1. Stavros Spiliopoulos
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  2. Konstantinos Katsanos
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  3. Georgios Pastromas
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  7. Dimitris Karnabatidis
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Correspondence to Stavros Spiliopoulos.

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Spiliopoulos, S., Katsanos, K., Pastromas, G. et al. Initial Experience With Ticagrelor in Patients With Critical Limb Ischemia and High On-Clopidogrel Platelet Reactivity Undergoing Complex Peripheral Endovascular Procedures. Cardiovasc Intervent Radiol 37, 1450–1457 (2014). https://doi.org/10.1007/s00270-014-0852-y

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