Objective: To determine and compare the incidence of in-hospital and 30-day hemorrhagic complications and major adverse cardiac events (MACEs) as evidence of safety and efficacy using Bivalirudin versus Heparin in diabetic acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) in a tertiary care cardiac hospital.
Background: Prevention of hemorrhagic complications has emerged as a priority in patients undergoing PCI in addition to suppressing thrombotic complications. This goal is challenging to achieve in diabetic ACS patients as DM itself is a prothrombotic state with more pronounced vascular injury response and have a worse outcome after PCI compared with non-diabetic patients. In patients with ACS, Bivalirudin has been shown to result in similar rates of composite ischemia as Heparin plus GPI (GP IIb /IIIa inhibitor), while significantly reducing major bleeding and has received class I recommendation for PCI. Whether Bivalirudin is safe and effective in diabetic ACS patients undergoing PCI, as compared with Heparin (UFH) monotherapy, is unknown.
Methods: 218 diabetic ACS patients (age>18 years and ≤ 75 years) who underwent PCI from May 2018 to April 2019 at UCC, BSMMU, Dhaka, Bangladesh were randomly assigned to have UFH or Bivalirudin. Before the guide wire crossed the lesion, 111 patients in the UFH group received a bolus of 70-100 U/kg (targeted activated clotting time, ACT: 200-250 s). 107 patients in the Bivalirudin group received a loading dose of 0.75 mg/kg, followed by an infusion of 1.75 mg/kg/h for up to 4 hours. Dual antiplatelet (DAPT) loading as Aspirin 300 mg plus P2Y12 inhibitors (Clopidogrel 600 mg or Prasugrel 60 mg or Ticagrelor 180 mg) was given in all patients before the procedure. The maintenance dose of DAPT was continued for at least one month and patients were followed telephonically up to 30 days. The outcome measures were in-hospital and 30-day hemorrhagic complications and MACEs [death, MI, target vessel revascularization (TVR) and stroke].
Results: Patients treated with Bivalirudin compared with Heparin had a significantly lower in-hospital incidence of QMI (0% vs. 6%; p=0.03) and major bleeding (0% vs. 7%; p=0.02). However, the incidence of cardiac death, stent thrombosis, TVR were no differences between the groups (p>0.05). There was only one NQMI in the Bivalirudin group as opposed to 8% in the Heparin group in 30 days following stenting (p=0.04). No other adverse effects were found significantly different between groups in 30 days of PCI.
Conclusion: In this small scale, prospective, randomized controlled study of diabetic ACS patients undergoing PCI in a single center showed that Bivalirudin is safe and effective as it reduces immediate and short-term hemorrhagic complications as well as MACEs as compared with Heparin.
Cader, F.A., Haq, M.M., Nasrin, S. & Kabir, C.M. 2017, Presentation, Management Practices and In-hospital Outcomes of Patients with Acute Coronary Syndrome in a tertiary Cardiac Centre in Bangladesh' Bangladesh Heart Journal, vol.32, no.2, pp.106-13.
Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet 1997; 349(9064):1498-504.
Islam, A. & Majumder, A. 2013, Coronary Artery Disease in Bangladesh, Indian Heart Journal, vol. 65, no.4, pp. 424-35.
Libby P. Mechanisms of acute coronary syndromes and their implications for therapy. N Engl J Med. 2013; 368 (21):2004–13.
Bagai A, Dangas GD, Stone GW, Granger CB. Reperfusion strategies in acute coronary syndromes. Circ Res. 2014; 114(12):1918-28.
Lincoff, A.M., Bittl, J.A. & Harrington, R.A. 2003, Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during the percutaneous coronary intervention: REPLACE-2 randomized trial' Journal of American Medical Association, vol.289, no.7, pp.853-63.
Sohrabuzzaman APM, Zaman F, Mohammad N. 2017, Effect of Bivalirudin and Abciximab on myocardial necrosis in PCI patients, Bangladesh J Cardiol, 2017; 07 (01-02): 707-11
Zhang, J. & Yang, X. 2017, Efficacy and Safety of bivalirudin versus heparin in patients with diabetes mellitus undergoing percutaneous coronary intervention, Medicine (Baltimore) journal, vol. 96, no.29, pp. e7204.
Gurm, H., Sarembock, I., Kereiakes, D., Young, J., Harrington, R., Kleiman, N.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 'Journal of the American College of Cardiology, vol. 45, no.12, pp. 1932-38.
Kastrati, A., Neumann, F.J. & Schulz, S., 2011, Abciximab and heparin versus bivalirudin for non-ST-elevation myocardial infarction, New England Journal of Medicine, vol. 365, no.21, pp. 1980-89.
Hirsh J, van Aken WG, Gallus AS, et al. Heparin kinetics in venous thrombosis and pulmonary embolism. Circulation.1976;53(4):691-695.
Young E, Prins M, Levine MN, Hirsh J. Heparin binding to plasma proteins, an important mechanism for heparin resistance. Thromb Haemost. 1992;67(6):639-643.
Barzu T, Molho P, Tobelem G, et al. Binding and endocytosis of heparin by human endothelial cells in culture. Biochim Biophys Acta. 1985; 845 (2):196-203.
Sobel M, McNeill PM, Carlson PL, et al. Heparin inhibition of von Willebrand factor-dependent platelet function in vitro and in vivo. J Clin Invest. 1991; 87(5):1787-1793.
Hirsh J, Guyatt G, Albers GW, et al; American College of Chest Physician. Antithrombotic and thrombolytic therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008; 133(6 Suppl) :110S-112S.
Lincoff, A.M., Califf, R.M. & Topol, E.J. 2000, Platelet glycoprotein IIb/IIIa blockade in coronary artery disease', Journal of the American College of Cardiology, vol.35, no.5, pp.1103-115.
Stone, G.W., White, H.D. & Ohman, E.M. 2007, Bivalirudin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a subgroup analysis from the Acute Catheterization and Urgent Intervention Triage strategy (ACUITY) trial, The Lancet, vol. 369, no.9565, pp. 907-19.
Stone, G.W., Witzenbichler, B. & Guagliumi, G. 2008, Bivalirudin during primary PCI in acute myocardial infarction, New England Journal of Medicine, vol. 358, no.21, pp 2218-30.
Han, Y., Guo, J. & Zheng, Y.2015, Bivalirudin vs. heparin with or without tirofiban during primary percutaneous coronary intervention in acute myocardial infarction: the BRIGHT randomized clinical trial, Journal of American Medical Association, vol.313, no.13, pp.1336-46.
Nairooz, R., Sardar, P. & Amin, H., 2015. Short- and long-term outcomes in diabetes patients undergoing percutaneous coronary intervention with bivalirudin compared with heparin and glycoprotein IIb/IIIA inhibitors: a meta-analysis of randomized trials, Catheterization and Cardiovascular Intervention, vol.86, no.3, pp.364–75.
O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;61: e78.
Roffi M, Patrono C, Collet JP, et al. 2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016;37(3):267-315.
Shahzad, A., Kemp, I. & Mars, C.2014, Unfractionated heparin versus bivalirudin inprimary percutaneous coronary intervention (HEAT-PPCI): an open-label, single-center, randomized controlled trial' Lancet, Vol.384, no.9957, pp.1849-58.
Leonardi, S., Frigoli, E. & Rothenbuhler, M. 2016, Bivalirudin or unfractionated heparin in patients with acute coronary syndromes managed invasively with and without ST elevation (MATRIX): randomized controlled trial, British Medical Journal, vol. 354, pp. i4935.
Thygesen K, Alpert JS, White HD, et al. for the Joint ESC/ACC/ AHA/WHF Task Force for the Redefinition of Myocardial Infarction. Universal definition of myocardial infarction. Circulation. 2007; 116: 2634e2653.
Laskey WK, Yancy CW, Maisel WH. Thrombosis in coronary drug-eluting stents: a report from the meeting of the Circulatory System Medical Devices Advisory Panel of the Food and Drug Administration Center for Devices and Radiologic Health, December 7e8, 2006. Circulation. 2007; 115:2352e2357.
Kaul, U., Dua, A. & Sethi, A. K. 2015, Comparison of anti-thrombotic strategies using bivalirudin, Heparin plus Glycoprotein IIb/IIIa inhibitors, and Unfractionated Heparin Monotherapy for patients undergoing percutaneous coronary intervention—A single canter observational study' Indian Heart Journal, vol.67, no.4, pp. 311-17.
Feit, F., Manoukian, S.V. & Ebrahimi, R. 2008, Safety and Efficacy of Bivalirudin Monotherapy in Patients with Diabetes Mellitus and Acute Coronary Syndromes', Journal of the American College of Cardiology, vol.51, no. 17, pp.1645-52.
Witzenbichler, B., Mehran, R., Guagliumi, G., Dudek, D., Huber, K., Kornowski, R.2011, Impact of diabetes mellitus on the safety and effectiveness of bivalirudin in patients with acute myocardial infarction undergoing primary angioplasty: analysis from the HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction), JACC: Cardiovascular Interventions, vol. 4, no.7, pp. 760-68.
Steg PG, van't Hof A, Clemmensen P, et al. Design and methods of European Ambulance Acute Coronary Syndrome Angiography Trial (EURO MAX): an international randomized open-label ambulance trial of bivalirudin versus standard-of-care anticoagulation in patients with acute ST-segment elevation myocardial infarction transferred for primary percutaneous coronary intervention. Am Heart J. 2013 Dec; 166:960e967.
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