Clinical Outcome of Patients of Acute Coronary Syndrome at 7 and 30 days Undergoing Percutaneous Coronary Interventions and Treated with Bivalirudin and Heparin

  • Kumar A Cadila Pharmaceuticals Ltd, Ahmedabad, Gujarat, India
  • Kachhadiya R Department of Pharmacology, Faculty of Pharmacy, NIRMA University, Ahmedabad, Gujarat India.
  • Chakraborty BS
Keywords: Major bleeding, Net clinical outcomes, MACE, Bivalirudin, Heparin

Abstract

Background:Recent data suggest that Bivalirudin provides ischemic protection superior to Heparin,and comparable to Heparin plus glycoprotein IIb/IIIa inhibitors, with significantly fewer bleeding complications. Whetherthis advantage persists in large population has not beenfully defined. Objective: This study systematically evaluates clinical outcomes of treatment with Bivalirudinvs Heparin in patients of acute coronary syndrome undergoing Percutaneous coronary interventions (PCI). Methods: We analyzed prospective, randomized controlled trials via electronic searches that have reported clinical outcomes at 7 and 30 days. The outcomes were major bleeding, net clinical outcomes and Major Adverse Cardiac Events – MACE. Data from individual trials were combined by a meta analysis method of Mantel-Haenszelcalculate a relative risk (RR) and 95% confidence interval (95%CI) across the studies.Theheterogeneity across the trials was assessed through χ2 statistic, I2 andvisual inspection of the forest plots. Results: This meta-analysis involved a total of 30,088 patients (Bivalirudin, n=15,105; Heparin, n=14,983). Compared with Heparin, Bivalirudin was associated with a lower risk of major bleeding (RR 0.38; 95%CI 0.29-0.48 at 7 days and RR 0.67;95%CI 0.60-0.75 at 30 days), net clinical outcomes (RR 0.56; 95%CI 0.47-0.66 at 7 days and RR 0.89; 95%CI 0.83- 0.96 at 30 days) and MACE (RR 0.78; 95%CI 0.63-0.96 at 7 days). There was no significant difference in case of MACE at 30 days (RR 1.02; 95%CI 0.93-1.11). Heterogeneity was observed across the trials that reported major bleeding (χ2=14.71, 5 df, p=0.01, I2=66%) at 30 days, but not at 7 days for reported major bleeding, and also for net clinical outcomes and MACE both at 7 days and 30 days. Conclusion: This analysis further supports that Bivalirudin provides significantimprovement in net clinical outcomes and MACE with a significant reduction of bleedingcomplications.

References

1. Stone GW, White HD, Ohman EM. 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. Lancet 2007;369:907-919.
2. Stone GW, Witzenbichler B, Guagliumi G. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J
Med 2008;358:2218-2230
3. Kastrati A, Neumann FJ, Mehilli J, Byrne RA, Iijima R, Büttner HJ, et al. Bivalirudin versus Unfractionated Heparin
during Percutaneous Coronary Intervention. N Engl J Med 2008;359:688-96.
26 Published 30 March 2016
DOI: 10.1234.67/jmpr.1014
JMPR 2016, 2, 21-26
4. Lincoff AM, Bittl JA, Kleiman NS. 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 2004;93:1092-1096.
5. Lincoff AM, Bittl JA, Harrington RA. Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with
Heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: REPLACE-2 randomized
trial. JAMA 2003;289:853-63.
6. Bittl JA, Chaitman BR, Feit F, Kimball W, Topol EJ. Bivalirudin versus Heparin during coronary angioplasty for
unstable or postinfarction angina: final report reanalysis of the Bivalirudin Angioplasty Study (BAT). Am Heart J
2001;142:952-959
7. Lincoff AM, Kleiman NS, Kottke-Marchant K. Bivalirudin with planned or provisional abciximab versus low-dose
Heparin and abciximab during percutaneous coronary revascularization: results of the Comparison of Abciximab
Complications with Hirulog for Ischemic Events Trial (CACHET). Am Heart J 2002;143:847-853
8. Bertrand ME, Simoons ML, Fox KA. Management of acute coronary syndromes in patients presenting without persistent
ST-segment elevation. Eur Heart J 2002;23:1809-40.
9. Xavier D, Pais P, Devereaux P. Treatment and outcomes of acute coronary syndromes in India (CREATE): a prospective
analysis of registry data The Lancet 2008;371:1435-1442.
10. Gruentzig AR. Percutaneous transluminal coronary angioplasty. SeminRoentgenol 1981;16:152–153.
11. Graves EJ, Kozak LJ. Detailed diagnosis and procedures, National Hospital Discharge Survey, 1996. No. 138. Hyattsville,
MD: National Center for Health Statistics, 1998. (DHHS publication no. 98-1799.)
12. Braunwald E, Antman EM, Beasley JW. Management of patients with unstable angina and non-ST segment elevation
myocardial infarction: a report of the American College of Cardiology/American Heart Association Task
Force on Practice Guidelines [Serial on the Internet]. [cited 2009 May 15]. Available from:
http://www.acc.org/qualityandscience/clinical/guidelines/unstable/unstable_pkt.pdf
13. Braunwald E, Antman EM, Beasley JW. ACC/AHA guideline update for the management of patients with unstable
angina and non-ST-segment elevation myocardial infarction — 2002: summary article: a report of the American
College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management
of Patients With Unstable Angina). Circulation 2002;106:1893-900.
14.Weitz JI, Hudoba M, Massel D, Maraganore J, Hirsh J. Clot-bound thrombin is protected from inhibition by Heparin-antithrombin
III but is susceptible to inactivation by antithrombin III independent inhibitors. J Clin Invest
1990;86:385-391.
15. Eitzman DT, Chi L, Saggin L, Schwartz RS, Lucchesi BR, Fay WP. Heparin neutralization by plateletrich thrombi:
role of platelet factor 4. Circulation 1994;89:1523-1529.
16.Xiao Z, Theroux P. Platelet activation with unfractionated Heparin at therapeutic concentrations and comparisons
with a low-molecular-weight Heparin and with a direct thrombin inhibitor. Circulation 1998;97:251-256.
17. Sobel M, Fish WR, Toma N. Heparin modulates integrin function in human platelets. J VascSurg 2001;33:587-594.
18. Lincoff AM, Califf RM, Topol EJ. Platelet glycoprotein IIb/IIIa blockade in coronary artery disease. J Am CollCardiol
2000;35:1103-1115.
19. Kong DF, Topol EJ, Bittl JA. Clinical outcomes of Bivalirudin for ischemic heart disease. Circulation 1999;100;2049-
2053.
20. Stewart LA, Clarke MJ. Practical methodology of metaanalyses (overviews) using updated individual patient data.
Stat Med 1995;14:2057-2079.
21. Fuchs J, Cannon CP. Hirulog in the treatment of unstable angina. Results of the Thrombin Inhibition in Myocardial
Ischemia (TIMI) 7 trial. Circulation 1995;92:727-733.
22. Théroux P, Perez-Villa F, Waters D, Lesperance J, Shabani F, Bonan R. Randomized double-blind comparison of
two doses of Hirulog with Heparin as adjunctive therapy to streptokinase to promote early patency of the infarctrelated
artery in acute myocardial infarction. Circulation 1995;91:2132-2139.
23.White HD, Aylward PE, Frey MJ. Randomized, double-blind comparison of hirulog versus Heparin in patients
receiving streptokinase and aspirin for acute myocardial infarction (HERO). Hirulog Early Reperfusion/Occlusion
(HERO) Trial Investigators. Circulation 1997;96:2155-2161.
24. Bittl JA, Strony J, Brinker JA. Treatment with Bivalirudin (Hirulog) as compared with Heparin during coronary
angioplasty for unstable or postinfarction angina. Hirulog Angioplasty Study Investigators. N Engl J Med
1995;333:764-769.
25. Singh S, Molnar J, Arora R. Efficacy and Safety of BivalirudinVersus Heparins in Reduction of Cardiac Outcomes
in Acute Coronary Syndrome and Percutaneous Coronary Interventions. J CardiovascPharmacolTher2007; 12; 283-
293.
Published
2016-09-23
Section
Articles