Bivalirudin Versus Heparin in Percutaneous Coronary Intervention-a Systematic Review and Meta-analysis of Randomized Trials Stratified by Adjunctive Glycoprotein IIb/IIIa Strategy

Overview

Journal J Thorac Dis

Publisher AME Publishing Company

Specialty Pulmonary Medicine

Date 2018 Aug 3

PMID 30069330

Citations 7

Authors

Mahesh Anantha-Narayanan

Dixitha Anugula

Nagarjuna R Gujjula

Yogesh N V Reddy

Janani Baskaran

Manu Kaushik

Venkata M Alla

Ganesh Raveendran

Affiliations

Soon will be listed here.

Abstract

Background: Bivalirudin has been shown to be associated with less major bleeding than heparin in patients undergoing percutaneous coronary intervention (PCI); but the confounding effect of concomitant glycoprotein IIb/IIIa inhibitors (GPI) limits meaningful comparison. We performed a systematic review and meta-analysis to compare bivalirudin to heparin, with and without adjunctive GPI in PCI.

Methods: We searched PubMed, Cochrane, EMBASE, CINAHL and WOS from January 2000 to December 2017 for clinical trials comparing bivalirudin to heparin, with and without adjunctive GPI during PCI. Cochrane's Q statistics were used to determine heterogeneity. Random effects model was used.

Results: Twenty-six comparison groups (22 original studies and 4 subgroup analyses) with 53,364 patients were included. Mean follow-up was 192±303 days. There was no difference between the two groups in all-cause mortality [risk ratio (RR: 0.93; 95% CI: 0.82-1.05, P=0.260), target vessel revascularization (TVR) (RR: 1.17; 95% CI: 0.93-1.46, P=0.174) or stroke (RR: 0.91; 95% CI: 0.71-1.18, P=0.490). Major bleeding was lower in the bivalirudin group with concomitant GPI in one or both arms (RR: 0.64; 95% CI: 0.53-0.77, P<0.001) and without (RR: 0.71; 95% CI: 0.51-0.99, P=0.041) provisional or routine GPIs. Bivalirudin appeared to have a higher risk of stent thrombosis (RR: 1.32; 95% CI: 1.04-1.68, P=0.022) and a trend towards more myocardial infarction (RR: 1.12; 95% CI: 0.98-1.28, P=0.098) though without statistical significance. However, exclusion of studies with GPI showed no difference in stent thrombosis or myocardial infarction with bivalirudin.

Conclusions: Bivalirudin is associated with less major bleeding compared to heparin, regardless of GPI use. The lower anticoagulant effect of bivalirudin is linked with higher stent thrombosis and a trend towards more MI, however a confounding effect of GPI use in the heparin arm cannot be excluded.

Citing Articles

Bivalirudin versus heparin in contemporary percutaneous coronary interventions for patients with acute coronary syndrome: a systematic review and meta-analysis.

Zhang J, Chen Z, Wang D, Li C, Luo F, He Y Cardiol J. 2023; 31(2):309-320.

PMID: 37964648 PMC: 11076038. DOI: 10.5603/cj.90956.

Superiority of bivalirudin over heparin anticoagulation therapy for extracorporeal membrane oxygenation? Too early to draw conclusions.

Gu J, Yu H, Lin D Heliyon. 2023; 9(2):e13530.

PMID: 36865472 PMC: 9970897. DOI: 10.1016/j.heliyon.2023.e13530.

A meta-analysis and cost-minimization analysis of bivalirudin versus heparin in high-risk patients for percutaneous coronary intervention.

Sun K, Cui B, Cao S, Wang W, Yu F, Wang J Pharmacol Res Perspect. 2021; 9(3):e00774.

PMID: 33939886 PMC: 8092421. DOI: 10.1002/prp2.774.

Anticoagulants Used in Cardiac Catheterization of Patients With Chronic Lymphocytic Leukemia: A Case Report and Overview.

Mararenko A, Alshami A, AlAzzawi M, Patel S Cureus. 2021; 13(3):e13633.

PMID: 33816032 PMC: 8011627. DOI: 10.7759/cureus.13633.

Triglyceride to high-density lipoprotein cholesterol ratio as a risk factor of repeat revascularization among patients with acute coronary syndrome after first-time percutaneous coronary intervention.

Su Y, Zhang R, Xu R, Wang H, Geng H, Pan M J Thorac Dis. 2020; 11(12):5087-5095.

PMID: 32030225 PMC: 6988028. DOI: 10.21037/jtd.2019.12.26.

References

Webster M, Stables R . Bivalirudin versus Heparin Monotherapy in Myocardial Infarction. N Engl J Med. 2018; 378(3):299. DOI: 10.1056/NEJMc1714520. View

Borenstein M, Hedges L, Higgins J, Rothstein H . A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods. 2015; 1(2):97-111. DOI: 10.1002/jrsm.12. View

Han Y, Guo J, Zheng Y, Zang H, Su X, Wang Y . Bivalirudin vs heparin with or without tirofiban during primary percutaneous coronary intervention in acute myocardial infarction: the BRIGHT randomized clinical trial. JAMA. 2015; 313(13):1336-46. DOI: 10.1001/jama.2015.2323. View

Zeymer U, van t Hof A, Adgey J, Nibbe L, Clemmensen P, Cavallini C . Bivalirudin is superior to heparins alone with bailout GP IIb/IIIa inhibitors in patients with ST-segment elevation myocardial infarction transported emergently for primary percutaneous coronary intervention: a pre-specified analysis from the.... Eur Heart J. 2014; 35(36):2460-7. PMC: 4169872. DOI: 10.1093/eurheartj/ehu214. View

. Randomised placebo-controlled and balloon-angioplasty-controlled trial to assess safety of coronary stenting with use of platelet glycoprotein-IIb/IIIa blockade. Lancet. 1998; 352(9122):87-92. DOI: 10.1016/s0140-6736(98)06113-3. View

Moscucci M, Fox K, Cannon C, Klein W, Lopez-Sendon J, Montalescot G . Predictors of major bleeding in acute coronary syndromes: the Global Registry of Acute Coronary Events (GRACE). Eur Heart J. 2003; 24(20):1815-23. DOI: 10.1016/s0195-668x(03)00485-8. View

Lincoff A, Bittl J, Kleiman N, Sarembock I, Jackman J, Mehta S . 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(9):1092-6. DOI: 10.1016/j.amjcard.2004.01.033. View

Patti G, Pasceri V, DAntonio L, DAmbrosio A, Macri M, Dicuonzo G . Comparison of safety and efficacy of bivalirudin versus unfractionated heparin in high-risk patients undergoing percutaneous coronary intervention (from the Anti-Thrombotic Strategy for Reduction of Myocardial Damage During Angioplasty-Bivalirudin.... Am J Cardiol. 2012; 110(4):478-84. DOI: 10.1016/j.amjcard.2012.04.017. View

. Novel dosing regimen of eptifibatide in planned coronary stent implantation (ESPRIT): a randomised, placebo-controlled trial. Lancet. 2001; 356(9247):2037-44. DOI: 10.1016/S0140-6736(00)03400-0. View

10.

Stone G, Witzenbichler B, Guagliumi G, Peruga J, Brodie B, Dudek D . Heparin plus a glycoprotein IIb/IIIa inhibitor versus bivalirudin monotherapy and paclitaxel-eluting stents versus bare-metal stents in acute myocardial infarction (HORIZONS-AMI): final 3-year results from a multicentre, randomised controlled trial. Lancet. 2011; 377(9784):2193-204. DOI: 10.1016/S0140-6736(11)60764-2. View

11.

Stone G, White H, Ohman E, Bertrand M, Lincoff A, McLaurin B . 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(9565):907-19. DOI: 10.1016/S0140-6736(07)60450-4. View

12.

Schulz S, Kastrati A, Ferenc M, Massberg S, Birkmeier K, Laugwitz K . One-year outcomes with abciximab and unfractionated heparin versus bivalirudin during percutaneous coronary interventions in patients with non-ST-segment elevation myocardial infarction: updated results from the ISAR-REACT 4 trial. EuroIntervention. 2013; 9(4):430-6. DOI: 10.4244/EIJV9I4A71. View

13.

Xiang D, Gu X, Song Y, Huang W, Tang L, Yin Y . Evaluation on the efficacy and safety of domestic bivalirudin during percutaneous coronary intervention. Chin Med J (Engl). 2013; 126(16):3064-8. View

14.

Shahzad A, Kemp I, Mars C, Wilson K, Roome C, Cooper R . Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomised controlled trial. Lancet. 2014; 384(9957):1849-1858. DOI: 10.1016/S0140-6736(14)60924-7. View

15.

Gladwell T . Bivalirudin: a direct thrombin inhibitor. Clin Ther. 2002; 24(1):38-58. DOI: 10.1016/s0149-2918(02)85004-4. View

16.

Cavender M, Sabatine M . Bivalirudin versus heparin in patients planned for percutaneous coronary intervention: a meta-analysis of randomised controlled trials. Lancet. 2014; 384(9943):599-606. DOI: 10.1016/S0140-6736(14)61216-2. View

17.

Romagnoli E, Biondi-Zoccai G, Sciahbasi A, Politi L, Rigattieri S, Pendenza G . Radial versus femoral randomized investigation in ST-segment elevation acute coronary syndrome: the RIFLE-STEACS (Radial Versus Femoral Randomized Investigation in ST-Elevation Acute Coronary Syndrome) study. J Am Coll Cardiol. 2012; 60(24):2481-9. DOI: 10.1016/j.jacc.2012.06.017. View

18.

Feldman A, Suleiman K, Bushari L, Yahalom M, Rozner E, Freedberg N . Bivalirudin versus Unfractionated Heparin during Percutaneous Coronary Intervention in Patients at High Risk for Bleeding. Int J Angiol. 2014; 23(4):227-32. PMC: 4244240. DOI: 10.1055/s-0034-1372244. View

19.

Schulz S, Mehilli J, Ndrepepa G, Neumann F, Birkmeier K, Kufner S . Bivalirudin vs. unfractionated heparin during percutaneous coronary interventions in patients with stable and unstable angina pectoris: 1-year results of the ISAR-REACT 3 trial. Eur Heart J. 2010; 31(5):582-7. DOI: 10.1093/eurheartj/ehq008. View

20.

Erlinge D, Omerovic E, Frobert O, Linder R, Danielewicz M, Hamid M . Bivalirudin versus Heparin Monotherapy in Myocardial Infarction. N Engl J Med. 2017; 377(12):1132-1142. DOI: 10.1056/NEJMoa1706443. View