Bivalirudin versus heparin and glycoprotein IIb/IIIa inhibition among patients with renal impairment undergoing percutaneous coronary intervention (a subanalysis of the REPLACE-2 trial).
Among patients who undergo percutaneous coronary intervention, renal impairment is associated with an excessive risk of bleeding and ischemic events. Bivalirudin provides comparable suppression of ischemic events with a decrease in bleeding events compared with heparin and glycoprotein IIb/IIIa inhibition. We examined the relation between adverse events, renal impairment, and antithrombotic therapy within a randomized comparison. The Second Randomized Evaluation in PCI Linking Bivalirudin to Reduced Clinical Events per-protocol study population was assessed. Renal function was defined as calculated creatinine clearance <60 ml/min. Events within the overall study population and within each study arm were assessed. Thirty-day events by renal function were compared by chi-square test and logistic regression. Late mortality was compared by log-rank test. Interaction analyses were performed. Among 5,710 patients, renal impairment was associated with increased ischemic events (hazard ratio 1.45, 95% confidence interval 1.13 to 1.88, p = 0.004), bleeding complications (hazard ratio 1.72, 95% confidence interval 1.06 to 2.80, p = 0.028), and excessive 12-month mortality (hazard ratio 3.85, 95% confidence interval 2.67 to 5.54, p <0.001). Bivalirudin provided suppression of ischemic events that was comparable to heparin and glycoprotein IIb/IIIa inhibition regardless of renal impairment. Fewer bleeding events with bivalirudin were also evident irrespective of renal dysfunction. No interaction between treatment assignment, bleeding or ischemic complications, and renal impairment was observed. The safety and efficacy of bivalirudin compared with heparin and planned glycoprotein IIb/IIIa inhibition in this high-risk group are comparable and consistent with the results of the overall trial.
Chew
Derek P
DP
Department of Cardiovascular Medicine, Flinders Medical Centre, Bedford Park, South Australia, Australia. derek.chew@flinders.edu.au
Lincoff
A Michael
AM
Gurm
Hitinder
H
Wolski
Katherine
K
Cohen
David J
DJ
Henry
Tim
T
Feit
Frederick
F
Topol
Eric J
EJ
D000077284:Abciximab; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000925:Anticoagulants / Q000627:therapeutic use*; D017225:Atherectomy, Coronary / Q000009:adverse effects; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000077542:Eptifibatide; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006470:Hemorrhage / Q000517:prevention & control; D006493:Heparin / Q000627:therapeutic use*; D006629:Hirudins / Q000031:analogs & derivatives*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; D007431:Intraoperative Complications / Q000517:prevention & control; D007511:Ischemia / Q000517:prevention & control; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000627:therapeutic use*; D010455:Peptides / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000627:therapeutic use*; D051437:Renal Insufficiency / Q000150:complications*; D015607:Stents; D016019:Survival Analysis; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D005343:Fibrinolytic Agents; D006629:Hirudins; D007140:Immunoglobulin Fab Fragments; D010446:Peptide Fragments; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; D006493:Heparin; D000077542:Eptifibatide; C074619:bivalirudin; D000077284:Abciximab