bivalirudin and Kidney-Failure--Chronic

Patients with renal failure have an increased risk of both thrombotic and bleeding complications. A number of antithrombotic drugs undergo renal clearance. Therefore, estimation of renal function is necessary when prescribing these drugs to patients with renal dysfunction. Pharmacokinetic and clinical data in patients with chronic renal impairment are limited for several anticoagulants, and adequate administration information is often absent. Dose adjustment of anticoagulants may be indicated when the creatinine clearance falls below 30 mL/min. Unfractionated heparin, argatroban, and vitamin K antagonists generally do not require dose adjustment with renal dysfunction. However, smaller doses of warfarin may be required to achieve a particular target international normalized ratio. Close monitoring of anticoagulation is recommended when argatroban or high doses of unfractionated heparin are administered in patients with severe chronic renal impairment. Low-molecular weight heparins, danaparoid sodium, hirudins, and bivalirudin all undergo renal clearance. Lower doses and closer anticoagulation monitoring may be advisable when these agents are used in patients with chronic renal failure. We recommend that fondaparinux sodium and ximelagatran (not yet licensed) be avoided in the presence of severe renal impairment and be used with caution in patients with moderate renal dysfunction. While acknowledging the lack of pharmacokinetic data, this review provides specific recommendations for the use of anticoagulants in patients with chronic renal impairment.

Topics: Anticoagulants; Arginine; Azetidines; Benzylamines; Fondaparinux; Heparin; Hirudins; Humans; Kidney Failure, Chronic; Peptide Fragments; Pipecolic Acids; Polysaccharides; Recombinant Proteins; Sulfonamides; Warfarin

Chronic kidney disease is associated with an increased risk of ischemic and bleeding events after percutaneous coronary intervention (PCI). The direct thrombin inhibitor bivalirudin reduces these combined events. We sought to assess whether this benefit was influenced by renal function. A meta-analysis of 3 randomized trials (n = 5,035) comparing bivalirudin with heparin during PCI, stratified by estimated creatinine clearance using the Cockcroft-Gault equation (>90 [n = 1,578], 90 to 60 [n = 2,163], 59 to 30 [n = 1,255], and <30 ml/min [n = 39]), was conducted. The composite end points of death, myocardial infarction or revascularization, hemorrhage, and combined ischemic or bleeding events were assessed. A common odds ratio for each creatinine clearance strata was estimated with a random-effects model. The interaction between renal impairment and benefit from bivalirudin was assessed. Adverse ischemic and bleeding events increased with decreasing renal function. The relative benefit of bivalirudin with respect to ischemic and bleeding events was maintained within each stratum. The absolute benefit in terms of ischemic and bleeding complications increased with decreasing creatinine clearance (normal 2.2%, mild 5.8%, moderate 7.7%, severe 14.4%; p trend <0.001, interaction p = 0.044). Renal dysfunction remains a prevalent risk factor for ischemic and bleeding events in patients who undergo PCI. Bivalirudin provides greater absolute benefit in patients with impaired renal function.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Coronary Artery Disease; Creatinine; Female; Fibrinolytic Agents; Hirudins; Humans; Hypertension; Ischemia; Kidney Failure, Chronic; Male; Middle Aged; Peptide Fragments; Postoperative Hemorrhage; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Factors; Sex Factors

Elevation of baseline cardiac troponin in patients presenting with acute coronary syndromes (ACS) confers an adverse prognosis. The prognostic value of troponin elevation in patients with chronic kidney disease (CKD) and ACS is less certain.. In the ACUITY (Acute Catheterization and Urgent Intervention Triage strategy) trial, 13 819 patients with moderate and high-risk ACS were assigned randomly to receive heparin plus a glycoprotein IIb/IIIa inhibitor (GPI), bivalirudin plus a GPI, or bivalirudin monotherapy. Among 2179 patients with CKD (creatinine clearance <60 mL/min), baseline troponin elevation was present in 1291 patients (59.2%). Major bleeding and major adverse cardiac events (MACE), including death, myocardial infarction (MI), or unplanned revascularization, were examined according to baseline troponin status and randomization arm. Patients with CKD in whom the baseline troponin level was elevated had significantly higher rates of death, MI, and MACE at 30 days and 1 year compared with CKD patients without elevated baseline troponin. By multivariable analysis, baseline troponin elevation in patients with CKD was an independent predictor of composite death or MI at 30 days (hazard ratio [95% CI]=2.05 [1.48, 2.83], P<0.0001) and 1 year (1.72 [1.36, 2.17], P<0.0001). In CKD patients with baseline troponin elevation, bivalirudin monotherapy compared with heparin plus a GPI significantly reduced the 30-day rates of major bleeding with nonsignificantly different rates of MACE at 30 days and 1 year.. In patients with ACS and CKD, baseline troponin elevation is associated with significantly worse short- and long-term clinical outcomes. Bivalirudin monotherapy safely reduces major bleeding in ACS patients with CKD and baseline troponin elevation.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00093158.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Biomarkers; Female; Fibrinolytic Agents; Follow-Up Studies; Heparin; Hirudins; Humans; Kidney Failure, Chronic; Male; Myocardial Infarction; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Prognosis; Recombinant Proteins; Reference Standards; Survival Analysis; Troponin T

Patients with end-stage renal disease undergoing percutaneous coronary intervention (PCI) have largely been excluded from trials of antithrombotic therapies leaving little data to guide agent choice in this population.. The National Cardiovascular Data Registry CathPCI Registry was used to identify patients with end-stage renal disease undergoing PCI who received monotherapy with either bivalirudin or unfractionated heparin (UFH) (n=71 675). In hospital bleeding and mortality were compared and adjusted using the CathPCI Registry logistic regression models with generalized estimating equations with UFH as the reference. Bivalirudin was used in 51.3% of patients versus 48.7% for UFH. The use of bivalirudin decreased over time, and in 2014, UFH became the most frequently used. Patients receiving UFH were more likely to have an acute coronary syndrome presentation (37.8% versus 27.4%) or have cardiogenic shock (3.74% versus 1.98%). The observed rates for in hospital bleeding (7.0% versus 9.5%; adjusted odds ratio,0.82; 95% confidence interval, 0.76-0.87) and mortality (2.6% versus 4.2%; adjusted odds ratio, 0.87; 95% confidence interval, 0.78-0.97) were lower for patients receiving bivalirudin compared with those receiving UFH.. In patients with end-stage renal disease undergoing PCI, bivalirudin and UFH were used with similar frequency although the patterns of use changed over the enrollment period. Patients with end-stage renal disease undergoing PCI had a lower adjusted risk of in hospital outcomes with bivalirudin; however, given the observational nature of this analysis, a randomized trial is warranted.

Topics: Aged; Anticoagulants; Antithrombins; Coronary Artery Disease; Female; Hemorrhage; Heparin; Hirudins; Hospital Mortality; Humans; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Practice Patterns, Physicians'; Recombinant Proteins; Registries; Risk Factors; Time Factors; Treatment Outcome

Chronic dialysis-dependent patients undergoing percutaneous coronary intervention (PCI) are at a greater risk of bleeding and ischemic events. Bivalirudin has been associated with fewer bleeding complications than unfractionated heparin (UFH) in patients undergoing PCI in various clinical settings. These studies, however, have systematically excluded patients dependent on chronic dialysis. We sought to assess the safety, bleeding rates, and in-hospital outcomes of bivalirudin use compared to UFH use alone in patients requiring dialysis and undergoing PCI. A retrospective analysis of 396 dialysis-dependent patients undergoing PCI from January 2000 to March 2009 was performed. Patients treated with a dose-adjusted bivalirudin regimen (n = 267) were compared to those treated with UFH alone (n = 129). The primary end point of major bleeding (hematocrit decrease > or = 15%, gastrointestinal or intracerebral bleeding) and the composite end point of in-hospital death, nonfatal Q-wave myocardial infarction, and urgent target vessel revascularization were compared between groups. The baseline characteristics were similar between the 2 groups, except for the proportion of men and nonsmokers and body mass index, which were greater in patients treated with bivalirudin. The rate of major bleeding was similar between the bivalirudin and UFH groups (3.4% vs 3.1%, respectively, p = 0.9). The rate of the composite end point (death, Q-wave myocardial infarction, urgent target vessel revascularization) was not significantly different between the 2 groups (1.8% for bivalirudin vs 0.8% for UFH group, p = 0.7). After adjustment, bivalirudin use was not associated with major bleeding (odds ratio 1.23, 95% confidence interval 0.37 to 4.13, p = 0.7). In conclusion, a dose-adjusted bivalirudin anticoagulation regimen for patients requiring chronic dialysis undergoing PCI seems to be as safe and as effective as UFH use alone. These results do not suggest the superiority of bivalirudin over UFH.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Drug Therapy, Combination; Female; Hemorrhage; Heparin; Hirudins; Humans; Inpatients; Kidney Failure, Chronic; Male; Peptide Fragments; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Risk Factors; Treatment Outcome

Patients on dialysis constitute a major healthcare burden with high prevalence of coronary artery disease frequently requiring coronary revascularization. Prior studies have reported high complications rates with revascularization in patients on dialysis. However, information on the use glycoprotein and direct thrombin inhibitors in this patient population undergoing percutaneous revascularization is limited. We retrospectively analyzed the procedural success and in-hospital outcomes of percutaneous coronary revascularization in 56 consecutive patients on dialysis compared with 524 patients without renal failure, between January 2001 and August 2007 at our facility. Additionally, we also analyzed the off-label use of glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors during revascularization in this high-risk group of patients to evaluate for possible increased bleeding complications. In the study group, 7 interventions were performed on peritoneal dialysis and 49 on hemodialysis patients. Sixty-one percent of these patients had diabetes mellitus. A total of 72 lesions were intervened upon; 12 underwent angioplasty and 60 underwent stenting. Four of 72 interventions were not successful, giving a procedural success rate of 94%. There were 6 immediate complications (10.7%), but no deaths. Thirty-two patients (57%) received GP IIb/IIIa inhibitors while direct thrombin inhibitors were used during percutaneous coronary intervention in 11(20%) patients. There were no bleeding complications with use of either GP IIb/IIIa inhibitors or direct thrombin inhibitors. In our experience, percutaneous coronary intervention has high procedural success in dialysis patients and concomitant use of GP IIb/IIIa inhibitors is not associated with any major bleeding complications, making this a feasible, safe and effective revascularization option for patients on dialysis; however, this merits further study in a randomized prospective trial.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Combined Modality Therapy; Coronary Artery Disease; Female; Hirudins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Risk Factors; Treatment Outcome

Unfractionated heparin has been a near universal anticoagulant for cardiac surgery; however it is contraindicated in heparin-induced thrombocytopenia type II. Alternative anticoagulants such as bivalirudin (a direct thrombin inhibitor) are being utilized. Bivalirudin was successfully used in an immunologically complex patient (diagnoses of heparin-induced thrombocytopenia type II, systemic lupus erythematosus, antiphospholipid syndrome, and dialysis-dependent renal failure) requiring cardiopulmonary bypass. Thrombotic events are common in antiphospholipid syndrome patients undergoing cardiac surgery utilizing high-dose heparin. This may represent unrecognized heparin-induced thrombocytopenia type II. Our patient did not experience perioperative thrombotic or bleeding complications. The possible cross-reactivity between heparin induced thrombocytopenia type II and antiphospholipid syndrome has not been investigated.

Topics: Adult; Antibody Specificity; Anticoagulants; Antiphospholipid Syndrome; Autoantibodies; Cross Reactions; Drug Evaluation; Drug Therapy, Combination; Female; Heart Failure; Heparin; Hirudins; Humans; Hypertension, Pulmonary; Kidney Failure, Chronic; Lupus Erythematosus, Systemic; Mitral Valve Insufficiency; Peptide Fragments; Platelet Count; Platelet Factor 4; Recombinant Proteins; Renal Dialysis; Thrombocytopenia; Thrombophilia; Warfarin

Chronic kidney disease is associated with an increased risk of ischemic and bleeding complications after percutaneous coronary intervention (PCI). Bivalirudin, a direct thrombin inhibitor, has been shown to reduce adverse bleeding events compared to unfractionated heparin in patients undergoing PCI. However, the effect of diminished renal function on the safety and efficacy of bivalirudin for PCI is unknown. We aimed to test the safety of bivalirudin in routine practice and to assess whether this benefit was influenced by renal function.. The interaction between renal impairment and benefit from bivalirudin was assessed in 115 consecutive patients (age 68.5+/-12.1, 45% female) undergoing PCI. Bivalirudin dosing was adjusted based on renal function. Creatinine clearance (CrCl) was calculated using the Cockroft-Gault formula. The composite endpoints of in-hospital death, myocardial infarction or revascularization and bleeding events were assessed. Overall, these events occurred in 10 (8.7%) patients. Patients with a CrCl<60 ml/min had a significantly increased risk for in-hospital complications (18.6 versus 2.78%, P = 0.011). Univariate analysis for MACE and bleeding were significant for CrCl<60 ml/min OR: 2.54 (95% CI: 1.61-39.7, P = 0.011), age OR: 3.29 (95% CI: 1.07-1.39, P<0.001) and female gender OR: 2.1 (95% CI: 0.036-0.89, P = 0.036). Risk of complications increased with decreasing renal function: 2.7, 14.2, and 37.5% for CrCl of >60, 30-60 or <30 ml/min, respectively, P = 0.002).. Advanced age, renal dysfunction, and female gender remain important risk factors for ischemic and bleeding complications in patients undergoing PCI with bivalirudin.

Topics: Aged; Angioplasty, Balloon, Coronary; Antithrombins; Comorbidity; Coronary Disease; Creatinine; Female; Hemorrhage; Hirudins; Humans; Kidney Failure, Chronic; Kidney Function Tests; Male; Middle Aged; Peptide Fragments; Prospective Studies; Recombinant Proteins; Risk Factors