bivalirudin and Kidney-Diseases

Chronic kidney disease (CKD) is prevalent and affects an ever-increasing proportion of patients presenting with acute coronary syndrome (ACS). Patients with CKD have a higher risk of ACS and significantly higher mortality, and are also predisposed to increased bleeding complications. Antiplatelet and antithrombotic drugs form the bedrock of management of patients with ACS. Most randomized trials of these drugs exclude patients with CKD, and current guidelines for management of these patients are largely based on these trials. We aim to review the safety and efficacy of these drugs in patients with CKD presenting with ACS.

Topics: Acute Coronary Syndrome; Adenosine; Aspirin; Chronic Disease; Clinical Trials as Topic; Clopidogrel; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Heparin; Hirudins; Humans; Kidney Diseases; Peptide Fragments; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Polysaccharides; Prasugrel Hydrochloride; Recombinant Proteins; Thiophenes; Ticagrelor; Ticlopidine; Uremia

This study sought to investigate the impact of chronic kidney disease (CKD) in patients undergoing percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) with different antithrombotic strategies.. CKD is associated with increased risk of adverse ischemic and hemorrhagic events after primary PCI for STEMI.. HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial was a multicenter, international, randomized trial comparing bivalirudin monotherapy or heparin plus a glycoprotein IIb/IIIa inhibitor (GPI) during primary PCI in STEMI. CKD, defined as creatinine clearance <60 ml/min, was present at baseline in 554 of 3,397 patients (16.3%). Patients were followed for 3 years. Net adverse cardiac event (NACE) was defined as the composite of death, reinfarction, ischemia-driven target vessel revascularization (TVR), stroke or non-coronary artery bypass grafting (CABG)-related major bleeding.. Patients with CKD compared with patients without had higher rates of NACE (41.4% vs. 23.8%, p < 0.0001), death (18.7% vs. 4.4%, p < 0.0001), and major bleeding (19.3% vs. 6.7%, p < 0.0001). Multivariable analysis identified baseline creatinine as an independent predictor of death at 3 years (hazard ratio: 1.51, 95% confidence interval: 1.21 to 1.87, p < 0.001). Patients with CKD randomized to bivalirudin monotherapy versus heparin plus GPI had no significant difference in major bleeding (19.0% vs. 19.6%, p = 0.72) or death (19.0% vs. 18.4%, p = 0.88) at 3 years. In patients with CKD, there was no difference in the rates of TVR in bare-metal stents (BMS) versus drug-eluting stents (DES) at 3 years (14.1% vs. 15.1%, p = 0.8).. STEMI patients with CKD have significantly higher rates of death and major bleeding compared with those without CKD. In patients with CKD, there appears to be no benefit of bivalirudin compared with heparin + GPI, or DES versus BMS during primary PCI in improving clinical outcomes.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Chi-Square Distribution; Chronic Disease; Drug-Eluting Stents; Europe; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Israel; Kaplan-Meier Estimate; Kidney Diseases; Male; Metals; Middle Aged; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Proportional Hazards Models; Prospective Studies; Prosthesis Design; Recombinant Proteins; Recurrence; Risk Assessment; Risk Factors; Stents; Stroke; Thrombosis; Time Factors; Treatment Outcome; United States

In this substudy of the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial, we investigated the relationship between chronic kidney disease (CKD) and clinical outcomes, and compared the safety and efficacy of bivalirudin monotherapy versus heparin plus a glycoprotein IIb/IIIa inhibitor (GPI).. CKD is an important predictor of prognosis in the general population. The outcomes of patients with CKD and acute coronary syndromes (ACS) have not been well studied.. In the ACUITY study, 13,819 patients with moderate- and high-risk ACS undergoing an early, invasive strategy were randomly assigned to 1 of 3 antithrombin regimens: a heparin plus a GPI, bivalirudin plus a GPI, or bivalirudin monotherapy. CKD (creatinine clearance <60 ml/min) was present in 2,469 (19.1%) of 12,939 randomized patients with baseline creatinine clearance data.. Patients with CKD had worse 30-day and 1-year clinical outcomes than those with normal renal function. There were no significant differences between bivalirudin monotherapy and heparin plus a GPI in rates of 30-day composite ischemia (11.1% vs. 9.4%, p = 0.27) and net clinical adverse outcomes (16.1% vs. 16.9%, p = 0.65). There was remarkably less major bleeding (6.2% vs. 9.8%, p = 0.008) at 30 days, but no significant difference in 1-year composite ischemia (22.0% vs. 18.9%, p = 0.10) or mortality (7.1% vs. 7.3%, p = 0.96).. In patients with ACS, CKD is associated with higher 30-day and 1-year adverse event rates. Compared with heparin plus a GPI, the use of bivalirudin monotherapy in patients with CKD results in nonstatistically different ischemic outcomes, but significantly less 30-day major bleeding.

Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Biomarkers; Chronic Disease; Coronary Artery Bypass; Creatinine; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Kidney Diseases; Logistic Models; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Odds Ratio; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prospective Studies; Recombinant Proteins; Risk Assessment; Time Factors; Treatment Outcome; Triage

To evaluate the safety, effectiveness, and dosing of bivalirudin for treatment of heparin-induced thrombocytopenia (HIT) in critically ill patients with hepatic and/or renal dysfunction.. Retrospective cohort study.. University-affiliated medical center. Eighteen patients older than 18 years who were admitted to the intensive care unit (ICU), had hepatic and/or renal dysfunction, and were treated with bivalirudin for the diagnosis of HIT between January 1, 2004, and March 31, 2005.. Patient records were reviewed for dosage and duration of bivalirudin therapy, occurrence of thrombosis, and clinically significant adverse effects. Of the 18 patients identified, 12 had both hepatic and renal dysfunction (group 1), four had hepatic dysfunction (group 2), and two had renal dysfunction (group 3). Demographics were similar among the groups. Mean +/- SD age was 54 +/- 15 years and weight was 82 +/- 14 kg, 67% were male, 83% were Caucasian, and 56% were receiving renal replacement therapy. Mean bivalirudin doses were 0.06 +/- 0.15 mg/kg/hour (median 0.03 mg/kg/hr), 0.14 +/- 0.05 mg/kg/hour (median 0.14 mg/kg/hr), and 0.05 +/- 0.01 mg/kg/hour (median 0.05 mg/kg/hr) for patients in groups 1, 2, and 3, respectively. Ten patients receiving continuous venovenous hemofiltration with or without dialysis received a mean dose of 0.04 +/- 0.03 mg/kg/hour (median 0.03 mg/kg/hr). In the 18 patients, mean bivalirudin duration was 15 +/- 17 days, activated partial thromboplastin time (aPTT) was 69 +/- 22 seconds, and international normalized ratio was 2.2 +/- 0.8. Supratherapeutic aPTTs were most common on days 1 (22%) and 2 (28%) when bivalirudin doses were highest. Clinically significant bleeding did not occur in any patient. Thrombosis occurred in one patient (6%) while receiving bivalirudin.. Patients in the ICU who have hepatic and/or renal dysfunction require low doses of bivalirudin to achieve aPTT values 1.5-2.5 times baseline. Bivalirudin can be safely started at 0.14 mg/kg/hour in patients with hepatic dysfunction, 0.03-0.05 mg/kg/hour in those with renal or combined hepatic and renal dysfunction, and 0.03-0.04 mg/kg/hour in patients receiving continuous renal replacement therapy.

Topics: Adult; Aged; Anticoagulants; Cohort Studies; Critical Illness; Female; Heparin; Hirudins; Humans; Intensive Care Units; Kidney Diseases; Liver Diseases; Male; Middle Aged; Partial Thromboplastin Time; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Thrombin; Thrombocytopenia

The number of patients with coexisting chronic kidney disease (CKD) and cardiovascular disease is growing rapidly. Treatment of these patients is challenging, primarily because of a lack of pharmacokinetic and clinical trial data associated with these combined disease entities. In this report, we discuss the cardiovascular disease risk associated with CKD and review the use of anticoagulation for acute cardiovascular disease in patients with CKD. We evaluate the potential role of direct thrombin inhibitors in patients with renal disease who have acute coronary syndromes, with particular focus on the clinical efficacy of bivalirudin. We conclude that direct thrombin inhibitors, including bivalirudin and argatroban, may be promising alternatives to heparin in patients who have renal insufficiency and are therefore at an increased risk for bleeding. In the treatment of patients with advanced renal insufficiency and cardiovascular disease, however, these agents should be used with dose modification to account for altered excretion.

Topics: Anticoagulants; Antithrombins; Arginine; Chronic Disease; Coronary Disease; Heparin; Heparin, Low-Molecular-Weight; Hirudin Therapy; Hirudins; Humans; Kidney Diseases; Peptide Fragments; Pipecolic Acids; Recombinant Proteins; Sulfonamides; United States