bivalirudin and Acute-Kidney-Injury

Acute kidney injury (AKI) is a critical complication among patients with acute coronary syndrome (ACS) undergoing invasive management. The value of adjunctive antithrombotic strategies, such as bivalirudin or unfractionated heparin (UFH) on the risk of AKI is unclear.. Among 7213 patients enrolled in the MATRIX-Antithrombin and Treatment Duration study, 128 subjects were excluded due to incomplete information on serum creatinine (sCr) or end-stage renal disease on dialysis treatment. The primary endpoint was AKI defined as an absolute (>0.5 mg/dL) or a relative (>25%) increase in sCr. AKI occurred in 601 patients (16.9%) treated with bivalirudin and 616 patients (17.4%) treated with UFH [odds ratio (OR): 0.97; 95% confidence interval (CI): 0.85-1.09; P = 0.58]. A >25% sCr increase was observed in 597 patients (16.8%) with bivalirudin and 616 patients (17.4%) with UFH (OR: 0.96; 95% CI: 0.85-1.08; P = 0.50), whereas a >0.5 mg/dL absolute sCr increase occurred in 176 patients (5.0%) with bivalirudin vs. 189 patients (5.4%) with UFH (OR: 0.92; 95% CI: 0.75-1.14; P = 0.46). By implementing the Kidney Disease Improving Global Outcomes (KDIGO) criteria, the risk of AKI was not significantly different between bivalirudin and UFH groups (OR: 0.88; 95% CI: 0.72-1.07; P = 0.21). Subgroup analyses of the primary endpoint suggested a benefit with bivalirudin in patients randomized to femoral access.. Among ACS patients undergoing invasive management, the risk of AKI was not significantly lower with bivalirudin compared with UFH.. clinicaltrials.gov NCT01433627.

Topics: Acute Coronary Syndrome; Acute Kidney Injury; Heparin; Hirudins; Humans; Peptide Fragments; Recombinant Proteins

Acute kidney injury (AKI) is not uncommon in patients undergoing transcatheter aortic valve replacement (TAVR).. We examined the incidence, predictors, and outcomes of AKI from the BRAVO 3 randomized trial.. The BRAVO-3 trial included 802 patients undergoing transfemoral TAVR randomized to bivalirudin vs. unfractionated heparin (UFH). The primary endpoint of the trial was Bleeding Academic Research Consortium (BARC) type ≥ 3b bleeding at 48 h. Total follow-up was to 30 days. AKI was adjudicated using the modified RIFLE (Valve Academic Research Consortium, VARC 1) criteria through 30-day follow-up, and in a sensitivity analysis AKI was assessed at 7 days (modified VARC-2 criteria). We examined the incidence, predictors, and 30-day outcomes associated with diagnosis of AKI. We also examined the effect of procedural anticoagulant (bivalirudin or unfractionated heparin, UFH) on AKI within 48 h after TAVR.. The trial population had a mean age of 82.3 ± 6.5 years including 48.8% women with mean EuroScore I 17.05 ± 10.3%. AKI occurred in 17.0% during 30-day follow-up and was associated with greater adjusted risk of 30-day death (13.0% vs. 3.5%, OR 5.84, 95% CI 2.62-12.99) and a trend for more BARC ≥ 3b bleeding (15.1% vs. 8.6%, OR 1.80, 95% CI 0.99-3.25). Predictors of 30-day AKI were baseline hemoglobin, body weight, and pre-existing coronary disease. AKI occurred in 10.7% at 7 days and was associated with significantly greater risk of 30-day death (OR 6.99, 95% CI 2.85-17.15). Independent predictors of AKI within 7 days included pre-existing coronary or cerebrovascular disease, chronic kidney disease (CKD), and transfusion which increased risk, whereas post-dilation was protective. The incidence of 48-h AKI was higher with bivalirudin compared to UFH in the intention to treat cohort (10.9% vs. 6.5%, p = 0.03), but not in the per-protocol assessment (10.7% vs. 7.1%, p = 0.08).. In the BRAVO 3 trial, AKI occurred in 17% at 30 days and in 10.7% at 7 days. AKI was associated with a significantly greater adjusted risk for 30-day death. Multivariate predictors of AKI at 30 days included baseline hemoglobin, body weight, and prior coronary artery disease, and predictors at 7 days included pre-existing vascular disease, CKD, transfusion, and valve post-dilation. Bivalirudin was associated with greater AKI within 48 h in the intention to treat but not in the per-protocol analysis.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Female; Follow-Up Studies; Hemorrhage; Heparin; Hirudins; Humans; Incidence; Male; Peptide Fragments; Postoperative Complications; Recombinant Proteins; Time Factors; Transcatheter Aortic Valve Replacement

Acute kidney injury (AKI) is an important complication of both diagnostic cardiac catheterization and percutaneous coronary intervention (PCI). A large body of evidence supports that AKI is related to volume of contrast used. Despite several measures are available to reduce the impact of contrast media on AKI, its incidence remains significant as other mechanisms of renal damage are involved. A new paradigm is established according to which bleeding prevention is at least as important as preventing recurrent ischemic events in the management of patients with acute coronary syndromes (ACS) undergoing an invasive approach. Periprocedural bleeding, which is consistently reduced by radial approach, is emerging as a risk factor for the development of AKI. Therefore, the role of vascular access as a measure to prevent AKI needs to be systematically assessed in randomized studies. To date, no prospective comparison on renal outcomes has been carried out in randomized trials between radial and femoral approach. The Minimizing Adverse hemorrhagic events by TRansradial access site and systemic Implementation of AngioX (MATRIX) trial (ClinicalTrials.gov identifier: NCT01433627) has been designed to test whether to minimize bleeding events by using radial access and bivalirudin, across the whole spectrum of patients with ACS undergoing PCI, will result in improved outcomes with respect to both ischemic and bleeding complications. The AKI-MATRIX sub-study will provide a unique opportunity to assess whether the advantages of radial approach may even contribute to the reduction of the risk of AKI in patients with ACS.

Topics: Acute Coronary Syndrome; Acute Kidney Injury; Antithrombins; Catheterization, Peripheral; Clinical Protocols; Contrast Media; Coronary Angiography; Hemorrhage; Hirudins; Humans; Incidence; Peptide Fragments; Percutaneous Coronary Intervention; Prospective Studies; Punctures; Radial Artery; Recombinant Proteins; Research Design; Risk Factors; Time Factors; Treatment Outcome

To evaluate the safety and efficacy of bivalirudin compared with heparin for preventing hemofilter occlusion during continuous venovenous hemofiltration (CVVH).. Prospective, randomized, double-blind study.. University-affiliated hospital.. Ten critically ill adults (median age 58 yrs, 70% male) with acute renal failure who, without anticoagulation, experienced hemofilter survival time of 24 hours or less during CVVH.. Patients were randomized to receive bivalirudin 2 mg/hour (five patients) or heparin 400 units/hour (five patients) administered prefilter into the extracorporeal circuit.. Patients had a median Acute Physiology and Chronic Health Evaluation (APACHE) II score of 24, Sequential Organ Failure Assessment (SOFA) score of 11, and reduced antithrombin activity (75.5 units/dl). Baseline characteristics were not significantly different between groups. Study drug was administered in 40 hemofilters (18 from bivalirudin-treated patients, 22 from heparin-treated patients). The primary efficacy outcome was hemofilter survival time, defined as the interval of time between commencement of CVVH with a new extracorporeal circuit (hemofilter) and hemofilter failure. Compared with no anticoagulation, the addition of bivalirudin or heparin significantly improved hemofilter survival time (mean ± SD 10 ± 5 hrs with no anticoagulation vs 22 ± 18 hrs with anticoagulation, p=0.0005). Hemofilter survival time was significantly increased in patients receiving bivalirudin versus those receiving heparin (29.6 ± 20.7 vs 16.5 ± 13.6 hrs, p=0.045). Independent predictors of hemofilter survival were use of bivalirudin therapy and increased antithrombin III activity. No patients randomized to bivalirudin experienced any bleeding or thrombosis events; one patient who received heparin developed alveolar hemorrhage, and one developed a lower extremity deep vein thrombosis.. Compared with heparin, bivalirudin was more efficacious in prolonging hemofilter survival time and was well tolerated. Additional studies of bivalirudin for prevention of hemofilter occlusion during continuous renal replacement therapy are warranted.

Topics: Acute Kidney Injury; Anticoagulants; Antithrombins; Critical Illness; Double-Blind Method; Female; Hemofiltration; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Prospective Studies; Recombinant Proteins; Time Factors

As patients transition between dialysis modalities, and from the intra- to the inter-dialytic period, medications with a narrow therapeutic index that are cleared in dialysis may require dose adjustments and close monitoring. Three cases of patients receiving bivalirudin while converting from continuous to prolonged intermittent renal replacement therapy are reported. Details provided include flow rates and ultrafiltrate volume. In these cases, it appears pre-emptive dose adjustments may be unwarranted, and clinicians should be aware of potential rebound after cessation of dialysis.

Topics: Acute Kidney Injury; Hirudins; Humans; Intermittent Renal Replacement Therapy; Peptide Fragments; Recombinant Proteins; Renal Dialysis

Patients with a previous history of heparin-induced thrombocytopenia are at a higher risk for thromboembolic events, and heparin administration is formally contraindicated. Bivalirudin has been reported as an alternative therapy whenever an intervention that requires systemic anticoagulation and cardiopulmonary by-pass pump is needed. We present the case of a patient diagnosed with heparin-induced thrombocytopenia and heparin-PF4 (+) antibodies requiring a triple cardiac valve replacement who developed fulminant coagulopathy after bivalirudin administration. A discussion on the serious difficulties that the management of these types of patients involves, as well as a review of prevention strategies are presented.

Topics: Acute Kidney Injury; Aged; Anticoagulants; Antithrombins; Blood Loss, Surgical; Coronary Artery Bypass; Disseminated Intravascular Coagulation; Drug Substitution; Fatal Outcome; Heart Failure; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Heparin; Hirudins; Humans; Immunoglobulin G; Intraoperative Complications; Male; Multiple Organ Failure; Peptide Fragments; Platelet Factor 4; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Thrombophilia

To describe a case of successful bivalirudin use as a prefilter anticoagulant in continuous venovenous hemofiltration (CVVH).. A 30-year-old male was brought to the hospital by ambulance with an anterior communicating artery subarachnoid hemorrhage, signs of intraparenchymal hemorrhage, and hydrocephalus. During the patient's complicated hospital course, he developed acute renal failure requiring CVVH, as well as hepatic insufficiency (Child-Pugh class B). Unfractionated heparin was used as a prefilter anticoagulant. After he had a positive heparin-induced thrombocytopenia (HIT) antibody test, prefilter heparin was discontinued in favor of bivalirudin. Filter survival and systemic activated partial thromboplastin time (aPTT) values were compared between prefilter heparin (n = 5) and bivalirudin (n = 4). Filter survival was similar (median 26 h with heparin vs 37 h with bivalirudin; p = 0.52). Prefilter bivalirudin 1-2.5 mg/hour (0.009-0.023 mg/kg/h) was effective in maintaining systemic aPTTs that were 1-1.4 times the reference range. Serotonin release assay and subsequent HIT antibodies were negative. The patient's renal function improved and CVVH was discontinued.. Critically ill patients requiring CVVH often need regional or systemic anticoagulation to prevent filter occlusion. In some patient populations, such as those with HIT or liver failure, prefilter heparin and regional citrate, respectively, may not be options. Alternative anticoagulants may be needed to avoid complications of frequent filter occlusions. The direct thrombin inhibitors (DTIs) lepirudin and argatroban have been used to maintain hemofilter patency, in small studies. Bivalirudin may have pharmacokinetic advantages over other DTIs when used in patients with hepatic and renal impairment. In our patient, bivalirudin provided a safe alternative to heparin therapy and was effective in maintaining hemofilter patency during CVVH.. Prefilter bivalirudin may be an option to prevent filter occlusion in patients requiring continuous renal replacement therapy. Future studies are needed to validate the safety and efficacy of bivalirudin as a prefilter anticoagulant.

Topics: Acute Kidney Injury; Adult; Anticoagulants; Hemofiltration; Heparin; Hirudins; Humans; Male; Peptide Fragments; Recombinant Proteins; Thrombocytopenia