bivalirudin and Peripheral-Vascular-Diseases

The direct thrombin inhibitor bivalirudin (BIV) was shown to be superior to unfractionated heparin (UFH) in percutaneous coronary interventions for reducing procedural blood loss. The aim of this study was to compare outcome profiles of BIV and UFH in peripheral endovascular procedures (PEPs) by synthesizing the currently available data.. Following the PRISMA statement, we conducted a comprehensive literature search using Medline, Cochrane CENTRAL, PubMed, EMBASE, CINAHL Google scholar, and clinicaltrials.gov. We recruited randomized, controlled trials and well-conducted observational studies that compared UFH and BIV in PEPs requiring anticoagulation, excluding endovascular cardiac procedures and coronary interventions. Random-effects meta-analyses were conducted to compare the outcome profiles of these two agents.. Thirteen articles containing 14 studies involving a total of 21,057 patients were enrolled. Of these, 2 were randomized controlled trials, 2 were prospective cohort studies, and 10 were retrospective studies. There were no significant differences between BIV and UFH in terms of procedural success rates, major and minor perioperative bleeding, transfusion, perioperative transient ischemic attack, or hemorrhagic strokes. However, compared with UFH, BIV had significantly lower odds ratios (OR) of perioperative mortality (OR, 0.58; 95% confidence interval [CI], 0.40-0.86), major adverse cardiovascular events (OR, 0.65; 95% CI, 0.51-0.83), net adverse clinical events (OR, 0.75; 95% CI, 0.63-0.88), perioperative myocardial infarction (OR, 0.73; 95% CI, 0.55-0.98), major vascular complications (OR, 0.59; 95% CI, 0.39-0.91), and minor vascular complications (OR, 0.58; 95% CI, 0.40-0.84).. Compared with UFH, PEPs using BIV had comparable procedural success rates and odds of perioperative transient ischemic attack and hemorrhagic stroke. However, procedures with BIV had a lower but nonsignificant odds of perioperative bleeding and transfusion. Depending on the procedures conducted, the patients who received BIV will have reduced or comparable odds of perioperative mortality, myocardial infarction, major adverse cardiovascular events, net adverse clinical events, and major and minor vascular complications. Therefore, BIV may be chosen solely as an alternative procedural anticoagulant to UFH for PEPs.

Topics: Anticoagulants; Antithrombins; Endovascular Procedures; Hemorrhage; Heparin; Hirudins; Humans; Ischemic Attack, Transient; Myocardial Infarction; Observational Studies as Topic; Patient Safety; Peptide Fragments; Peripheral Vascular Diseases; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Assessment; Risk Factors; Stroke; Treatment Outcome

A number of studies suggest that bivalirudin (BIV) is associated with similar efficacy but reduced bleeding when compared with unfractionated heparin (UFH) in patients undergoing peripheral vascular interventions (PVI).. A comprehensive literature search was conducted with the electronic databases MEDLINE, EMBASE and CENTRAL. These were queried to identify studies comparing BIV with UFH in PVI. Study endpoints included total bleeding events, major and minor bleeding events and procedural success. Random-effects meta-analysis method was used to pool endpoint odds ratios (OR) for both UFH and BIV with 95% confidence intervals (CI).. A total of 12,335 patients (70.6 years; 59.7% male) were included from seven observational cohort studies (two prospective and five retrospective) comparing outcomes between BIV and UFH during PVI between January 2000 and May 2017. Compared with BIV, UFH was associated with significantly higher total bleeding, (OR 1.52 with 95% CI 1.11 to 2.09, p = 0.009), major bleeding (OR 1.38 with 95% CI 1.13 to 1.68, p = 0.002), and minor bleeding (OR 1.51 with 95% CI 1.09 to 2.08, p = 0.01). Procedural success rates were not different between the two groups (BIV vs HEP: OR 0.90 with 95% CI 0.49 to 1.64, p = 0.72) CONCLUSION: Compared with BIV, UFH was associated with more bleeding when used during PVI. There was no significant difference in procedural success between the two anticoagulation strategies.

Topics: Aged; Anticoagulants; Antithrombins; Endovascular Procedures; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Observational Studies as Topic; Peptide Fragments; Peripheral Vascular Diseases; Recombinant Proteins; Risk Assessment; Risk Factors; Treatment Outcome

Patients undergoing percutaneous peripheral interventions are at increased risk for thrombotic complications hence the routine use of periprocedural anticoagulants. There is currently no American College of Cardiology/American Heart Association guidelines for periprocedural anticoagulants use in percutaneous peripheral interventions. Historically, unfractionated heparin has been the most common periprocedural anticoagulant used during percutaneous peripheral interventions. There may be a role for more predictable periprocedural anticoagulants in percutaneous peripheral interventions as has been demonstrated in percutaneous coronary interventions. Our review focuses on the evidence supporting the use of bivalirudin in percutaneous peripheral interventions.

Topics: Angioplasty; Anticoagulants; Heparin; Hirudins; Humans; Intraoperative Care; Peptide Fragments; Peripheral Vascular Diseases; Recombinant Proteins

Topics: Angiography; Angioplasty, Balloon; Antithrombins; Heparin, Low-Molecular-Weight; Hirudins; Humans; Peptide Fragments; Peripheral Vascular Diseases; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Thrombosis

High-risk patient characteristics and complexity of percutaneous peripheral intervention (PPI) procedures suggest a need for predictable and reliable anticoagulation. We undertook this study to assess the safety and efficacy of bivalirudin as the procedural anticoagulant in patients undergoing PPI of the renal, iliac, or femoral artery.. This was a prospective, open-label, single arm study inpatients undergoing PPI of the renal, iliac, or femoral vessels to assessbivalirudin as the sole procedural anticoagulant (0.75 mg/kg bolus/1.75 mg/kg/hr infusion). The primary endpoint was procedural success defined as residual stenosis < 20%. Secondary endpoints included ischemic events (death, myocardial infarction, unplanned revascularization, and amputation), and bleeding complications, as well as ACT values and times to sheath removal, ambulation, and discharge.. 505 patients were enrolled at 26 sites. Procedural success was achieved in 95.0% of patients. Ischemic events were low (1.4%) and similar between vessel types. Protocol-defined major hemorrhage and TIMI major hemorrhage rates were 2.2% and 0.4%, respectively. Mean ACTs were similar among treatment groups (renal 353.8 seconds(s); iliac 335.9s, femoral, 343.5s).. Bivalirudin provided consistent anticoagulation and similar outcomes in all vessel types treated at the dose tested. Ischemic and bleeding event rates were low, demonstrating the safe use of bivalirudin as a procedural anticoagulant in PPI.

Topics: Aged; Angioplasty, Balloon; Arterial Occlusive Diseases; Catheterization, Peripheral; Combined Modality Therapy; Female; Femoral Artery; Follow-Up Studies; Hirudins; Humans; Iliac Artery; Length of Stay; Male; Middle Aged; Peptide Fragments; Peripheral Vascular Diseases; Prospective Studies; Recombinant Proteins; Renal Artery Obstruction; Risk Assessment; Single-Blind Method; Survival Rate; Time Factors; Treatment Outcome; Vascular Patency

Unfractionated heparin is a widely utilized anticoagulant during peripheral angioplasty procedures (PTA). In contrast to heparin, bivalirudin is a direct thrombin inhibitor with predictable anticoagulation, does not activate platelets, and inhibits both soluble and bound thrombin. The experience with bivalirudin during PTA remains limited. In this single-center prospective study, 48 consecutive patients (60.4% males, mean age 70.0 12.1) received bivalirudin as the primary anticoagulant during PTA (0.75 mg/kg bolus, 1.75 mg/kg/h during the procedure). Thirty-four (70.8%) had claudication and 6 (12.5%) had ulceration. Thrombus was angiographically seen in 3 (6.3%) patients. In-hospital serious procedural complications were limited to 2 (4.2%) (exact 95% confidence interval: (0.5%,14.3%]) patients with major bleeding; none (0.0%) of the other following endpoints occurred: death, limb loss, emergent need for revascularization of the same vessel, embolic strokes, and vascular complications (exact 95% confidence intervals: [0.0%,6.1%]). This compared favorably to previously reported data using unfractionated heparin and the same serious procedural complications endpoints from our group at the same institution (9.2%). We conclude that the use of bivalirudin during PTA appears feasible and safe. Large prospective registries are needed to confirm these findings.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon; Antithrombins; Female; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Peripheral Vascular Diseases; Prospective Studies; Recombinant Proteins

Anticoagulation therapy for cardiopulmonary bypass in patients with recently diagnosed heparin-induced thrombocytopenia can be particularly challenging. Although heparin is the standard of care, in these situations anticoagulation is achieved with alternative agents such as direct thrombin inhibitors. Therapeutic concentrations are difficult to assess with direct thrombin inhibitors, and their use is riddled with bleeding and thrombotic complications. We report the successful use of a specific chromogenic antifactor IIa assay in a patient with heparin-induced thrombocytopenia who received anticoagulation therapy with bivalirudin during cardiopulmonary bypass for coronary artery bypass graft surgery.

Topics: Aged; Antithrombins; Cardiopulmonary Bypass; Coronary Artery Bypass; Dose-Response Relationship, Drug; Drug Administration Schedule; Follow-Up Studies; Heparin; Hirudins; Humans; Infusions, Intravenous; Male; Monitoring, Intraoperative; Myocardial Infarction; Peptide Fragments; Peripheral Vascular Diseases; Preoperative Care; Radiography; Recombinant Proteins; Thrombocytopenia; Treatment Outcome

Topics: Angioplasty; Anticoagulants; Constriction, Pathologic; Hemorrhage; Heparin; Hirudins; Humans; Ischemia; Peptide Fragments; Peripheral Vascular Diseases; Radiography; Recombinant Proteins; Risk Assessment; Risk Factors; Severity of Illness Index; Treatment Outcome

To present real-world data to evaluate the safety and effectiveness of bivalirudin, a direct thrombin inhibitor, in an unselected group of patients undergoing percutaneous peripheral interventions (PPI).. Data were extracted from a prospectively collected peripheral vascular registry developed for quality assurance measures at 2 centers. Of 398 consecutive patients (195 men; mean age 69.4+/-11.3 years) who underwent PPI in a 2-year period, 369 (92.7%) received bivalirudin (0.75 mg/kg bolus followed by a 1.75 mg/kg/h infusion) and 29 (7.3%) received unfractionated heparin (UFH). In the bivalirudin sample, critical limb ischemia was present in 28.0% of patients, TASC D lesion in 29.5%, and angiographic thrombus in 7.8% of vessels. Demographic, clinical, procedural, and angiographic variables and in-hospital complications were analyzed. All in-hospital adverse events were independently adjudicated.. Procedural success (<30% residual narrowing) was achieved in 359 (97.3%) patients receiving bivalirudin. Adverse events included stroke (1, 0.3%), acute renal failure (1, 0.3%), major bleeding (3, 0.8%), distal embolization (11, 3.0%), vascular access complications (2, 0.5%), and minor amputation (2, 0.5%).. Bivalirudin had an excellent safety profile in a real-life cohort of patients undergoing PPI, including high-risk patients with critical limb ischemia and TASC D lesions. In-hospital major bleeding and other adverse events were infrequent. A randomized trial of bivalirudin versus UFH is needed to verify these results and establish bivalirudin as a standard anticoagulant in PPI.

Topics: Aged; Aged, 80 and over; Angioplasty; Anticoagulants; Chi-Square Distribution; Constriction, Pathologic; Female; Hemorrhage; Heparin; Hirudins; Humans; Inpatients; Iowa; Ischemia; Logistic Models; Male; Middle Aged; Peptide Fragments; Peripheral Vascular Diseases; Radiography; Recombinant Proteins; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Treatment Outcome

The aim of this study was to determine the efficacy and safety of bivalirudin versus low-dose unfractionated heparin (UFH) in percutaneous peripheral intervention (PPI).. Anticoagulation strategies used in PPI are based primarily on studies of percutaneous coronary intervention where higher doses of heparin are used usually in combination with a glycoprotein IIb/IIIa inhibitor. There are no studies comparing bivalirudin alone versus low-dose heparin in PPI.. Consecutive patients who underwent PPI at our institution were treated with either bivalirudin or low-dose UFH. Patients were assessed prospectively during index hospital stay for procedural success and bleeding complications. Of 236 patients, 111 were dosed with UFH at 50 U/kg (goal activated clotting time of 180 to 240 s), and 125 were dosed with bivalirudin at 0.75-mg/kg/h bolus followed by a 1.75-mg/kg infusion. Procedural success was defined as <20% post-procedure residual stenosis with no flow-limiting dissections or intravascular thrombus formation and major bleeding as intracranial or retroperitoneal hemorrhage or a fall in hemoglobin >or=5 g/dl. Anticoagulation cost analysis was conducted.. Procedural success and major bleeding rates were similar with bivalirudin versus heparin (98% vs. 99% and 2.4% vs. 0.9%, respectively). There were no differences in minor bleeding, time to ambulation, and length of hospital stay. The hospital cost for bivalirudin was $547 and <$1.22 for heparin (10,000 U). Two activated clotting time levels cost $4.00.. Low-dose UFH is as effective and safe as bivalirudin when used as an anticoagulation strategy in patients undergoing PPI, and low-dose UFH is less costly than bivalirudin. Larger randomized studies are required to further evaluate these findings.

Topics: Aged; Aged, 80 and over; Angioplasty; Anticoagulants; Cost-Benefit Analysis; Drug Costs; Female; Hemorrhage; Heparin; Hirudins; Hospital Costs; Humans; Length of Stay; Male; Middle Aged; Peptide Fragments; Peripheral Vascular Diseases; Prospective Studies; Recombinant Proteins; Stents; Thrombosis; Time Factors; Treatment Outcome; Walking

The combination of glycoprotein (GP) IIb-IIIa inhibition and direct thrombin inhibition (DTI) with bivalirudin (Angiomax, The Medicines Company, Cambridge, Massachusetts) have shown ischemic and hemorrhagic outcomes benefit in coronary interventions and may have similar benefits in percutaneous peripheral interventions (PPI). The high incidence of diabetes, chronic renal disease, platelet dysfunction, hypercoagulability, inflammation and a thrombus-rich environment make a GP IIb-IIIa and DTI combination with tirofiban (Aggrastat Merck and Company, Inc., Whitehouse Station, New Jersey) an attractive anticoagulation strategy in the PPI treatment of critical limb ischemia (CLI).. Between May 1, 2001 and January 31, 2003, a CLI treatment group of 149 patients received PPI with bivalirudin (0.75 mg per kg bolus with 1.75 mg per kg per hour periprocedural infusion) and tirofiban (10 mcg per kg per minute bolus with 12-hour 0.1 mcg per kg per minute infusion) as an anticoagulation and antiplatelet strategy, and were compared to a matched unfractionated heparin (UFH) control group without GP IIb-IIIa inhibitors. Clinical and hemostasis outcomes were analyzed, including distal embolization (DE).. Procedural success was 95.9% and 97.3% in the UFH control group and DTI-GP IIb-IIIa group, respectively. Significant differences were observed in the sheath removal time < 2 hours (60.5% UFH group versus 19.4% DTI-GP IIb-IIIa group; p = < 0.0001). Vascular closure devices were used equally in both groups. No statistical significance was observed in major and minor complications, femoral access complications, acute (< 48 hours) or subacute (30 days) vessel thrombosis, and 6-month duplex ultrasound restenosis rate between the DTI-GP IIb-IIIa versus the UFH group. A trend towards statistical significance was observed in the 6-month secondary re-intervention and limb salvage rates (10.7% versus 18.8%; p = 0.0501 and 93.9% versus 88.5%; p = 0.053) in the DTI-GP IIb-IIIa versus the UFH group, respectively. Angiographically relevant DE occurred in 4 of 149 (1.3%) and 8 of 149 (5.4%) of the bivalirudin-tirofiban and UFH groups, respectively.. The combination of DTI with bivalirudin and GP IIb-IIIa inhibition with tirofiban is a safe and feasible alternative anticoagulation and antiplatelet strategy in PPI, and may offer improved clinical and hemostasis outcomes in treating CLI. A larger, prospective randomized trial is warranted.

Topics: Acute Disease; Aged; Angioplasty, Balloon; Anticoagulants; Feasibility Studies; Female; Follow-Up Studies; Hirudins; Humans; Ischemia; Leg; Male; Myocardial Ischemia; Peptide Fragments; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Retrospective Studies; Thrombin; Tirofiban; Treatment Outcome; Tyrosine

Traditionally, unfractionated heparin is used to prevent thrombotic complications in peripheral interventions. The purpose of this study is to evaluate the use of bivalirudin as the anticoagulant agent for peripheral interventions.. A retrospective analysis of 108 patients who underwent 110 peripheral interventions between January 2002 and January 2004 and received bivalirudin as the sole anticoagulation agent was conducted at Baptist Cardiac and Vascular Institute. Interventions were performed in the following areas: iliac, femoropopliteal, and distal (n = 55), carotid (n = 31), vertebral (n = 1), renal (n = 14), aorta (n = 7), and subclavian (n = 2). The following procedural and clinical endpoints were examined: death, requirement of urgent surgery or surgery during the same admission, urgent percutaneous revascularization in the same treated vessel, thrombotic or embolic events, bleeding events, and groin complications.. A total of 266 lesions were dilated in 185 arteries. There were no procedural mortalities, procedural success was 99.1%, and the complication rate was 3.6%. There was one embolic stroke (0.9%), one thrombosis (0.9%), and two groin hematomas (1.8%). No patient required urgent surgery or reintervention in the same treated vessel. No complications were noted at 7 days after the procedure. There were two interventions by postprocedure day 30: toe amputation and groin debridement.. Bivalirudin is a safe alternative to unfractionated heparin as the anticoagulation agent in peripheral interventions. This study shows that the complication profile is comparable to other bivalirudin studies. Bivalirudin is effective, easy to use, and is associated with few bleeding complications.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aorta; Carotid Artery, Common; Female; Femoral Artery; Florida; Follow-Up Studies; Hirudins; Humans; Iliac Artery; Length of Stay; Male; Middle Aged; Peptide Fragments; Peripheral Vascular Diseases; Popliteal Artery; Postoperative Complications; Recombinant Proteins; Renal Artery; Retrospective Studies; Subclavian Artery; Treatment Outcome; Vascular Surgical Procedures; Vertebral Artery

Many heparin (UFH) limitations are overcome by bivalirudin (Angiomax ). The pharmacokinetic profile of bivalirudin appears well suited for percutaneous peripheral intervention (PPI), yet few data exist regarding its safety and feasibility in this setting.. One hundred and eighty renal and 75 iliac PPIs performed between May 2001 and June 2002 with bivalirudin as anticoagulation were compared to a historical UFH control. Variables evaluated included thrombotic events, intracranial bleeding, major surgical complications, sheath removal time, vascular access complication, time to ambulate and length of stay (LOS). Follow-up included 6-month renal and iliac duplex ultrasound and ankle-brachial index.. Procedural success was achieved in 100% of patients treated with bivalirudin, with no thrombotic events, intracranial bleeding or major surgical complications observed. Procedural success was achieved in 179/180 (99%) renal and 74/75 (98.6%) iliac patients treated with UFH. Significant differences were observed for sheath removal time < 60 minutes (84% versus 59%; p < 0.0001), time to ambulation < 6 hours (75.5% versus 58%; p < 0.0005) and LOS < 24 hours (85.5% versus 72%; p = 0.002) in bivalirudin-treated renal PPI patients versus UFH-treated patients, respectively. Significant differences were also observed in favor of bivalirudin for the iliac PPIs for sheath removal time < 60 minutes (p = 0.012) and time to ambulation < 6 hours (p = 0.039). Following 6-month renal and iliac duplex ultrasound, repeat PPI was required in 7/180 (3.9%) and 9/180 (5%) of renal, and 3/75 (4%) and 4/75 (5.3%) of iliac patients treated with bivalirudin or UFH, respectively.. Bivalirudin is a safe and feasible alternative anticoagulant in renal and iliac PPI and may offer decreased sheath removal time, time to ambulation and LOS. A larger prospective randomized multicenter trial is warranted.

Topics: Aged; Anticoagulants; Arterial Occlusive Diseases; Case-Control Studies; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Heparin, Low-Molecular-Weight; Hirudins; Humans; Iliac Artery; Infusions, Intravenous; Male; Middle Aged; Peptide Fragments; Peripheral Vascular Diseases; Recombinant Proteins; Renal Artery Obstruction; Retrospective Studies; Risk Assessment; Treatment Outcome; Vascular Patency