bivalirudin and Cerebrovascular-Disorders

Bivalirudin (Angiomax) is a direct thrombin inhibitor used in interventional cardiology due to its several distinct advantages over heparin, most notably a shorter half-life and a potentially superior safety profile. Bivalirudin is also safe to use in patients with active or remote heparin-induced thrombocytopenia. Our objective was to evaluate the safety and tolerability of high-intensity anticoagulation using bivalirudin during neuroendovascular procedures.. The bivalirudin dosing regimens reported in the cardiac literature were modified empirically for two different activated clotting time (ACT) target ranges. The low-dose protocol (ACT of 250 to 300 s) was used for embolization procedures and the high-dose protocol (ACT of 300-350) was employed for angioplasty and stent placement. The bivalirudin treated patients were matched for age, gender, and type of procedure with a random sample of patients who underwent neuroendovascular procedures with the standardized heparin protocol. The thromboembolic and hemorrhagic complications were compared between the two groups and bleeding complications were categorized as major (hemorrhage that was intra-cerebral or resulted in Hb decrease ≥ 5 g/dl), minor, or insignificant.. Bivalirudin was used in 30 patients with high-dose and low-dose bivalirudin protocols used in 26 and 4 patients, respectively. These were compared to the 60 control patients who received heparin. There were no bleeding or thromboembolic complications in the bivalirudin treated patients; however one patient reported a transient headache. In patients treated with heparin, one bleeding complication of a groin hematoma was reported. Also one patient was found to have left-arm weakness following the procedure which was attributed to a new small middle cerebral artery ischemic event.. Our data supports that bivalirudin usage is likely a safe alternative to heparin for high-intensity anticoagulation in neuroendovascular procedures. Further studies are required for more definitive comparisons for efficacy and cost-effectiveness between the two agents.

Topics: Aged; Angioplasty; Antithrombins; Blood Vessel Prosthesis Implantation; Cerebrovascular Disorders; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Recombinant Proteins; Stents; Treatment Outcome

Worldwide, streptokinase continues to be used widely in the treatment of myocardial infarction because it is inexpensive and causes fewer intracranial hemorrhages than other thrombolytic regimens. However, in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO-I) trial, the 90-minute angiographic Thrombolysis in Myocardial Infarction (TIMI) trial grade 3 flow rate with streptokinase was 43% lower than that with accelerated tissue plasminogen activator, and there was a higher incidence of death or disabling stroke with streptokinase (7.8% vs 6.9%, p <0.01). In the first Hirulog and Early Reperfusion/Occlusion (HERO-1) trial, 48% of patients given the direct thrombin inhibitor bivalirudin (formerly Hirulog, The Medicines Company) after streptokinase had TIMI 3 patency at 90 minutes, compared with 35% of patients given intravenous heparin (p <0.05). Other angiographic and clinical studies and animal research have shown that early infarct artery blood flow may be increased markedly if a direct thrombin inhibitor is administered before the thrombolytic agent. In the HERO-2 trial, 17,000 patients presenting within 6 hours after the onset of acute myocardial infarction will be given aspirin and randomized to receive either intravenous heparin or bivalirudin before streptokinase is administered. The primary endpoint will be 30-day mortality, and secondary endpoints will include death or myocardial infarction within 30 days, and death or nonfatal disabling stroke. If the thrombin hypothesis is supported by improved clinical outcomes with bivalirudin in the HERO-2 trial, large-scale clinical trials will be needed to evaluate the administration of direct thrombin inhibitors before other thrombolytic regimens.

Topics: Antithrombins; Cerebral Hemorrhage; Cerebrovascular Disorders; Coronary Angiography; Drug Therapy, Combination; Fibrinolytic Agents; Heparin; Hirudin Therapy; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Research Design; Streptokinase

This study sought to investigate the clinical outcomes of patients with and without peripheral artery disease (PAD) in the BRAVO-3 trial with respect to the effect of bivalirudin versus unfractionated heparin (UFH).. PAD is found frequently in patients undergoing transcatheter aortic valve replacement (TAVR) and is reported to confer an increased risk of adverse events. It is unknown whether patients with and without PAD may demonstrate a differential response to bivalirudin versus UFH.. BRAVO-3 was a randomized multicenter trial comparing transfemoral TAVR with bivalirudin versus UFH (31 centers, n = 802). Major adverse cardiovascular events (MACE) were a composite of 30-day death, myocardial infarction, or cerebrovascular accidents (CVA). Net adverse cardiovascular events (NACE) were a composite of major bleeding or MACE.. The total cohort included 119 patients with PAD. Vascular complications occurred significantly more frequently in patients with PAD both in-hospital (25.2 vs. 16.7%; OR 1.68) and at 30 days (29.4 vs. 17.3%; OR 1.99). No significant differences were observed regarding mortality, NACE, MACE, major bleeding or CVA with bivalirudin versus UFH among patients with or without PAD. In patients with PAD, bivalirudin was associated with an increased risk of minor vascular complications at 30 days.. Patients with PAD undergoing transfemoral TAVR did not exhibit an increased risk of any major adverse events, according to the procedural anticoagulant randomization. However, patients treated with Bivalirudin had significantly higher rates of minor vascular complications.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Aortic Valve Stenosis; Catheterization, Peripheral; Cerebrovascular Disorders; Europe; Female; Femoral Artery; Hemorrhage; Heparin; Hirudins; Hospital Mortality; Humans; Male; Myocardial Infarction; North America; Peptide Fragments; Peripheral Arterial Disease; Punctures; Randomized Controlled Trials as Topic; Recombinant Proteins; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Transcatheter Aortic Valve Replacement; Treatment Outcome

To evaluate the clinical, angiographic, and cardiac magnetic resonance imaging (cMRI) results in patients with and without diabetes mellitus (DM) undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI).. DM has been associated with increased mortality in patients with STEMI, yet the mechanisms underpinning this association have not been completely elucidated.. Overall, 451 patients (51 diabetics) from the INFUSE-AMI trial were studied. They presented with an anterior STEMI due to an occluded left anterior descending artery (LAD) and underwent bivalirudin-supported primary PCI with or without intralesion abciximab and with or without thrombus aspiration. Angiographic baseline and post-procedure parameters, cMRI at 30 days, and clinical follow-up at 30 days and at 1 year were compared between diabetic and nondiabetic patients.. Patients with DM had significantly more comorbidities and more extensive LAD disease than nondiabetics. Primary PCI was equally effective in restoring coronary flow in both groups and the infarct size at 30 days was similar (14.3% [7.1, 24.5] vs. 17.3% [8.1, 23.6], respectively, P = 0.55). Diabetic patients had more major cardiovascular and cerebrovascular events at 1 year (16.5% vs. 8.0%, P = 0.04). Stent thrombosis within 30 days after primary PCI was higher in diabetic than in nondiabetic subjects (4.3% vs. 0.8%, P = 0.03).. Patients with DM presenting with STEMI had a higher baseline risk profile than those without DM. Although reperfusion success and infarct size were similar, diabetic patients experienced more death, reinfarction, stent thrombosis, and revascularization than nondiabetics.

Topics: Abciximab; Aged; Anterior Wall Myocardial Infarction; Antibodies, Monoclonal; Antithrombins; Cerebrovascular Disorders; Coronary Angiography; Coronary Thrombosis; Diabetes Complications; Female; Hirudins; Humans; Immunoglobulin Fab Fragments; Magnetic Resonance Imaging; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Recombinant Proteins; Recurrence; Retrospective Studies; Risk Assessment; Risk Factors; Suction; Time Factors; Treatment Outcome

We conducted a study using diffusion-weighted (DWI) and perfusion-weighted (PWI) magnetic resonance imaging (MRI) to evaluate the efficacy of thrombolysis in an embolic stroke model with recombinant tissue plasminogen activator (rt-PA) and hirulog, a novel direct-acting antithrombin. DWI can identify areas of ischemia minutes from stroke onset, while PWI identifies regions of impaired blood flow. Right internal carotid arteries of 36 rabbits were embolized using aged heterologous thrombi. Baseline DWI and PWI scans were obtained to confirm successful embolization. Four animals with no observable DWI lesion on the initial scan were excluded; therefore, a total of 32 animals were randomized to one of three treatment groups: rt-PA (n = 11), rt-PA plus hirulog (n = 11), or placebo (n = 10). Treatment was begun 1 h after stroke induction. Intravenous doses were as follows: rt-PA, 5 mg/kg over 0.5 h with 20% of the total dose given as a bolus; hirulog, 1 mg/kg bolus followed by 5 mg/kg over 1 h. MRI was performed at 2, 3, and 5 h following embolization. Six hours after embolization, brains were harvested, examined for hemorrhage, then prepared for histologic analysis. The rt-PA decreased fibrinogen levels by 73%, and hirulog prolonged the aPTT to four times the control value. Posttreatment areas of diffusion abnormality and perfusion delay were expressed as a ratio of baseline values. Significantly improved perfusion was seen in the rt-PA plus hirulog group compared with placebo (normalized ratios of the perfusion delay areas were as follows: placebo, 1.58, 0.47-3.59; rt-PA, 1.12, 0.04-3.95; rt-PA and hirulog, 0.40, 0.02-1.08; p < 0.05). Comparison of diffusion abnormality ratios measured at 5 h showed trends favoring reduced lesion size in both groups given rt-PA (normalized ratios of diffusion abnormality areas were as follows: placebo, 3.69, 0.39-15.71; rt-PA, 2.57, 0.74-5.00; rt-PA and hirulog, 1.95, 0.33-6.80; p = 0.32). Significant cerebral hemorrhage was observed in one placebo, two rt-PA, and three rt-PA plus hirulog treated animals. One fatal systemic hemorrhage was observed in each of the rt-PA groups. We conclude that rt-PA plus hirulog improves cerebral perfusion but does not necessarily reduce cerebral injury. DWI and PWI are useful methods for monitoring thrombolysis.

Topics: Animals; Anticoagulants; Blood Coagulation; Brain; Cerebral Hemorrhage; Cerebrovascular Circulation; Cerebrovascular Disorders; Hirudins; Intracranial Embolism and Thrombosis; Male; Peptide Fragments; Plasminogen Activators; Rabbits; Recombinant Proteins; Tissue Plasminogen Activator