hirudin and Non-ST-Elevated-Myocardial-Infarction

The benefit:risk profile of bivalirudin versus heparin anticoagulation in patients with non-ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) is uncertain. Study-level meta-analyses lack granularity to provide conclusive answers. We sought to compare the outcomes of bivalirudin and heparin in patients with non-ST-segment-elevation myocardial infarction undergoing PCI.. We performed an individual patient data meta-analysis of patients with non-ST-segment-elevation myocardial infarction in all 5 trials that randomized ≥1000 patients with any myocardial infarction undergoing PCI to bivalirudin versus heparin (MATRIX [Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox], VALIDATE-SWEDEHEART [Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial], ISAR-REACT 4 [Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 4], ACUITY [Acute Catheterization and Urgent Intervention Triage Strategy], and BRIGHT [Bivalirudin in Acute Myocardial Infarction vs Heparin and GPI Plus Heparin Trial]). The primary effectiveness and safety end points were 30-day all-cause mortality and serious bleeding.. In patients with non-ST-segment-elevation myocardial infarction undergoing PCI, procedural anticoagulation with bivalirudin and heparin did not result in significantly different rates of mortality or ischemic events, including stent thrombosis and reinfarction. Bivalirudin reduced serious bleeding compared with heparin arising both from the access site and nonaccess sites.

Topics: Anticoagulants; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recombinant Proteins; Thrombosis; Treatment Outcome

Elderly patients with acute myocardial infarction undergoing percutaneous coronary intervention are at increased risk of both ischemic and bleeding complications. The optimal anticoagulation strategy in these patients is uncertain. Therefore, we compared bivalirudin to heparin monotherapy in a contemporary cohort of such patients.. A prespecified subgroup analysis of elderly patients with myocardial infarction (≥75 years) from the VALIDATE-SWEDEHEART trial (Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial) was performed. In the trial, patients were randomized to either bivalirudin or heparin monotherapy during percutaneous coronary intervention, with mandatory potent P2Y12 inhibition, routine radial artery access, and only bail-out glycoprotein IIb/IIIa inhibition. Kaplan-Meier event rates were assessed for the primary end point, consisting of a composite of all-cause death, myocardial reinfarction, or major bleeding, within 180 days.. The elderly (n=1592) had more than twice the risk of all events compared with younger patients (n=4406). Baseline and periprocedural characteristics were equal between bivalirudin (n=799) and heparin (n=793) treated patients ≥75 years. No differences were found in the elderly between bivalirudin and heparin monotherapy regarding the primary end point (180-day all-cause death, myocardial reinfarction, or major bleeding), the individual components of the primary end point, definite stent thrombosis, or stroke.. In this prespecified subgroup analysis of the VALIDATE-SWEDEHEART trial, elderly patients with myocardial infarction had a highly increased risk of all events. However, no difference in outcomes could be observed with an anticoagulation strategy with either bivalirudin or heparin as monotherapy in this patient group.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Coronary Thrombosis; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Non-ST Elevated Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Recombinant Proteins; Recurrence; Registries; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Stroke; Sweden; Time Factors; Treatment Outcome

The optimal anti-coagulation strategy for patients with non-ST-elevation myocardial infarction treated with percutaneous coronary intervention is unclear in contemporary clinical practice of radial access and potent P2Y12-inhibitors. The aim of this study was to investigate whether bivalirudin was superior to heparin monotherapy in patients with non-ST-elevation myocardial infarction without routine glycoprotein IIb/IIIa inhibitor use.. In a large pre-specified subgroup of the multicentre, prospective, randomised, registry-based, open-label clinical VALIDATE-SWEDEHEART trial we randomised patients with non-ST-elevation myocardial infarction undergoing percutaneous coronary intervention, treated with ticagrelor or prasugrel, to bivalirudin or heparin monotherapy with no planned use of glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention. The primary endpoint was the rate of a composite of all-cause death, myocardial infarction or major bleeding within 180 days.. Bivalirudin as compared to heparin during percutaneous coronary intervention for non-ST-elevation myocardial infarction did not reduce the composite of all-cause death, myocardial infarction or major bleeding in non-ST-elevation myocardial infarction patients receiving current recommended treatments with modern P2Y12-inhibitors and predominantly radial access.

Topics: Aged; Anticoagulants; Antithrombins; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Recombinant Proteins; Stents; Sweden; Thrombosis; Ticagrelor

Our aim was to study the impact of sex on anticoagulant treatment outcomes during percutaneous coronary intervention in acute myocardial infarction patients.. This study was a prespecified analysis of the Bivalirudin versus Heparin in ST-Segment and Non ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated according to Recommended Therapies Registry Trial (VALIDATE-SWEDEHEART) trial, in which patients with myocardial infarction were randomised to bivalirudin or unfractionated heparin during percutaneous coronary intervention. The primary outcome was the composite of death, myocardial infarction or major bleeding at 180 days.. There was a lower risk of the primary outcome in women assigned to bivalirudin than to unfractionated heparin (13.6% vs 17.1%, hazard ratio 0.78, 95% confidence interval (0.60-1.00)) with no significant difference in men (11.8% vs 11.2%, hazard ratio 1.06 (0.89-1.26),. In women, bivalirudin was associated with a lower risk of adverse outcomes, compared to unfractionated heparin, primarily due to a significant reduction in Bleeding Academic Research Consortium 2 bleeds.

Topics: Acute Disease; Administration, Intravenous; Aged; Anticoagulants; Antithrombins; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Registries; Risk Assessment; Sex Factors; ST Elevation Myocardial Infarction; Sweden

In the Bivalirudin versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated according to Recommended Therapies Registry Trial (VALIDATE-SWEDEHEART), bivalirudin was not superior to unfractionated heparin in patients with acute coronary syndrome undergoing invasive management. We assessed whether the access site had an impact on the primary endpoint of death, myocardial infarction or major bleeding at 180 days and whether it interacted with bivalirudin/unfractionated heparin.. Transradial access was associated with lower risk of death, myocardial infarction or major bleeding at 180 days. Bivalirudin was not associated with less bleeding, irrespective of access site.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Antithrombins; Female; Femoral Artery; Hemorrhage; Heparin; Hirudins; Humans; Male; Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Prospective Studies; Radial Artery; Recombinant Proteins; Registries; ST Elevation Myocardial Infarction; Treatment Outcome

To explore the efficiency and safety of bivalirudin in patients undergoing emergency percutaneous coronary intervention via radial access.. Bivalirudin reduces bleeding risks over heparin in patients undergoing PCI. However, bleeding advantages of bivalirudin in patients undergoing transradial intervention is uncertain.. In the BRIGHT trial, 1,723 patients underwent emergency PCI via radial access, with 576 patients in the bivalirudin arm, 576 in the heparin arm and 571 in the heparin plus tirofiban arm. The primary outcome was 30-day net adverse clinical event (NACE), defined as a composite of major cardiac and cerebral events or any bleeding.. 30-day NACE occurred in 5.7% with bivalirudin, 7.8% with heparin alone (vs. bivalirudin, P = 0.159), and 10.3% with heparin plus tifofiban (vs. bivalirudin, P = 0.004). The 30-day bleeding rate was 0.9% for bivalirudin, 2.3% for heparin (vs. bivalirudin, P = 0.057), and 5.8% for heparin plus tirofiban (vs. bivalirudin, P < 0.001). Major cardiac and cerebral events (4.9 vs. 5.7 vs. 4.6%, P = 0.899), stent thrombosis (0.5 vs. 0.5 vs. 0.7%, P = 0.899) and acquired thrombocytopenia (0.2 vs. 0.5 vs. 0.9%, P = 0.257) at 30 days were similar among three arms. The interaction test for PCI access and randomized treatment showed no significance on all bleeding (P > 0.05).. The bleeding benefit of bivalirudin was independent of artery access. Bivalirudin lead to statistical reduction on bleeding risks in comparison to heparin plus tirofiban, and only small numerical difference in comparison to heparin, with comparable risks of ischemic events and stent thrombosis in patients with acute myocardial infarction (AMI) undergoing emergency transradial PCI. © 2016 Wiley Periodicals, Inc.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Cardiac Catheterization; China; Emergencies; Female; Hemorrhage; Hirudins; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Non-ST Elevated Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Radial Artery; Recombinant Proteins; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Time Factors; Tirofiban; Treatment Outcome; Tyrosine; Warfarin; Young Adult

To evaluate the impact of antithrombotic regimens during the medical phase of treatment among 13,819 patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) treated with an early invasive strategy in the acute catheterization and urgent intervention triage strategy (ACUITY) trial.. Endpoints included composite major adverse cardiac events (MACE), major bleeding, and net adverse clinical events (NACE; MACE or major bleeding). The median (interquartile range) duration of antithrombin use in the medical only treatment phase was 6.5 (1.8-22.5) hours. MACE, major bleeding, and NACE during the medical only phase occurred in 63 (0.5%), 117 (0.9%), and 178 (1.3%) patients, respectively. MACE rates in the medical-treatment-only phase were not significantly different between the four randomized medical regimens used (heparin alone, bivalirudin alone, heparin plus a glycoprotein IIb/IIIa inhibitor [GPI], and bivalirudin plus GPI) (Ptrend  = 0.65). The lowest rates of major bleeding and NACE during the medical treatment phase occurred in patients treated with bivalirudin alone (Ptrend  = 0.0006 and Ptrend  = 0.0004, respectively).. In patients with NSTE-ACS undergoing an early invasive strategy, treatment with bivalirudin alone significantly reduced major bleeding and improved net clinical outcomes during the upstream medical management phase with comparable rates of MACE. © 2015 Wiley Periodicals, Inc.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Antithrombins; Coronary Artery Bypass; Drug Therapy, Combination; Enoxaparin; Female; Hemorrhage; Hirudins; Humans; Male; Middle Aged; Non-ST Elevated Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Recombinant Proteins; Risk Factors; Time Factors; Treatment Outcome

The optimal anticoagulant for patients with acute coronary syndrome treated with percutaneous coronary intervention (PCI) has not been validated in current practice of radial approach and pretreatment with potent P2Y12 inhibitors. Several studies have indicated increased bleeding rate and, in some instances, even increased mortality by the routine use of heparin and glycoprotein IIb/IIIa inhibitors compared to bivalirudin. Direct comparison of bivalirudin versus heparin alone has yielded contradictory results depending on study designs.. The VALIDATE-SWEDEHEART trial is a multicenter, prospective, randomized, registry-based, controlled, and open-label clinical trial in patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI undergoing PCI pretreated with ticagrelor, prasugrel, or cangrelor. We hypothesize that bivalirudin is superior to heparin alone in reducing death, myocardial infarction, and major bleeding events at 180 days (primary end point). The trial will enroll 3,000 patients with STEMI and 3,000 patients with non-STEMI undergoing PCI. The trial will use a hybrid registry-based randomized clinical trial design where inclusion, randomization, and baseline data collection are performed using The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registry. The primary composite end point (death, myocardial infarction, or major bleeding events at 180 days) will be identified through active screening after 7 and 180 days and adjudicated by a blinded central end point committee. Secondary end points and long-term outcomes will be recorded from national registries.. The VALIDATE-SWEDEHEART trial is founded on a nationwide clinical registry and uses a hybrid registry-based randomized clinical trial (RRCT) design methodology to evaluate efficacy and safety of bivalirudin as compared to heparin alone for acute coronary syndrome, in a large population receiving contemporary recommended therapies including predominantly radial invasive approach and pretreatment with potent P2Y12 inhibitors.

Topics: Administration, Intravenous; Aged; Anticoagulants; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Electrocardiography; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Non-ST Elevated Myocardial Infarction; Outcome and Process Assessment, Health Care; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Registries; ST Elevation Myocardial Infarction; Treatment Outcome

There are limited data on bivalirudin monotherapy in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) with positive biomarkers of myocardial necrosis (troponin and/or creatine kinase-myocardial band isoenzyme). We sought to evaluate the safety and efficacy of bivalirudin monotherapy in patients with positive biomarkers from the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial.. We compared the net adverse clinical events [composite ischemia - (death, myocardial infarction, or unplanned ischemic revascularization) - or noncoronary artery bypass graft surgery (CABG)-related major bleeding] among patients with biomarker-positive NSTE-ACS in the ACUITY trial overall and by antithrombotic strategy.. Among 13 819 patients with NSTE-ACS enrolled in ACUITY, 4728 patients presented with positive biomarkers and underwent an early invasive strategy. Of those, 1547 were randomized to heparin plus a glycoprotein IIb/IIIa inhibitor (GPI), 1555 to bivalirudin plus GPI, and 1626 to bivalirudin monotherapy. Compared with biomarker-negative patients, biomarker-positive patients had higher 30-day rates of net adverse clinical events (14.0 vs. 12.4%; P = 0.04), all-cause death (1.3 vs. 0.5%; P = 0.001), cardiac death (1.1 vs. 0.5%; P = 0.005), and non-CABG-related major bleeding (6.5 vs. 5.2%, P = 0.03). At 30 days, bivalirudin monotherapy was associated with significantly less non-CABG-related major bleeding (bivalirudin monotherapy 4.1% vs. bivalirudin plus GPI 8.4% vs. heparin plus GPI 7.1%) with comparable rates of composite ischemia (bivalirudin monotherapy 9.2% vs. bivalirudin plus GPI 9.9% vs. heparin plus GPI 8.4%). In a multivariable model, bivalirudin monotherapy was associated with a significant reduction in non-CABG-related major bleeding but was not associated with an increased risk of death, myocardial infarction, unplanned revascularization or stent thrombosis.. Compared with heparin plus GPI or bivalirudin plus GPI, bivalirudin monotherapy provides similar protection from ischemic events with less major bleeding at 30 days among patients with NSTE-ACS and positive biomarkers.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Antithrombins; Creatine Kinase, MB Form; Enoxaparin; Female; Hirudins; Humans; Male; Middle Aged; Non-ST Elevated Myocardial Infarction; Partial Thromboplastin Time; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Hemorrhage; Randomized Controlled Trials as Topic; Recombinant Proteins; Troponin

Topics: Adrenal Gland Diseases; Aged; Anticoagulants; Atrial Fibrillation; Diabetic Angiopathies; Hemorrhage; Heparin; Hirudins; Humans; Hydrocortisone; Hypotension; Male; Non-ST Elevated Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Thrombocytopenia; Treatment Outcome; Vasoconstrictor Agents

Practice patterns in anticoagulant strategies used during percutaneous coronary intervention (PCI) in the United States for patients with non-ST-segment-elevation myocardial infarction and the comparative outcomes between bivalirudin and unfractionated heparin (UFH) have not been well described.. Trends in anticoagulant use were examined among 553 562 PCIs performed by 9254 operators at 1538 hospitals for non-ST-segment-elevation myocardial infarction from 2009 to 2014 within the CathPCI Registry. To compare bivalirudin with UFH, propensity score matching and instrumental variable (IV) methods with operator preference for bivalirudin as the instrument were used. To determine whether differences in outcomes were because of differences in glycoprotein IIb/IIIa inhibitor (GPI) use, a test of mediation was performed using the IV. Outcomes were in-hospital bleeding and mortality. Bivalirudin use increased from 2009 to 2013 but declined during 2014. GPI use was 50.5% during UFH PCIs and 12.0% during bivalirudin PCIs. Before GPI adjustment, bleeding reductions with bivalirudin ranged from 2.04% (IV: 95% confidence interval [CI]: 1.81%, 2.27%) to 2.29% (propensity score: 95% CI: 2.14%, 2.44%) and mortality reductions ranged from 0.16% (IV: 95% CI: 0.03%, 0.28%) to 0.25% (propensity score: 95% CI: 0.17%, 0.33%). After GPI adjustment in the IV, more than half the bleeding reduction with bivalirudin was because of the lower use of GPIs (risk difference, -0.84%; 95% CI: -1.11%, -0.57%), and no survival benefit was apparent (risk difference, -0.10%; 95% CI: -0.24%, 0.05%). Bleeding reductions with bivalirudin were largest for transfemoral PCI (GPI-adjusted risk difference, -1.11%; 95% CI: -1.43%, -0.80%) and negligible for transradial PCI (GPI-adjusted risk difference, 0.09%; 95% CI: -0.32%, 0.50%).. In the largest comparative analysis of bivalirudin versus UFH for non-ST-segment-elevation myocardial infarction to date, bivalirudin was associated with lower in-hospital bleeding and mortality given current practices with respect to GPI use and access site. Bleeding differences were, in part, explained by the greater use of GPIs with UFH. Reductions in bleeding were largest among those undergoing transfemoral PCI, whereas no bleeding benefit was observed for those treated with transradial PCI.

Topics: Aged; Antithrombins; Blood Loss, Surgical; Female; Hirudins; Hospital Mortality; Humans; Incidence; Inpatients; Male; Middle Aged; Non-ST Elevated Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Postoperative Hemorrhage; Practice Patterns, Physicians'; Recombinant Proteins; Registries; Retrospective Studies; Risk Factors; Treatment Outcome; United States