bivalirudin and Acute-Disease

The aim of this study was to evaluate the efficacy of various doses of post-primary percutaneous coronary intervention (PCI) bivalirudin infusion to prevent acute stent thrombosis (AST).. In several recent randomized controlled trials, bivalirudin infusion was continued post-PCI as either a full PCI dose (Biv-Full) or a reduced dose (Biv-Low) to reduce the risk for AST. The results of these trials varied, so the authors performed a meta-analysis of RCTs to determine whether the risk for AST is dose dependent.. Scientific databases and Web sites were searched for RCTs. A traditional meta-analysis was performed using moderator analyses and network meta-analysis using mixed-treatment comparison models to compare the efficacy of various bivalirudin doses in reducing AST.. Data from 5 trials including 16,294 patients were analyzed. Compared with heparin, bivalirudin increased AST risk 2-fold, but this was ameliorated by continuing Biv-Full (risk ratio: 0.90, 95% confidence interval: 0.32 to 2.54; p = 0.852). This effect was not seen with Biv-Low. Similarly, in mixed-treatment models, no difference in AST rate was found between heparin and Biv-Full (odds ratio: 0.97; 95% confidence interval: 0.36 to 2.21). After 30 days, bivalirudin decreased the risk for major bleeding by 47% compared with heparin; this benefit persisted even with continued Biv-Full post-PCI (risk ratio: 0.29; 95% confidence interval: 0.16 to 0.53; p < 0.001).. Although bivalirudin is associated with a greater risk for AST than heparin post-primary PCI, this limitation may be mitigated by continuing Biv-Full (not Biv-Low) 3 to 4 h post-operatively. The decrease in bleeding risk with bivalirudin compared with heparin is not compromised by this strategy.

Topics: Acute Disease; Anticoagulants; Antithrombins; Coronary Thrombosis; Dose-Response Relationship, Drug; Evidence-Based Medicine; Hemorrhage; Heparin; Hirudins; Humans; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Factors; ST Elevation Myocardial Infarction; Stents; Time Factors; Treatment Outcome

Although bivalirudin has been shown to reduce bleeding events in patients undergoing percutaneous coronary intervention, residual concerns remain about a possible higher risk of early (within 30 days) stent thrombosis (ST). Therefore, we performed a meta-analysis of randomised trials reporting ST events with bivalirudin compared to other antithrombotic therapies (heparins ± glycoprotein IIb/IIIa inhibitors). A systematic literature search of electronic resources was performed through May, 2014. The primary endpoint was definite early ST, according to Academic Research Consortium criteria. Secondary endpoints included: all-cause death, myocardial infarction and major bleeding. A total of 11 trials, including 16,415 patients, were accrued. Compared to other regimens, bivalirudin significantly increased the risk of early ST (odds ratio [OR]=1.80; 95 % confidence interval [CI], 1.28-2.52; p=0.0007) and reduced the risk of major bleeding (OR [95 %CI]=0.64 [0.51-0.82], p=0.0003), with a comparable risk of mortality or myocardial infarction. The higher risk of early ST was mainly attributable to acute (OR [95 % CI] =4.33 [2.33-8.05], p < 0.001) than subacute (OR [95 % CI] =0.89 [0.53-1.50], p =0.67) ST events (p for interaction < 0.001). Non-fatal myocardial infarction was the most common presentation (83 %) of early ST events, while death occurred infrequently (about 5 %). In conclusion, in patients undergoing PCI, bivalirudin compared to heparins is associated with a higher risk of early ST, which is mainly related to more frequent acute events. Further studies are required to evaluate alternative strategies to mitigate this risk, without hampering the benefits derived from the reduction in bleeding events with bivalirudin.

Topics: Acute Disease; Drug Therapy, Combination; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Multicenter Studies as Topic; Myocardial Infarction; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk; Stents; Thrombosis; Treatment Outcome

The anticoagulant properties of heparin were discovered in 1916, and by the 1930s researchers were evaluating its therapeutic use in clinical trials. Treatment of unstable angina with unfractionated heparin (UFH), in addition to aspirin, was introduced into clinical practice in the early 1980s. UFH was combined with aspirin to suppress thrombin propagation and fibrin formation in patients presenting with acute coronary syndromes (ACS) or patients undergoing percutaneous coronary intervention (PCI). However, UFH stimulates platelets, leading to both activation and aggregation, which may further promote clot formation. Clinical trials have demonstrated that newer agents, such as the low-molecular-weight heparins (LMWHs), are superior to UFH for medical management of unstable angina or non-ST-segment elevation myocardial infarction. Increasingly, the LMWHs have been used as the anticoagulant of choice for patients presenting with ACS. For patients undergoing PCI, LMWH provides no sub-stantial benefit over UFH for anticoagulation; however, direct thrombin inhibitors (DTIs) have demonstrated safety and efficacy in this setting. UFH is likely to be replaced by more effective and safer antithrombin agents, such as DTIs. DTIs have antiplatelet effects, anticoagulant action, and most do not bind to plasma proteins, thereby providing a more consistent dose-response effect than UFH. The FDA has approved 4 parenteral DTIs for various indications: lepirudin, argatroban, bivalirudin, and desirudin. The antiplatelet, anticoagulant, and pharmacokinetic properties of bivalirudin support its use as the anticoagulant of choice for both lower- and higher-risk patients, including those undergoing PCI.

Topics: Acute Disease; Angina Pectoris; Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Arginine; Fondaparinux; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Models, Molecular; Molecular Structure; Myocardial Ischemia; Peptide Fragments; Pipecolic Acids; Platelet Activation; Polysaccharides; Recombinant Proteins; Sulfonamides; Syndrome; Thrombin; Thrombosis

The standard of care for patients with acute coronary syndrome is antithrombotic and antiplatelet therapies along with early percutaneous coronary intervention. Because of the limitations of heparin, there has been an interest in direct thrombin inhibitors, such as bivalirudin, which is now the anticoagulant of choice in percutaneous coronary intervention.

Topics: Acute Disease; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Disease; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Thrombosis

Bivalirudin is a member of the direct thrombin inhibitor group of anticoagulants. It has been evaluated as an alternative to unfractionated and low-molecular-weight heparins in the settings of percutaneous coronary intervention (PCI) and acute coronary syndrome (ACS). Results of clinical trials to date suggest bivalirudin is a viable alternative to the use of a heparin combined with a glycoprotein (GP) IIb/IIIa inhibitor in these settings. Thrombin has a central role in coagulation and platelet activation in ACS and during PCI. Its direct inhibition is an attractive target for therapy in these settings. Bivalirudin is a 20 amino acid polypeptide hirudin analog. It displays bivalent and reversible binding to the thrombin molecule, inhibiting its action. Direct inhibition of thrombin with bivalirudin has theoretical pharmacokinetic and pharmacodynamic advantages over the indirect anticoagulants. A reduction in rates of bleeding without loss of anti-thrombotic efficacy has been a consistent finding across multiple clinical trials. There may be economic benefits to the use ofbivalirudin if it permits a lower rate of use of the GP IIb/IIIa inhibitors. This article reviews the pharmacology of bivalirudin and clinical trial evidence to date. There are now data from multiple clinical trials and meta-analyses in the setting of ACS and PCI. Early results from the acute catheterization and urgent intervention strategy (ACUITY) trial are discussed.

Topics: Acute Disease; Angioplasty, Balloon, Coronary; Anticoagulants; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Ischemia; Peptide Fragments; Platelet Aggregation Inhibitors; Recombinant Proteins; Secondary Prevention; Syndrome; Thrombin; Thrombosis

Topics: Acute Disease; Angioplasty, Balloon, Coronary; Anticoagulants; Arginine; Atrial Fibrillation; Azetidines; Benzylamines; Clinical Trials as Topic; Coronary Disease; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Pipecolic Acids; Recombinant Proteins; Sulfonamides; Syndrome; Thrombin; Thromboembolism; Thrombosis; Venous Thrombosis

Topics: Acute Disease; Angioplasty, Balloon, Coronary; Anticoagulants; Clinical Trials as Topic; Coronary Disease; Fibrinolytic Agents; Hemostatics; Heparin; Hirudin Therapy; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Thrombin

Coronary artery thrombosis is usually triggered by platelet-rich thrombus superimposed on a spontaneously or mechanically disrupted atherosclerotic plaque. Thrombin and platelets both play a role in this process. Unfractionated heparin and aspirin have served as cornerstones in the prevention and treatment of intracoronary thrombus, but unfractionated heparin has several limitations that necessitate the use of adjunctive therapies, such as glycoprotein IIb/IIIa receptor inhibitors and clopidogrel, in order to reduce the risk of ischemic events. These combination therapies, however, typically increase the risk for bleeding complications, as well as the cost and complexity of treatment. Bivalirudin (Angiomax, The Medicines Company), a thrombin-specific anticoagulant, does not share heparin's limitations. Bivalirudin appears to provide clinical advantages over unfractionated heparin therapy in acute coronary syndrome patients and those undergoing percutaneous coronary intervention, without increasing cost or complexity of treatment for most patients.

Topics: Acute Disease; Angioplasty, Balloon, Coronary; Anticoagulants; Clinical Trials as Topic; Coronary Disease; Heparin; Hirudins; Humans; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Randomized Controlled Trials as Topic; Recombinant Proteins; Syndrome; Thrombosis

Ximelagatran and bivalirudin are direct thrombin inhibitors that have been studied for the prevention and treatment of thrombosis and have potential advantages over the traditional indirect thrombin inhibitors (i.e., warfarin, unfractionated heparin and low molecular-weight heparin). They are both reversible inhibitors of thrombin and block both circulating and fibrin-bound thrombin. Ximelagatran and bivalirudin possess favourable pharmacokinetic and pharmacodynamic profiles including wider therapeutic indices, faster onsets of action and less interpatient variability compared to indirect thrombin inhibitors. Ximelagatran has shown favourable clinical trial results in venous thromboembolism prophylaxis and atrial fibrillation. Similarly, bivalirudin has shown positive results in patients with acute coronary syndromes, however, further investigation is needed. Ximelagatran and bivalirudin have shown promising results in the management of thrombosis and the results of future studies confirming their use for the aforementioned indications are anticipated.

Topics: Acute Disease; Administration, Oral; Antithrombins; Azetidines; Benzylamines; Clinical Trials, Phase III as Topic; Coronary Disease; Double-Blind Method; Hirudins; Humans; Peptide Fragments; Randomized Controlled Trials as Topic; Recombinant Proteins; Syndrome; Thrombosis

The central role of thrombin in the initiation and propagation of intravascular thrombus provides a strong rationale for direct thrombin inhibitors in acute coronary syndromes (ACS). Direct thrombin inhibitors are theoretically likely to be more effective than indirect thrombin inhibitors, such as unfractionated heparin or low-molecular-weight heparin, because the heparins block only circulating thrombin, whereas direct thrombin inhibitors block both circulating and clot-bound thrombin. Several initial phase 3 trials did not demonstrate a convincing benefit of direct thrombin inhibitors over unfractionated heparin. However, the Direct Thrombin Inhibitor Trialists' Collaboration meta-analysis confirms the superiority of direct thrombin inhibitors, particularly hirudin and bivalirudin, over unfractionated heparin for the prevention of death or myocardial infarction (MI) during treatment in patients with ACS, primarily due to a reduction in MI (odds ratio, 0.80; 95% confidence interval, 0.70 to 0.91) with little impact on death. The absolute risk reduction in the composite of death or MI at the end of treatment (0.8%) was similar at 30 days (0.7%), indicating no loss of benefit after cessation of therapy. Supportive evidence for the superiority of direct thrombin inhibitors over heparin derives from the recently reported Hirulog and Early Reperfusion or Occlusion (HERO)-2 randomized trial with ST-segment elevation ACS, which demonstrated a similar benefit of bivalirudin over heparin for the prevention of death or MI at 30 days (absolute risk reduction 1.0%), again primarily due to a reduction in MI during treatment (odds ratio, 0.70; 95% confidence interval, 0.56 to 0.87), with little impact on death. Further evaluation of hirudin and bivalirudin in the antithrombotic management of patients with ACS is warranted.

Topics: Acute Disease; Angina, Unstable; Antithrombins; Coronary Thrombosis; Fibrinolytic Agents; Forecasting; Heparin; Hirudins; Humans; Meta-Analysis as Topic; Myocardial Infarction; Outcome Assessment, Health Care; Peptide Fragments; Randomized Controlled Trials as Topic; Recombinant Proteins; Thrombin

The chemistry and pharmacology, pharmacokinetics, pharmacodynamics, adverse effects, drug interactions, dosing and administration, and pharmacoeconomics of bivalirudin are reviewed; clinical trials of bivalirudin's application in percutaneous coronary intervention (PCI) are also discussed. Bivalirudin is a direct thrombin inhibitor approved for use in PCI. It reversibly binds to thrombin's catalytic site and substrate recognition site and blocks both circulating and fibrin-bound thrombin. Peak concentrations occur in less than 5 minutes after bolus-dose administration, and its half-life is approximately 25 minutes. It is primarily eliminated renally, and dosage reduction may be required in patients with severe renal dysfunction. Two clinical trials have demonstrated that bivalirudin is at least as effective as unfractionated heparin (UFH) in preventing ischemic complications in PCI. Other trials have shown that bivalirudin has beneficial ischemic and hemorrhagic outcomes in a more modern PCI setting (i.e., intracoronary stent placement, clopidogrel, and glycoprotein IIb/IIIa-receptor inhibitors). Bivalirudin combined with provisional glycoprotein IIb/IIIa inhibitors was noninferior to UFH with planned glycoprotein IIb/IIIa inhibitors and superior to UFH alone with respect to ischemic and hemorrhagic endopoints in PCI. Major bleeding with bivalirudin has occurred in approximately 3% of patients in clinical trials, and it is not known to have any interactions with the cytochrome P-450 isoenzyme system. The acquisition cost of bivalirudin in one study was less than the combination of UFH and glycoprotein IIb/IIIa inhibitors. Bivalirudin combined with provisional glycoprotein IIb/IIIa inhibitors appears to be an acceptable alternative to the standard of care and is superior to UFH alone in PCI.

Topics: Acute Disease; Angioplasty, Balloon, Coronary; Clinical Trials as Topic; Coronary Disease; Drug Interactions; Fibrinolytic Agents; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Thrombin; Thrombosis

Heparin is a commonly used anticoagulant in patients with coronary artery disease but its use does not always result in low rates of ischaemic and bleeding events, so the search for new anticoagulants continues. Thrombin plays a key role in both thrombosis and haemostasis and direct thrombin inhibitors modelled on the hirudin molecule found in the saliva of the medicinal leech, Hirudo medicinalis, have recently been developed. To date, the only direct thrombin inhibitor shown to reduce both the ischaemic and the bleeding complications associated with percutaneous coronary intervention (PCI) is bivalirudin, which is approved for this indication in the US and New Zealand. This agent is currently being studied in patients undergoing PCI with or without glycoprotein IIb/IIIa inhibitors and stenting. Bivalirudin has been shown to significantly reduce the risk of reinfarction in patients with acute myocardial infarction (MI) treated with streptokinase, but its use for this indication is not approved in the US. It may also prove to be beneficial in patients with acute MI treated with other fibrinolytic regimens or with primary or facilitated PCI. Bivalirudin is suitable for use as an alternative to heparin in the majority of patients undergoing PCI and in patients receiving streptokinase for acute MI.

Topics: Acute Disease; Angina Pectoris; Angioplasty, Balloon, Coronary; Anticoagulants; Clinical Trials as Topic; Coronary Artery Disease; Coronary Disease; Coronary Thrombosis; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Recombinant Proteins

Inhibiting thrombin as a key enzyme of the coagulation cascade is therapeutically useful in thromboembolic diseases. In coronary thrombosis, direct thrombin inhibitors promise to be useful for an efficacious therapy. Hirudin and recombinant or synthetic mimetics like hirulog, argatroban and melagatran have proven their efficacy in clinical studies.. Therapy with direct thrombin inhibitors such as hirudin and analogous substances reduces coronary events. Moreover, the agents are useful for therapy of thromboembolic diseases, especially in the case of heparin induced thrombocytopenia type II.

Topics: Acute Disease; Angina, Unstable; Angioplasty, Balloon, Coronary; Animals; Anticoagulants; Antithrombins; Arginine; Azetidines; Benzylamines; Fibrinolytic Agents; Glycine; Hirudin Therapy; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Pipecolic Acids; Platelet Aggregation Inhibitors; Rabbits; Recombinant Proteins; Sulfonamides; Syndrome; Thrombin; Thromboembolism; Thrombosis; Time Factors

Given the central role of thrombin in arterial thrombogenesis, most treatment strategies for acute coronary syndromes are aimed at inhibiting its generation or blocking its activity. Although heparin has been widely used, it has limitations in the setting of arterial thrombosis. These limitations reflect the inability of heparin to inactivate thrombin bound to fibrin, a major stimulus for thrombus growth. In addition, the anticoagulant response to heparin varies from patient to patient, and heparin is neutralized by platelet Factor IV, large quantities of which are released from platelets activated at sites of plaque rupture. Consequently, heparin requires careful laboratory monitoring to ensure an adequate anticoagulant effect. Direct thrombin inhibitors, such as hirudin and bivalirudin, overcome the limitations of heparin. These agents inhibit fibrin-bound thrombin, as well as fluid-phase thrombin, and produce a predictable anticoagulant response. Bivalirudin has both safety and potential efficacy advantages over hirudin. Bivalirudin appears to have a wider therapeutic window than hirudin, possibly because bivalirudin only transiently inhibits the active site of thrombin. The better safety profile of bivalirudin permits administration of higher doses, which may give it an efficacy advantage. Hirudin prevents thrombin from activating protein C, thereby suppressing this natural anticoagulant pathway. In contrast, bivalirudin may promote protein C activation by transiently inhibiting thrombin until it can be bound by thrombomodulin. Differences between bivalirudin and hirudin, as well as other direct thrombin inhibitors, highlight the pitfalls of considering all direct thrombin inhibitors to have equivalent risk-benefit profiles.

Topics: Acute Disease; Antithrombins; Coronary Thrombosis; Drug Monitoring; Fibrinolytic Agents; Heparin; Hirudin Therapy; Hirudins; Humans; Peptide Fragments; Protein C; Recombinant Proteins

Hirulog therapy has been studied extensively in numerous settings including prevention of DVT, treatment of unstable angina, treatment of acute myocardial infarction during thrombolysis, and prevention of acute complications of PTCA. Being one of the first direct thrombin inhibitors in clinical development, it has had to 'test the waters', so to speak, of the relationship between pathophysiology and clinical trial design: what are the correct indications, patient entry criteria, endopoints, frequency and duration of dosing, and so on? Our findings validate a role for thrombin in treating arterial thromboembolism and demonstrate clinical activity and tolerability of Hirulog.

Topics: Acute Disease; Antithrombins; Coronary Disease; Hirudin Therapy; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Syndrome; Thrombophlebitis

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

Bivalirudin has been associated with reduced bleeding and mortality during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI). However, increased rates of acute stent thrombosis (AST) have been noted when bivalirudin is discontinued at the end of the procedure, which is perhaps related to this medication's short half-life.. To evaluate the clinical effect of procedure duration on AST when either bivalirudin or heparin plus glycoprotein IIb/IIIa receptor inhibitor (GPI) is used.. An ad hoc analysis of the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) clinical trial was performed between March 1, 2015, and April 30, 2016, on patients who underwent primary percutaneous coronary intervention with stents and were randomized 1:1 to bivalirudin or heparin plus GPI. Defined as the difference between the patient's arrival at the catheterization laboratory and the patient's final angiogram. Participants included 3602 patients with STEMI, aged 18 years or older, who were undergoing primary percutaneous coronary intervention and presenting less than 12 hours from symptom onset.. Clinical events committee-adjudicated definite AST (occurring ≤24 hours after percutaneous coronary intervention).. Among patients included in this analysis, procedure time was identified in 1286 receiving bivalirudin and 1412 receiving heparin plus GPI. Shorter procedures were defined as the lowest quartile of duration (<45 minutes). Patients undergoing shorter procedures were younger and less likely to be hypertensive and smokers. Shorter procedures were less complicated with fewer stents implanted, less multivessel stenting, less thrombus, and less no-reflow. An increased risk of definite AST was associated with shorter than with longer procedures with bivalirudin (7 [2.1%] vs 7 [0.7%]; relative risk, 2.87; 95% CI, 1.01-8.17; P = .04) but not with heparin plus GPI (0 vs 3 [0.3%]; P = .30).. Despite less procedural complexity, shorter primary percutaneous coronary intervention time was associated with an increased risk of AST in patients treated with bivalirudin but not patients treated with heparin plus GPI, possibly because of the rapid offset of bivalirudin's antithrombotic effect during a window of limited oral antiplatelet action.. clinicaltrials.gov Identifier: NCT00433966.

Topics: Acute Disease; Aged; Anticoagulants; Antithrombins; Drug Therapy, Combination; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Operative Time; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Recombinant Proteins; Risk Factors; ST Elevation Myocardial Infarction; Stents; Thrombosis

Reinfarction after primary percutaneous coronary intervention in patients with ST-segment-elevation myocardial infarction has negative consequences. Little is known about reinfarction after drug-eluting stents and bivalirudin anticoagulation. We, therefore, sought to determine the incidence, predictors, and implications of reinfarction after primary percutaneous coronary intervention in the contemporary era.. Outcomes were assessed in 3202 patients undergoing stent implantation for ST-segment-elevation myocardial infarction in the Harmonizing Outcomes with RevascularIZatiON and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial. Independent predictors of reinfarction and mortality were identified by Cox proportional hazards modeling. The cumulative incidence of reinfarction was 1.8% at 30 days, 4.0% at 1 year, and 6.9% at 3 years. Definite stent thrombosis was responsible for 76.3% of reinfarctions occurring within 30 days and 52.0% of all reinfarctions within 3 years. Independent predictors of reinfarction were current smoking, Killip class ≥2, baseline thrombocytosis, multivessel disease, symptom onset-to-balloon time, and total stent length. Randomization to bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor and use of drug-eluting versus bare metal stents were not significant predictors of reinfarction. Reinfarction was a powerful independent predictor of subsequent cardiac mortality (hazard ratio [95% confidence interval]=7.65 [4.47-13.09]; P<0.0001) and all-cause mortality (hazard ratio [95% confidence interval]=2.88 [1.74-4.78]; P<0.0001).. Despite advances in pharmacotherapy and stents, reinfarction after primary percutaneous coronary intervention is not infrequent, in the contemporary era is most often attributable to stent thrombosis, and is strongly associated with subsequent cardiac and all-cause mortality. Further enhancements in drugs and devices to prevent reinfarction are needed to improve outcomes in high-risk patients with ST-segment-elevation myocardial infarction.. http://www.clinicaltrials.gov. Unique identifier: NCT00433966.

Topics: Acute Disease; Aged; Antithrombins; Drug-Eluting Stents; Electrocardiography; Female; Follow-Up Studies; Heparin; Hirudins; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Prospective Studies; Recombinant Proteins; Recurrence; Risk Factors; Survival Analysis; Thrombosis; Treatment Outcome

Although the reduction in mortality with bivalirudin compared with unfractionated heparin plus glycoprotein IIb/IIIa inhibitors in the Harmonizing Outcome with Revascularization and Stent in Acute Myocardial Infarction (HORIZONS-AMI) trial has been attributed to lower rates of major bleeding, alternative mechanisms have not been investigated in depth. We sought to investigate whether there might be an interaction between white blood cell (WBC) count and bivalirudin for the risk of mortality, and whether this interaction is independent of major bleeding.. Among the 3602 patients enrolled in the HORIZONS-AMI trial, WBC count was available in 3433 (95.3%) patients. Patients were stratified according to WBC tertiles. At 1-year follow-up, bivalirudin was associated with significantly lower rates of mortality and cardiac mortality compared with unfractionated heparin plus glycoprotein IIb/IIIa inhibitors in patients in the upper WBC tertile (all-cause death: 4.1% versus 9.3%, respectively; P=0.0004; cardiac death: 2.0% versus 6.9%; respectively; P<0.0001) but not in patients in the mid-WBC or lower WBC tertiles. The reduction of mortality with bivalirudin across WBC tertiles was independent of major bleeding, and a significant interaction was apparent for 1-year all-cause mortality and cardiac mortality between WBC and bivalirudin therapy. Similar findings were apparent at 3 years.. In patients with ST-segment-elevation myocardial infarction, a significant interaction between bivalirudin therapy and admission WBC count was apparent for 1-year mortality. The reduction in mortality was independent of major bleeding, suggesting that other mechanisms may be implicated in the survival benefit observed with bivalirudin.. http://www.clinicaltrials.gov. Unique identifier: NCT00433966.

Topics: Acute Disease; Aged; Electrocardiography; Female; Follow-Up Studies; Hemorrhage; Heparin; Hirudins; Humans; Integrin beta3; Leukocyte Count; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Platelet Membrane Glycoprotein IIb; Prospective Studies; Recombinant Proteins; Survival Analysis

We sought to evaluate clinical outcomes of patients with diabetes mellitus in the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial, overall and by treatment arm.. In the ACUITY trial, 13,819 patients with moderate- or high-risk acute coronary syndromes (ACS) were randomized to heparin (unfractionated or enoxaparin) plus glycoprotein IIb/IIIa inhibition (GPI), bivalirudin plus GPI, or bivalirudin monotherapy. Compared with heparin plus GPI, bivalirudin monotherapy resulted in similar protection from ischemic events with less major bleeding. Whether these results apply to patients with diabetes is unknown.. We evaluated the impact of diabetes on 30-day net adverse clinical outcomes (composite ischemia [death, myocardial infarction, or unplanned ischemic revascularization] or major bleeding), overall and by antithrombotic strategy.. Diabetes was present in 3,852 randomized patients (27.9%). Compared with nondiabetic patients, diabetic patients had higher 30-day rates of net adverse clinical outcomes (12.9% vs. 10.6%; p < 0.001), composite ischemia (8.7% vs. 7.2%; p = 0.003), and major bleeding (5.7% vs. 4.2%; p < 0.001). Among diabetic patients, compared with heparin plus GPI, bivalirudin plus GPI resulted in similar rates of net adverse clinical outcomes (14.0% vs. 13.8%; p = 0.89), while bivalirudin monotherapy resulted in a similar rate of composite ischemia (7.9% vs. 8.9%; p = 0.39) and less major bleeding (3.7% vs. 7.1%; p < 0.001), yielding fewer net adverse clinical outcomes (10.9% vs. 13.8%; p = 0.02).. Diabetic patients with ACS managed invasively have higher rates of composite ischemia and major bleeding. Compared with treatment with heparin plus GPI, bivalirudin monotherapy provides similar protection from ischemic events with less major bleeding, resulting in a significant reduction in net adverse clinical outcomes.

Topics: Acute Coronary Syndrome; Acute Disease; Adult; Aged; Aged, 80 and over; Anticoagulants; Cardiac Catheterization; Diabetes Complications; Enoxaparin; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Risk Factors; Treatment Outcome

The coronary artery bypass grafting (CABG) heparin-induced thrombocytopenia thrombosis syndrome (HITTS) on- and off-pump safety and efficacy (CHOOSE-ON) trial was designed as a safety and efficacy trial of bivalirudin for use in anticoagulation during cardiopulmonary bypass (CPB) in patients with confirmed or suspected HIT and (or) antiplatelet factor 4/heparin (anti-PF4/H) antibodies.. In an open-label, multicenter trial, 50 patients were enrolled prospectively. The primary study endpoint was in-hospital acute procedural success, defined as the absence of death, Q-wave myocardial infarction (MI), repeat operation for coronary revascularization, and stroke at day seven after surgery or hospital discharge, whichever occurred first. The secondary study endpoints were procedural success, defined as the absence of death, Q-wave MI, repeat operation for coronary revascularization, and stroke, at 30 days and 12 weeks after surgery. Perioperative blood loss, transfusions, and the incidence of major bleeding events were also captured.. There were 49 patients treated with bivalirudin of which 43 had acute HIT and thrombosis syndrome (HITTS) with antibodies at time of surgery. Procedural success in-hospital or at 7 days was achieved in 46 (94%) patients. At day 30 procedural success was achieved in 42 (86%) patients, and after 12 weeks in 40 (82%) patients. Mean intraoperative blood loss was 575 +/- 524 mL, and mean 24-hour postoperative blood loss was 998 +/- 595 mL. Forty-one (84%) patients received transfusions before day 7 or discharge with a mean of 5.6 +/- 3.8 units of red blood cells, 8.6 +/- 7.2 units of platelets, and 6.0 +/- 4.7 units of fresh frozen plasma. No differences in outcome among bivalirudin-treated patients were observed between those in the overall group and those with moderately impaired renal function (n = 10).. The current investigation expands the experience of safe and effective anticoagulation with bivalirudin during CPB to patients with confirmed or suspected HIT and anti-PF4/H antibodies, including in the setting of impaired renal function.

Topics: Acute Disease; Aged; Aged, 80 and over; Antibodies; Anticoagulants; Blood Loss, Surgical; Cardiopulmonary Bypass; Erythrocyte Transfusion; Female; Heparin; Hirudins; Humans; Intraoperative Care; Male; Middle Aged; Peptide Fragments; Recombinant Proteins; Syndrome; Thrombocytopenia; Thrombosis; Time Factors; Treatment Outcome

The goal of this study was to evaluate glycoprotein IIb/IIIa inhibition with eptifibatide when administered with indirect thrombin inhibition as compared with monotherapy with direct thrombin inhibition with bivalirudin among patients with non-ST-segment elevation acute coronary syndromes (ACS).. The optimal combination of antiplatelet and antithrombin regimens that maximizes efficacy and minimizes bleeding among patients with non-ST-segment elevation ACS undergoing percutaneous coronary intervention (PCI) is unclear.. A total of 857 patients with non-ST-segment elevation ACS were assigned randomly to eptifibatide + reduced dose unfractionated heparin (n = 298), eptifibatide + reduced-dose enoxaparin (n = 275), or bivalirudin monotherapy (n = 284).. Among angiographically evaluable patients (n = 754), the primary end point of post-PCI coronary flow reserve was significantly greater with bivalirudin (1.43 vs. 1.33 for pooled eptifibatide arms, p = 0.036). Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade more often was normal with eptifibatide treatment compared with bivalirudin (57.9% vs. 50.9%, p = 0.048). The duration of ischemia on continuous Holter monitoring after PCI was significantly longer among patients treated with bivalirudin (169 vs. 36 min, p = 0.013). There was no excess of TIMI major bleeding among patients treated with eptifibatide compared with bivalirudin (0.7%, n = 4 vs. 0%, p = NS), but TIMI minor bleeding was increased (2.5% vs. 0.4%, p = 0.027) as was transfusion (4.4% to 0.4%, p < 0.001).. Among moderate- to high-risk patients with ACS undergoing PCI, coronary flow reserve was greater with bivalirudin than eptifibatide. Eptifibatide improved myocardial perfusion and reduced the duration of post-PCI ischemia but was associated with higher minor bleeding and transfusion rates. Ischemic events and biomarkers for myonecrosis, inflammation, and thrombin generation did not differ between agents.

Topics: Acute Disease; Angina, Unstable; Angioplasty, Balloon, Coronary; Antithrombins; Drug Therapy, Combination; Enoxaparin; Eptifibatide; Female; Fibrinolytic Agents; Heparin; Hirudins; Humans; Inflammation; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Peptide Fragments; Peptides; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Postoperative Hemorrhage; Recombinant Proteins; Syndrome

Enoxaparin is an established therapy for the treatment of patients with acute coronary syndrome (ACS), and bivalirudin is commonly used as the antithrombotic agent during percutaneous coronary intervention (PCI). This study was designed to examine the safety of switching from enoxaparin to bivalirudin in these patients.. The Switching from Enoxaparin to Bivalirudin in Patients with Acute Coronary Syndromes without ST-segment Elevation Undergoing Percutaneous Coronary Intervention (SWITCH) trial was a prospective, open-label, multicenter study including 91 patients who presented with an ACS without ST-segment elevation, and who had received greater than or equal to 1 dose of enoxaparin (1 mg/kg SC) within the 12 hours prior to PCI. Patients were enrolled into 3 time categories: Group 1: 0-4; Group 2: 4-8; and Group 3: 8-12 hours from last enoxaparin dose to PCI. The primary endpoint of the study was major bleeding complications.. Baseline characteristics and average number of enoxaparin injections prior to PCI were similar in all 91 patients and among the groups. There was no occurrence of death, Q-wave myocardial infarction (MI), or acute revascularization in any group and no incidence of intracranial or retroperitoneal bleeding. The overall rate of major bleeding (7.7%) was comparable among groups (p = 0.39), as was the incidence of periprocedural non-Q-wave MI (overall 12%; p = 0.58), irrespective of the time interval between enoxaparin and bivalirudin administration.. Switching from enoxaparin to bivalirudin for patients with ACS undergoing PCI appears to be clinically safe without increased risk of major bleeding complications, regardless of the time of enoxaparin administration, and is safe enough to warrant testing it in larger numbers.

Topics: Acute Disease; Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Disease; Enoxaparin; Female; Hemorrhage; Hirudins; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Retreatment; Risk Assessment; Syndrome

The presence of Q waves at presentation with a first acute myocardial infarction reflects a more advanced stage of the infarction process. When infarct-related artery patency (Thrombolysis in Myocardial Infarction 2 or 3 flow) is restored, resolution of ST segment elevation indicating successful myocyte reperfusion may differ according to how far the infarction process has progressed.. In 144 patients with a first acute myocardial infarction treated with streptokinase in the first Hirulog Early Reperfusion Occlusion trial, information was obtained from continuous ST segment monitoring, the presenting electrocardiogram and early angiography performed at a median time of 99 min after the commencement of streptokinase (interquartile range 89-108 min). We determined how many patients had 50% ST recovery within 120 min and in how many cases it was sustained over 4h. In the 109 patients with patent infarct-related arteries, 50% ST recovery occurred in 95% of patients without vs 80% of those with initial Q waves (P=0.03), and sustained ST recovery occurred in 67% of patients without vs 47% of those with initial Q waves (P=0.03). On multivariate analysis including the time from symptom onset to streptokinase therapy, the presence of Q waves at presentation was the only predictor of failure to achieve 50% ST recovery (odds ratio 5.08, 95% confidence interval 1.29-20.01, P=0.02). TIMI 2 flow, as opposed to TIMI 3 flow, was the only predictor of failure to achieve stable ST recovery (odds ratio 2.63, 95% confidence interval 1.15-5.88,P =0.02).. The presence of initial Q waves predicts slower and less complete ST recovery, reflecting reduced myocyte reperfusion, even in those with early infarct artery patency. These patients may be targeted for new therapeutic strategies to improve microvascular reperfusion.

Topics: Acute Disease; Anticoagulants; Aspirin; Coronary Angiography; Coronary Circulation; Double-Blind Method; Electrocardiography; Endpoint Determination; Female; Fibrinolytic Agents; Heparin; Hirudins; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Myocardial Reperfusion; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Recombinant Proteins; Streptokinase; Thrombolytic Therapy; Vascular Patency

Acute myocardial infarction (AMI) occurs when atherosclerotic lesions which present in the coronary arteries cause the intravascular plate to rupture and with the result of myocardial ischemia, hypoxia, and infarct. The preferred treatment for AMI is currently percutaneous coronary intervention (PCI), for which the key to the success is the choice of anticoagulant and thrombolytic drugs during surgery. Here, we aim to explore the effects of atorvastatin combined with bivalirudin on coagulation function, cardiac function, and inflammatory factors in elderly patients with AMI who underwent PCI.. The clinical data of 86 AMI patients who were admitted to our hospital between February 2016 and May 2018 were retrospectively analyzed. Based on different treatments, the patients were divided into the control group and the observation group, with 43 patients in each group. The control group patients were treated with bivalirudin, and the observation group was treated with bivalirudin plus atorvastatin. Both groups of patients underwent PCI and the clinical efficacy, coagulation function, cardiac function, inflammatory factor levels and cardiovascular events (MACE), and other clinical data were compared between the groups.. The total clinical effective rate in the observation group was significantly higher than that in the control group (90.90% vs. 72.09%) (P<0.05). Fibrinogen (Fg) and D-dimer (D-D) levels were significantly decreased after treatment in both groups but were significantly lower in the observation group than in the control group. The prothrombin time (PT) was significantly prolonged after treatment in both groups but was significantly longer in the observation group than in the control group after treatment (P<0.05). Meanwhile, the left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) were significantly reduced after treatment in both groups but were significantly lower in the observation group than in the control group, whereas the left ventricular ejection fraction (LVEF) was significantly higher in the observation group compared with the control group after treatment (P<0.05). After treatment, serum levels of transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), and IL-6 were significantly reduced in both groups but the levels were significantly lower in the observation group than in the control group (P<0.05). The overall incidence of MACE in the observation group was significantly lower than that in the control group (9.30% vs. 30.23%) (P<0.05).. Atorvastatin combined with bivalirudin can improve the efficiency of clinical treatment in elderly AMI patients who undergo PCI, while simultaneously improving blood coagulation function and reducing the occurrence of bleeding, compared with bivalrudin alone. It can also decrease the level of inflammatory factors, promote vascular recanalization, and improve myocardial ischemia, thereby reducing the incidence of MACE and improving patient prognosis.

Topics: Acute Disease; Aged; Atorvastatin; Blood Coagulation; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Retrospective Studies; Stroke Volume; Treatment Outcome; Ventricular Function, Left

Acute heparin-induced thrombocytopenia (HIT) patients present a myriad of anticoagulation management challenges, in clinical settings where unfractionated heparin (UFH) is the traditional drug of choice. UFH use in cardiac surgery is a known entity that has been subject to rigorous research. Research has, thus, led to its unparalleled use and the development of well-established protocols for cardiac surgery. In comparison to UFH, bivalirudin use for acute HIT patients requiring urgent cardiac surgery with cardiopulmonary bypass (CPB) is still in its infancy. We describe the tailored post-CPB management of refractory bleeding in a 65-year-old infective endocarditis, acute HIT patient with renal failure who underwent urgent aortic valve replacement and mitral valve repair with bivalirudin anticoagulation. A management approach that entailed a combination of continuous venovenous haemofiltration (CVVH), 4-Factor prothrombin complex concentrate (PCC) (Beriplex), recombinant factor VIIa (rFactor VIIa) and desmopressin (DDAVP) were consecutively used post-operatively in theatre. Based on this case study experience, two modifications to institutional protocols are recommended. The first is the use of CVVH in theatre to eliminate bivalirudin in renal failure patients or in patients where bivalirudin elimination is prolonged. Secondly, a 'rescue therapy/intervention' algorithm for the swift identification of refractory bleeding post-CPB is also recommended. Rescue therapy agents, such as a 4-Factor PCCs and rFactor VIIa, should be incorporated into the protocol after a robust evidence-based search and agreement with the haematologist. The aim of these recommendations is to reduce the risk of bleeding associated with bivalirudin use for inexperienced institutions and experienced institutions alike, until larger randomized, controlled studies provide more in-depth knowledge to expand our clinical practice.

Topics: Acute Disease; Aged; Anticoagulants; Aortic Valve; Blood Coagulation Factors; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Deamino Arginine Vasopressin; Factor VIIa; Hemorrhage; Hemostatics; Heparin; Hirudins; Humans; Male; Mitral Valve; Peptide Fragments; Recombinant Proteins; Renal Insufficiency; Thrombocytopenia

A 74-year-old female had urgent surgery with replacement of the ascending aorta for acute type A dissection. Postprocedure, the electrocardiogram showed an ST-segment elevation myocardial infarction in the antero-lateral leads. Angiography revealed a thrombotic occlusion of the left anterior descending artery, treated successfully with bivalirudin administration, thrombus aspiration and a balloon angioplasty. This case involves the rare coexistence of acute type A aortic dissection and myocardial infarction due to coronary plaque thrombosis.

Topics: Acute Disease; Aged; Angioplasty, Balloon, Coronary; Aorta; Aortic Aneurysm; Aortic Dissection; Coronary Angiography; Coronary Vessels; Electrocardiography; Female; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Thrombectomy; Thrombosis; Treatment Outcome

Topics: Acute Disease; Aged; Antithrombins; Clopidogrel; Coronary Thrombosis; Drug-Eluting Stents; Eptifibatide; Female; Fibrinolytic Agents; Heparin; Hirudins; Humans; Peptide Fragments; Peptides; Platelet Aggregation Inhibitors; Recombinant Proteins; Risk Factors; Ticlopidine; Tomography, Optical Coherence

Successful management of acute cardiac tamponade secondary to coronary artery perforation during percutaneous coronary intervention (PCI) includes sealing off the site of perforation and pericardiocentesis. We report two cases of acute cardiac tamponade during PCI associated with the administration of bivalirudin, in which attempts at percutaneous pericardiocentesis failed, due to the present of thrombus, rather blood, in the pericardium.

Topics: Acute Disease; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Cardiac Tamponade; Coronary Artery Disease; Coronary Vessels; Female; Heart Injuries; Hemostatic Techniques; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Pericardiectomy; Pericardiocentesis; Recombinant Proteins; Stents; Sternotomy; Thrombosis; Treatment Failure; Ultrasonography; Wounds, Penetrating

Heparin-induced thrombocytopenia (HIT) is a serious, antibody-mediated complication of heparin which significantly confers risks of thrombosis and devastating outcomes. Once diagnosed, it requires immediate cessation of heparin and therapy with an alternative anticoagulant. No data are available in the literature on the pathophysiology and clinical implications of performing prolonged extracorporeal membrane oxygenation with a heparin-coated system in a patient with acute HIT treated with bivalirudin.

Topics: Acute Disease; Aged; Antibodies; Anticoagulants; Extracorporeal Membrane Oxygenation; Female; Heparin; Hirudins; Humans; Mitral Valve Insufficiency; Peptide Fragments; Platelet Count; Recombinant Proteins; Thrombocytopenia

Multiple antithrombotic options are available for patients undergoing primary percutaneous coronary interventions for stent thrombosis elevation acute myocardial infarction. Current utilization and outcomes of antithrombotic agents for primary percutaneous coronary intervention, including bivalirudin, have not been defined.. A total of 84 471 patients were reported from 439 hospitals to the National Registry of Myocardial Infarction-5 registry between April 2004 and June 2005. Consecutive patients undergoing primary percutaneous coronary interventions for stent thrombosis elevation acute myocardial infarction (n=7629 at 231 United States percutaneous coronary intervention capable hospitals) comprised the population analyzed. We examined antithrombotic strategies and the occurrence of adverse cardiac events stratified according to the use of bivalirudin. Logistic regression was performed to control for differences between three antithrombotic therapy treatment groups.. Glycoprotein IIbIIIa inhibitors were used nearly ubiquitously, but given prior to percutaneous coronary interventions in only 36% of patients. Less than one-quarter of patients received clopidogrel prior to percutaneous coronary interventions. Bivalirudin was used in 4.2% of patients (n=320) undergoing primary percutaneous coronary intervention during this time period. Patients treated with bivalirudin were more likely to be elderly (P=0.03), have a history of prior bleeding (P=0.003) and stroke (P=0.06). Major adverse events and bleeding complications were similar in antithrombotic therapy groups (bleeding: bivalirudin 7.8% versus nonbivalirudin 7.5%, P=0.85). The adjusted outcomes were also similar after confining the analysis to bivalirudin patients who had not received any glycoprotein IIbIIIa inhibitors (n=143).. Contemporary primary percutaneous coronary intervention includes mainly clopidogrel and eptifibatide initiated at the time of percutaneous coronary intervention. Patients who received bivalirudin were at higher risk and had similar adjusted outcomes as patients in the nonbivalirudin group. Optimization of primary percutaneous coronary intervention pharmacology requires future randomized clinical trials, examining the timing and type of adjunctive antithrombotic agents.

Topics: Acute Disease; Algorithms; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Thrombosis; Drug Utilization; Female; Hirudins; Humans; Incidence; Logistic Models; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Recombinant Proteins; Registries; Risk Assessment; Stents; Treatment Outcome; United States

To describe data and insights from a national quality improvement initiative known as Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines (CRUSADE), for managing non-ST-segment elevation acute coronary syndrome (ACS), as well as the findings and implications of Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY), a study of bivalirudin with or without a glycoprotein (GP) IIb/IIIa inhibitor in patients with non-ST-segment elevation ACS who were undergoing an invasive intervention, and the results of two recent studies of clopidogrel in patients with ST-segment elevation myocardial infarction (MI) that are not reflected in current ACC/AHA guidelines for managing ST-segment elevation MI.. Data from the CRUSADE registry suggest that there is room for improvement in the use of GP IIb/IIIa inhibitors and clopidogrel during the first 24 hours of hospitalization in patients with non-ST-segment elevation ACS who undergo early invasive cardiac procedures, and in the prescribing of angiotensin converting-enzyme (ACE) inhibitors at the time of discharge. Adherence to ACC/AHA guidelines for non-ST-segment elevation ACS has improved over time but further improvement is needed. Failure to reduce the dose of a GP IIb/IIIa for patients with renal insufficiency resulting in excessive dosing of GP IIb/IIIa inhibitors increases the risk of major bleeding and is particularly common among the elderly, women, and patients with renal insufficiency. The ACUITY study suggests that bivalirudin plus a GP IIb/IIIa inhibitor is a suitable alternative to standard therapy for moderate- to high-risk patients with non-ST-segment elevation ACS who are undergoing early invasive intervention, and bivalirudin alone may be preferred because of a lower risk of major bleeding. However, interpretation of the ACUITY results is complicated by numerous methodologic concerns, so the role of bivalirudin in managing non-ST-segment elevation ACS is still evolving. In patients with ST-segment elevation, clopidogrel provides an early benefit in reopening occluded coronary arteries and a late benefit in reducing cardiovascular mortality and morbidity without increasing the risk of bleeding. Clopidogrel treatment is warranted before as well as after percutaneous coronary intervention in patients with ST-segment elevation MI who receive fibrinolytic therapy. Adding clopidogrel to fibrinolytic therapy and other standard therapy reduces mortality without increasing the risk of bleeding.. Evidence-based guidelines provide recommendations for the management of ACS, but the pace of clinical research is rapid and current guidelines do not reflect the latest research findings. Pharmacists need to stay abreast of new developments and ensure that clinical practice reflects these developments.

Topics: Acute Disease; Angioplasty, Balloon, Coronary; Clinical Protocols; Clopidogrel; Coronary Disease; Drug Administration Schedule; Drug Therapy, Combination; Evidence-Based Medicine; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Outcome Assessment, Health Care; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Practice Guidelines as Topic; Recombinant Proteins; Ticlopidine

Heparin with adjunctive glycoprotein IIb/IIIa platelet receptor (GP IIb/IIIa) inhibitors has demonstrated its effectiveness in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Bivalirudin, a direct thrombin inhibitor, has recently been shown to be an effective alternative for patients undergoing elective PCI.. To assess the angiographic and clinical outcomes of adjunctive pharmacological strategies in a high-risk population presenting with ACS.. Of 891 consecutive PCI patients with ACS, 304 received bivalirudin (60.5% male, 68+/-11 years) and were compared with 283 who received heparin (58.7% male, 66+/-12 years). A 30-day major adverse cardiac event was defined as the occurrence of cardiac death, nonfatal myocardial infarction, urgent revascularization or major hemorrhage.. Adjunctive GP IIb/IIIa inhibitors were used in 14.1% of the bivalirudin group and in 72.4% of the heparin group (P<0.010). The occurrence of Thrombolysis In Myocardial Infarction (TIMI) flow less than grade 3 was lower and the achievement of angiographic success was higher in the bivalirudin group than in the heparin group (5.2% versus 8.2%, 94.7% versus 89.7%, P=0.039 and P<0.010, respectively). There was no difference between groups in the incidence of bleeding events (bivalirudin 2.0% versus heparin 3.5%, P not significant) and in 30-day major adverse cardiac events (bivalirudin 8.3% versus heparin 5.7%, P=0.223).. In the high-risk cohort undergoing PCI, bivalirudin with provisional GP IIb/IIIa inhibitors achieved better angiographic results. Although not powered to show a difference, and while acknowledging that a selection bias could have affected the data, the present study showed that bivalirudin may be as clinically effective and safe as heparin with adjunctive GP IIb/IIIa inhibitors.

Topics: Acute Disease; Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Angiography; Coronary Disease; Drug Therapy, Combination; Female; Follow-Up Studies; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Risk Factors; Syndrome; Treatment Outcome

Topics: Acute Disease; Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Arthroplasty, Replacement, Knee; Cardiac Catheterization; Drug Delivery Systems; Hirudins; Humans; Male; Myocardial Infarction; Peptide Fragments; Postoperative Care; Recombinant Proteins; Stents

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

Intra-arterial thrombolysis has been demonstrated to improve recanalization and outcomes among patients with acute ischemic stroke. However, thrombolytic agents have limited effectiveness and are associated with a significant risk of bleeding. Bivalirudin is a direct thrombin inhibitor that has been demonstrated in the cardiology literature to have a more favorable efficacy and bleeding profile than other antithrombotic medications. We report the use of bivalirudin during endovascular treatment of acute stroke, when hemorrhagic complications are not uncommon.. A 71-year-old woman with atrial fibrillation presented with right hemiparesis and aphasia and was found to have a National Institutes of Health Stroke Scale score of 10. Computed tomographic scans revealed no evidence of intracranial hemorrhage, aneurysm, or ischemic stroke. Cerebral angiography revealed thromboembolic occlusion of the superior division of the left middle cerebral artery.. For anticoagulation, a loading dose of bivalirudin was intravenously administered before the interventional procedure, followed by continuous infusion. Attempts to remove the clot with an endovascular snare failed to induce recanalization of the vessel. Bivalirudin was then administered intra-arterially. Immediate postprocedural angiography demonstrated restoration of flow in the left middle cerebral artery. Repeat computed tomographic scans demonstrated no intracranial hemorrhage. The patient's hemiparesis and aphasia were nearly resolved and her National Institutes of Health Stroke Scale score was 2 at the time of her discharge 5 days later.. To our knowledge, this is the first report of the use of bivalirudin for treatment of acute ischemic stroke. Bivalirudin may be a useful agent for intravenous anticoagulation and intra-arterial thrombolysis in this setting.

Topics: Acute Disease; Aged; Angioplasty; Anticoagulants; Brain Ischemia; Female; Hirudins; Humans; Infusions, Intra-Arterial; Peptide Fragments; Recombinant Proteins; Stroke

We describe two cases of intracoronary vascular brachytherapy where bivalirudin (Angiomax), employed as an anticoagulant, led to abrupt vessel closure or threatened abrupt closure. Use of bivalirudin (Angiomax) during intracoronary brachytherapy may predispose to the formation of intracoronary thrombus, related to the reversible binding kinetics of the bivalirudin to thrombin, and resulting in recovery of thrombin functional activity during periods of prolonged stasis that occur during intracoronary brachytherapy. Intracoronary abciximab administration may be a useful strategy in resolving the acute closure, since abciximab administered early during the formation of thrombus has been shown to facilitate clot lysis.

Topics: Abciximab; Acute Disease; Aged; Antibodies, Monoclonal; Brachytherapy; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Female; Hirudin Therapy; Hirudins; Humans; Immunoglobulin Fab Fragments; Injections; Male; Middle Aged; Peptide Fragments; Recombinant Proteins; Thrombin; Treatment Outcome

Antithrombotic therapy has become the cornerstone of the treatment for atherosclerotic cardiovascular disease. Unfractionated heparin (UFH) has been the thrombin inhibitor of choice for decades. UFH, however, has its deficiencies. To overcome these problems several direct thrombin inhibitors (DTIs) have been developed. These agents are capable of inactivating clot-bound thrombin more efficiently, and provide more predictable and safer anticoagulation in patients with of acute coronary syndromes (ACS). The initial studies of hirudin and bivalirudin in the clinical settings of acute myocardial infarction (AMI), unstable angina (UA) and percutaneous coronary interventions (PCI) conducted in the early 1990s proved to be disappointing. As the knowledge of more appropriate use of these drugs progressed, there is a renewed interest in DTIs. Herein we will review the clinical studies assessing hirudin, bivalirudin and argatroban in the settings of AMI, UA and PCI.

Topics: Acute Disease; Arginine; Coronary Disease; Fibrinolytic Agents; Hirudin Therapy; Hirudins; Humans; Peptide Fragments; Pipecolic Acids; Recombinant Proteins; Sulfonamides; Thrombin