bivalirudin and Coronary-Artery-Disease

We sought to evaluate the efficacy and safety of bivalirudin versus heparin in patients with coronary artery disease undergoing transradial artery coronary intervention (TRI).. Bivalirudin and radial artery access are independently associated with improved cardiovascular outcomes. However, data supporting a strategy of combining both to achieve additive improvements in cardiovascular outcomes provide conflicting results.. A systematic search was performed to identify randomized controlled trials (RCTs) of bivalirudin, in which vascular access sites were reported. The primary outcome was net adverse clinical events (NACE) at 30 days. Secondary outcomes were long-term NACE, short-, and long-term major adverse cardiovascular events, all-cause mortality, myocardial infarction, unplanned revascularization, stent thrombosis, and major bleeding.. Among patients undergoing TRI, use of bivalirudin was associated with significantly reduced 30-day NACE compared with heparin. There was no significant difference in long term NACE, ischemic, or bleeding events compared with heparin.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Catheterization, Peripheral; Coronary Artery Disease; Coronary Thrombosis; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Punctures; Radial Artery; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

The aim of this study was to explore the safety and efficacy of bivalirudin in elderly patients undergoing percutaneous coronary intervention (PCI).. An electronic search was conducted for randomized controlled trials with outcomes of interest in the elderly (≥ 65 years of age). Pooled risk ratios (RR) and 95% confidence interval (CI) using random effects Der Simonian-Laird models were calculated. Primary outcomes were net adverse clinical events (NACE) and major bleeding events at 30 days. Secondary outcomes were major adverse cardiac events (MACE) at 30 days. MACE, all-cause mortality, and NACE at 6-12 months were also examined.. Eleven trials that randomized a total of 15,895 elderly patients undergoing PCI to bivalirudin versus heparin were included. At 30 days, bivalirudin was associated with a reduced risk of NACE (0.86 [0.75-0.99], p = 0.04), mainly driven by reduction in major bleeding events (0.66 [0.54-0.80], p < 0.0001), as compared with heparin. On subgroup analyses based on the use of GPI in the heparin arm, benefit of major bleeding associated with bivalirudin appeared to be equally evident when GPI was used as a bailout (0.66 [0.46-0.94], p = 0.02) versus routine (0.67 [0.51-0.88], p = 0.004) adjunctive therapy with heparin. Subgroup analyses stratified by clinical presentation showed that benefit of bivalirudin in reducing NACE was even more obvious in the elderly group presenting with ST segment elevation myocardial infarction (STEMI) (0.76 [0.65-0.89], p = 0.0007), as compared with the overall (acute coronary syndrome or stable ischemic heart disease) group. No difference in MACE (0.94 [0.82-1.09], p = 0.42) was demonstrated between the two groups. Bivalirudin was associated with a similar risk of NACE (0.74 [0.39-1.42], p = 0.36) at 6 months and MACE (0.90 [0.68-1.19], p = 0.45) at 6-12 months, while a non-statistically significant trend toward lower all-cause mortality (0.70 [0.47-1.06], p = 0.09) at 1 year.. In elderly patients undergoing PCI, bivalirudin was associated with a lower risk of major bleeding events and the magnitude of benefit was not related to the use of GPI and irrespective of clinical presentation. Bivalirudin may reduce the NACE, particularly in elderly patients presenting with STEMI or in the setting of routine GPI use in the heparin arm, while no difference in MACE was demonstrated between the two groups.

Topics: Age Factors; Aged; Anticoagulants; Antithrombins; Coronary Artery Disease; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Peptide Fragments; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Factors; Time Factors; Treatment Outcome

To evaluate the efficacy of post-primary percutaneous coronary intervention (PCI) bivalirudin infusion (at full PCI dose) to prevent stent thrombosis (ST) compared with heparin monotherapy.. Early randomized controlled trials (RCTs) have shown that compared with heparin use, bivalirudin use during primary PCI is associated with an increased risk of ST. However, bivalirudin was stopped in those trials at the end of the procedure and glycoprotein IIb/IIIa inhibitors (GPIs) were routinely used with heparin. The increased risk of ST may be eliminated by continuing bivalirudin infusion post-procedure for few hours. Indeed, in most recent trials, a trend of lower ST risk has been observed with a post-procedure infusion of bivalirudin compared with heparin monotherapy (without the routine use of GPI).. Relevant RCTs were included and risk ratios (RRs) were calculated using random effect models. The primary outcome of interest was the risk of early definite ST.. Four RCTs involving 13,505 patients were included in this meta-analysis. Compared with heparin monotherapy, bivalirudin (with a post-procedure infusion) was associated with a 55% decrease in the risk of early definite ST (RR: 0.45, 95% confidence interval: 0.23-0.85; P = 0.015). There was no difference in the risk of early ST between bivalirudin (with a post-procedure infusion) and heparin with GPI.. For primary PCI, a bivalirudin-based anticoagulant strategy (with post procedure infusion) is associated with a lower risk of early definite ST compared with treatment with heparin monotherapy (without GPI).

Topics: Anticoagulants; Antithrombins; Coronary Artery Disease; Coronary Thrombosis; Drug Administration Schedule; Heparin; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Factors; Stents; Time Factors; Treatment Outcome

Patients with chronic kidney disease (CKD) have elevated bleeding and ischemic outcomes. We aim to assess the short- and long-term efficacy and safety of bivalirudin compared to heparin plus glycoprotein IIb/IIIa inhibitors (GPIs) in coronary artery disease (CAD) patients with CKD.. Randomized trials were searched in PubMed, Cochrane, and Embase databases up to January 2017. Among the trials retrieved, efficacy endpoints were defined as mortality, myocardial infarction (MI), repeat revascularization, stent thrombosis, and major adverse cardiac events (MACEs). Safety endpoints were reported as non-coronary artery bypass grafting (CABG) related major bleeding and thrombolysis in myocardial infarction (TIMI) major bleeding. Risk ratio (RR) and 95% confidence interval (CI) were calculated for each outcome using a fixed effect model.. Five studies with a total of 3796 patients were included. In short-term follow up (30 days), bivalirudin significantly reduced non-CABG related major bleeding (p=0.0004) and TIMI major bleeding (p=0.007) compared to heparin plus GPIs. No significant differences were observed in rates of mortality, MI, repeat revascularization, stent thrombosis, and MACEs between the two groups in short- and long-term follow up (6 months to 3 years). In patients with ST elevated myocardial infarction (STEMI) with concurrent CKD, the decreased non-CABG related major bleeding (p=0.04) without increasing ischemic events was also observed after short-term follow up.. (1) Bivalirudin is safer than and as effective as heparin plus GPIs in CAD patients with CKD. (2) Impaired renal function does not affect the safety benefits of bivalirudin. (3) Similar efficacy profiles were identified between the two groups after both short- and long-term follow up in the CAD patients with CKD.

Topics: Aged; Anticoagulants; Coronary Artery Disease; Female; Follow-Up Studies; Hemorrhage; Heparin; Hirudins; Humans; Kidney Function Tests; Male; Middle Aged; Myocardial Infarction; Patient Safety; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Randomized Controlled Trials as Topic; Recombinant Proteins; Renal Insufficiency, Chronic; Thrombosis; Treatment Outcome

We aimed to perform a gender-based meta-analysis of the outcome of bivalirudin versus heparin in patients undergoing percutaneous coronary interventions (PCI).. Bivalirudin has been shown to decrease major bleeding when compared to heparin ± glycoprotein IIb/IIIa inhibitors (GPI) in patients undergoing PCI. It is unclear, however, if those differences in outcomes are the same for men and women.. We included randomized controlled trials (RCTs) that compared bivalirudin to heparin with or without GPI in patients undergoing PCI and reported outcome data that were stratified by gender. Random effect model was used to pool odds ratio (OR) and 95% confidence intervals (CI).. We included 9 trials with 33,224 patients. Bivalirudin decreased major bleeding when compared to heparin plus routine GPI in both men (OR: 0.51, P < 0.001) and women (OR: 0.55, P < 0.001). However, when GPI were used selectively with heparin, the bleeding lowering effect of bivalirudin was statistically significant in men (OR: 0.69, P = 0.02) but not in women (OR: 0.71, P = 0.21). When compared to heparin ± GPI, there was a nonstatistically significant trend toward lower all-cause mortality with bivalirudin in both men (OR: 0.76, P = 0.055) and women (OR: 0.79, P = 0.21). There were no significant differences in major adverse cardiovascular events between heparin and bivalirudin in both men and women.. Bivalirudin decreases major bleeding in both men and women when compared to heparin plus routine GPI. However, when compared to heparin alone, the bleeding lowering benefit of bivalirudin is less evident in women. © 2017 Wiley Periodicals, Inc.

Topics: Aged; Anticoagulants; Antithrombins; Coronary Artery Disease; Coronary Thrombosis; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Factors; Sex Factors; Time Factors; Treatment Outcome

Bivalirudin, a direct thrombin inhibitor, is an anticoagulant commonly used in invasive cardiology procedures. It has evolved from relative obscurity, as an anticoagulation option only utilized in rare instances of allergy or resistance to heparin products, to the now preferred antithrombotic anticoagulant in the cardiac catheterization laboratory. On the way to displacing unfractionated heparin as the preferred anticoagulant for percutaneous coronary intervention, multiple studies comparing bivalirudin with heparin have consistently shown equivalent ischemic efficacy endpoints (i.e. cardiovascular death, myocardial infarction, etc.), with significant reductions in bleeding. Bleeding has been directly linked to worse hospital outcomes in cardiac patient's undergoing invasive coronary artery revascularization procedures. More recent bivalirudin studies now demonstrate reductions in mortality, which has led to a paradigm shift to bivalirudin as the anticoagulant choice both in elective and emergent coronary procedures. We present the major studies that have brought bivalirudin to the forefront of coronary artery disease, specifically coronary interventional procedures.

Topics: Antithrombins; Coronary Artery Disease; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins

Platelets play a pivotal role in the pathogenesis of coronary artery disease and myocardial infarction. Therefore, great interests have been focused in the last decades on improvement in antiplatelet therapies, that currently are regarded as main pillars in the prevention and treatment of coronary artery disease, with special attention to glycoprotein IIb-IIIa (GP IIb-IIIa) receptors, that mediates the final stage of platelet activation. GP IIb-IIIa inhibitors, especially abciximab, have been shown to improve clinical outcome in patients undergoing primary angioplasty for STEMI. Upstream administration cannot routinely recommended, but may potentially be considered among high-risk patients within the first 4 h from symptoms onset. In case of periprocedural administration of antithrombotic therapy, Bivalirudin should be considered, especially in patients at high risk for bleeding complications. Among high-risk patients with acute coronary syndromes, an early invasive strategy with selective downstream administration of GP IIb-IIIa inhibitors is the strategy of choice, whereas bivalirudin should be considered in patients at high risk for bleeding complications. Among patients with unstable angina GP IIb-IIIa inhibitors should be considered only in case of evidence of intracoronary thrombus or in case of thrombotic complications (as provisional use). Further, randomized trials are certainly needed in the era of new oral antiplatelet therapies, and with strategies to prevent bleeding complications such as larger use of radial approach, mechanical closure devices, bivalirudin, or postprocedural protamine administration to promote early sheat removal.

Topics: Acute Coronary Syndrome; Animals; Anticoagulants; Combined Modality Therapy; Coronary Artery Disease; Electrocardiography; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prognosis; Recombinant Proteins; Recurrence

Various limitations of unfractionated heparin (UFH) have triggered a search for new antithrombotic therapies for patients with coronary artery disease (CAD). Bivalirudin is a direct thrombin inhibitor with several pharmacological advantages over UFH and is currently endorsed by practice guidelines, particularly in patients with acute coronary syndromes undergoing percutaneous coronary intervention (PCI). To maximize effectiveness of an antithrombotic regimen and reduce complications, both ischemic and bleeding risks should be known when an antithrombotic strategy is chosen.. This review focuses on the safety and tolerability of bivalirudin in patients with CAD in the setting of currently approved indications. Synthesis of evidence has been made from clinical trials, systematic reviews, meta-analyses and registries (1992 - 2011). The reader is provided with an overview of pharmacological properties of bivalirudin and its efficacy, with special emphasis on its safety in patients with CAD.. Bivalirudin has an impressive safety profile in CAD patients treated with PCI. Bivalirudin is the antithrombotic of choice in suspected or verified heparin-induced thrombocytopenia. For ST elevation myocardial infarction patients undergoing primary PCI, bivalirudin should become the preferred antithrombotic agent together with early institution of antiplatelet therapy.

Topics: Angioplasty, Balloon, Coronary; Antithrombins; Coronary Artery Disease; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Practice Guidelines as Topic; Recombinant Proteins; Thrombocytopenia

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Artery Disease; Cyclic N-Oxides; Factor IXa; Fondaparinux; Heparin; Hirudins; Humans; Peptide Fragments; Polysaccharides; Pyridines; Recombinant Proteins

Abciximab is a widely studied glycoprotein IIb/IIIa inhibitor, specifically in the setting of patients undergoing percutaneous coronary intervention (PCI). The populations studied have included patients with non-ST-segment acute coronary syndromes, ST-segment elevation myocardial infarction, and elective PCI. This large amount of information provides a clear efficacy and safety profile of the drug, although a few questions on the use of abciximab still exist, particularly on its use and preference in the setting of newer antiplatelet and antithrombotic medications. In this article we review the most relevant data from randomized clinical trials with abciximab in patients undergoing PCI and discuss the recent guideline recommendation on use during PCI.

Topics: Abciximab; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Clopidogrel; Coronary Artery Disease; Electrocardiography; Hirudins; Humans; Immunoglobulin Fab Fragments; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Randomized Controlled Trials as Topic; Recombinant Proteins; Ticlopidine

Chronic kidney disease is associated with an increased risk of ischemic and bleeding events after percutaneous coronary intervention (PCI). The direct thrombin inhibitor bivalirudin reduces these combined events. We sought to assess whether this benefit was influenced by renal function. A meta-analysis of 3 randomized trials (n = 5,035) comparing bivalirudin with heparin during PCI, stratified by estimated creatinine clearance using the Cockcroft-Gault equation (>90 [n = 1,578], 90 to 60 [n = 2,163], 59 to 30 [n = 1,255], and <30 ml/min [n = 39]), was conducted. The composite end points of death, myocardial infarction or revascularization, hemorrhage, and combined ischemic or bleeding events were assessed. A common odds ratio for each creatinine clearance strata was estimated with a random-effects model. The interaction between renal impairment and benefit from bivalirudin was assessed. Adverse ischemic and bleeding events increased with decreasing renal function. The relative benefit of bivalirudin with respect to ischemic and bleeding events was maintained within each stratum. The absolute benefit in terms of ischemic and bleeding complications increased with decreasing creatinine clearance (normal 2.2%, mild 5.8%, moderate 7.7%, severe 14.4%; p trend <0.001, interaction p = 0.044). Renal dysfunction remains a prevalent risk factor for ischemic and bleeding events in patients who undergo PCI. Bivalirudin provides greater absolute benefit in patients with impaired renal function.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Coronary Artery Disease; Creatinine; Female; Fibrinolytic Agents; Hirudins; Humans; Hypertension; Ischemia; Kidney Failure, Chronic; Male; Middle Aged; Peptide Fragments; Postoperative Hemorrhage; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Factors; Sex Factors

Topics: Angioplasty, Balloon, Coronary; Combined Modality Therapy; Coronary Artery Disease; Dose-Response Relationship, Drug; Fibrinolytic Agents; Heparin; Hirudin Therapy; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Risk Factors; Smoking; Treatment Outcome; United States

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

Despite dual antiplatelet therapy patients undergoing percutaneous coronary intervention (PCI) continue to experience periprocedural ischemic events. In addition, all currently used antithrombotic drugs increase the bleeding risk. Thus, there is an unmet clinical need for antithrombotic strategies with improved efficacy and no increase in bleeding. Revacept is a novel, lesion-directed antithrombotic drug that does not interfere with the function of circulating platelets. This dimeric fusion protein of the extracellular domain of glycoprotein VI (the major platelet collagen receptor) and the human Fc-fragment inhibits collagen-mediated platelet adhesion and subsequent aggregation at the site of vascular injury. The randomized, double-blinded, phase II ISAR-PLASTER trial is based on extensive preclinical evaluation of Revacept and a favorable first-in-man trial. A total of 332 patients with stable coronary artery disease undergoing elective PCI will be randomized to either Revacept 160 mg, Revacept 80 mg, or placebo administered as single intravenous infusion directly before the intervention, on top of standard dual antiplatelet therapy and either heparin or bivalirudin, based on local practice and current guidelines. The primary endpoint is the composite of death or myocardial injury (defined as increase in high sensitivity troponin T ≥ 5 times the upper limit of normal) at 48 hours. The safety endpoint is bleeding of class 2 or higher according to the Bleeding Academic Research Consortium at 30 days. This phase II randomized, double blind trial will assess for the first time the efficacy and safety of Revacept-a lesion-directed inhibitor of platelet adhesion-in patients undergoing elective PCI.

Topics: Adult; Aged; Aged, 80 and over; Blood Platelets; Coronary Artery Disease; Double-Blind Method; Dual Anti-Platelet Therapy; Elective Surgical Procedures; Female; Fibrinolytic Agents; Germany; Glycoproteins; Hemorrhage; Heparin; Hirudins; Humans; Immunoglobulin Fc Fragments; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Placebos; Platelet Aggregation; Recombinant Proteins; Survival Analysis; Young Adult

To compare bleeding and clinical events of patients with stable angina or silent ischemia undergoing percutaneous coronary intervention (PCI) treated with unfractionated heparin (UFH) or bivalirudin.. Few direct comparisons between UFH monotherapy versus bivalirudin exist for patients with stable ischemic heart disease undergoing PCI.. A prospective, investigator-initiated, single-center, single-blinded, randomized trial of UFH versus bivalirudin was conducted. The primary endpoint was all bleeding (major and minor) from index-hospitalization to 30 days post discharge. Secondary endpoints included major adverse cerebral and cardiovascular events (MACCE) and net adverse clinical events (NACE).. Two-hundred-sixty patients were randomized for treatment with either UFH (n = 123) (47%) or bivalirudin (n = 137) (53%) There were no significant differences in baseline clinical and angiographic characteristics between the two groups. Primary endpoint was similar in both groups (10.9% with bivalirudin vs 7.3% with UFH [P = 0.31]). Major bleeding rates were 5.8% and 2.4%, respectively (P = 0.17). There was a higher MACCE (3.5% vs 0%, P = 0.03) and NACE (8.8% vs 2.4%, P = 0.03) rate with bivalirudin compared to UFH, respectively. Bivalirudin had increased odds of NACE (OR = 3.65, 95% CI: 1.00-13.3.6). Death and stent thrombosis rates were low and similar in both groups. Radial access was associated with fewer bleeding events compared to femoral access but not statistically significant (P = 0.29).. Among patients with stable angina or silent ischemia, there was no difference between UFH and bivalirudin in bleeding rates up to 30-days post-PCI. MACCE and NACE were higher among the bivalirudin group. Radial access was associated with a numerically lower rate of bleeding compared with femoral access.

Topics: Aged; Anticoagulants; Coronary Artery Disease; Drug Monitoring; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Ischemia; Peptide Fragments; Percutaneous Coronary Intervention; Prospective Studies; Recombinant Proteins; Thrombosis; Treatment Outcome

This study sought to assess the safety and the efficacy of bivalirudin compared with unfractionated heparin (UFH) alone in the subset of patients at increased risk of bleeding undergoing transfemoral elective percutaneous coronary intervention (PCI).. Bivalirudin, a synthetic direct thrombin inhibitor, determines a significant decrease of in-hospital bleeding following PCI.. This is a single-center, investigator-initiated, randomized, double-blind, controlled trial. Consecutive biomarker-negative patients at increased bleeding risk undergoing PCI through the femoral approach were randomized to UFH (UFH group; n = 419) or bivalirudin (bivalirudin group; n = 418). The primary endpoint was the rate of in-hospital major bleeding.. The primary endpoint occurred in 11 patients (2.6%) in the UFH group versus 14 patients (3.3%) in the bivalirudin group (odds ratio: 0.78; 95% confidence interval: 0.35 to 1.72; p = 0.54). Distribution of access-site and non-access-site bleeding was 18% and 82% in the UFH group versus 50% and 50% in the bivalirudin group (p = 0.10).. The results of this randomized study, carried out at a single institution, suggest that there is no difference in major bleeding rate between bivalirudin and UFH in increased-risk patients undergoing transfemoral PCI. (Novel Approaches in Preventing and Limiting Events III Trial: Bivalirudin in High-Risk Bleeding Patients [NAPLES III]; NCT01465503).

Topics: Aged; Aged, 80 and over; Coronary Artery Disease; Double-Blind Method; Female; Femoral Artery; Hemorrhage; Heparin; Hirudins; Humans; Italy; Male; Peptide Fragments; Percutaneous Coronary Intervention; Prospective Studies; Punctures; Recombinant Proteins; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

The aim of this study was to examine the efficacy and bleeding outcomes of cangrelor in patients in the CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI]) who underwent percutaneous coronary intervention with bivalirudin.. Cangrelor is a potent intravenous P2Y12 inhibitor with rapid onset and offset. In the CHAMPION PHOENIX, cangrelor compared with clopidogrel significantly reduced 48-h ischemic events including stent thrombosis, without increasing major bleeding. Bivalirudin has demonstrated ischemic outcomes similar to those with heparin plus glycoprotein IIb/IIIa inhibition, with reduced bleeding but increased early stent thrombosis.. In the modified intent-to-treat population, 2,059 patients (18.8%) received bivalirudin, with 1,014 patients in the cangrelor treatment arm and 1,045 in the clopidogrel treatment arm.. At 48 h, the primary endpoint of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis was lower with cangrelor versus clopidogrel (48 [4.7%] vs. 70 [6.7%]; odds ratio [OR]: 0.68, p = 0.047). Death was similar in both arms (2 [0.2%] vs. 2 [0.2%]). Myocardial infarction was reduced by cangrelor (37 [3.6%] vs. 59 [5.6%]; OR: 0.63, p = 0.03), as was death/myocardial infarction (39 [3.8%] vs. 61 [5.8%]; OR: 0.65, p = 0.04). Cangrelor was associated with a nonsignificant trend toward less stent thrombosis (7 [0.7%] vs. 15 [1.4%]; OR: 0.48, p = 0.10), which was evident within 2 h after percutaneous coronary intervention (p = 0.057). GUSTO (Global Use of Strategies to Open Occluded Arteries) severe bleeding was similar in both arms (2 of 1,021 [0.2%] vs. 2 of 1,055 [0.2%]) as were other bleeding definitions and transfusions. Efficacy and safety results were consistent in patients with stable angina, non-ST-segment elevation acute coronary syndrome, and ST-segment elevation myocardial infarction (p for interaction: 0.62 and 0.29).. Cangrelor may offer an attractive benefit risk profile when used in combination with bivalirudin.

Topics: Adenosine Monophosphate; Aged; Anticoagulants; Chi-Square Distribution; Clopidogrel; Coronary Artery Disease; Coronary Thrombosis; Double-Blind Method; Female; Hemorrhage; Hirudins; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Recombinant Proteins; Risk Factors; Stents; Ticlopidine; Time Factors; Treatment Outcome

Bivalirudin has emerged as a meaningful alternative to heparin in patients undergoing percutaneous coronary intervention (PCI). To date, it is unclear whether bivalirudin has advantages in patients undergoing rotational atherectomy (RA).. The current subgroup analysis of the ROTAXUS trial compared patients receiving bivalirudin (n=129) to those receiving unfractionated heparin (UFH) (n=111). Efficacy was assessed by the frequency of periprocedural myocardial infarction (MI) and safety by the frequency of major access-site bleeding (ASB). Baseline characteristics were similar. Periprocedural MI occurred less frequently in the bivalirudin group (22% vs. 37.5%, p=0.02), while ASB did not differ significantly (2.3% vs. 5.5%, p=0.20). This effect was larger in the RA group, where bivalirudin significantly reduced periprocedural MI (15.7% vs. 38.7%, p=0.01) with a trend towards reduced major ASB (2.9% vs. 10.2%, p=0.09). In the control group without RA, bivalirudin was not superior to UFH regarding periprocedural MI (28.6% vs. 36.6%, p=0.42) and major ASB (1.7% vs. 1.7%, p=0.99).. This analysis suggests a differential benefit of bivalirudin in patients treated with RA. Patients receiving bivalirudin during RA showed significantly less periprocedural MI and fewer ASB compared to patients treated with UFH.

Topics: Aged; Anticoagulants; Antithrombins; Atherectomy, Coronary; Coronary Artery Disease; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Treatment Outcome

Although lesion complexity is predictive of outcomes after balloon angioplasty, it is unclear whether complex lesions continue to portend a worse prognosis in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) with contemporary interventional therapies. We sought to assess the impact of angiographic lesion complexity, defined by the modified American College of Cardiology/American Heart Association classification, on clinical outcomes after PCI in patients with ACS and to determine whether an interaction exists between lesion complexity and antithrombin regimen outcomes after PCI. Among the 3,661 patients who underwent PCI in the Acute Catheterization and Urgent Intervention Triage strategy study, patients with type C lesions (n = 1,654 [45%]) had higher 30-day rates of mortality (1.2% vs 0.6%, p = 0.049), myocardial infarction (9.2% vs 6.3%, p = 0.0006), and unplanned revascularization (4.3% vs 3.1%, p = 0.04) compared with those without type C lesions. In multivariate analysis, type C lesions were independently associated with myocardial infarction (odds ratio [95% confidence interval] = 1.37 [1.04 to 1.80], p = 0.02) and composite ischemia (odds ratio [95% confidence interval] = 1.49 [1.17 to 1.88], p = 0.001) at 30 days. Bivalirudin monotherapy compared with heparin plus a glycoprotein IIb/IIIa inhibitor reduced major bleeding complications with similar rates of composite ischemic events, regardless of the presence of type C lesions. There were no interactions between antithrombotic regimens and lesion complexity in terms of composite ischemia and major bleeding (p [interaction] = 0.91 and 0.80, respectively). In conclusion, patients with ACS with type C lesion characteristics undergoing PCI have an adverse short-term prognosis. Treatment with bivalirudin monotherapy reduces major hemorrhagic complications irrespective of lesion complexity with comparable suppression of adverse ischemic events as heparin plus glycoprotein IIb/IIIa inhibitor.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Coronary Angiography; Coronary Artery Disease; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Myocardial Revascularization; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prognosis; Recombinant Proteins; Severity of Illness Index; Treatment Outcome

A major concern of stent implantation after percutaneous coronary intervention (PCI) is acute stent thrombosis. Effective inhibition of periprocedural platelet function in patients with coronary artery disease (CAD) leads to an improved outcome. In this study, we examined the periprocedural platelet reactivity after administrating bivalirudin during PCI compared to unfractionated heparin (UFH) administration. Further, the effect of bivalirudin on induced tissue factor (TF) expression in smooth muscle cells (SMC) was determined.. Patients with CAD (n = 58) and double antithrombotic medication were treated intraprocedural with UFH (n = 30) or bivalirudin (n = 28). Platelet activation markers were flow cytometrically measured before and after stenting. The expression of TF in SMC was determined by real-time PCR and Western blotting. The thrombogenicity of platelet-derived microparticles and SMC was assessed via a TF activity assay.. Bivalirudin significantly diminished the agonist-induced platelet reactivity post-PCI. Compared to UFH treatment, the adenosine diphosphate (ADP) and thrombin receptor-activating peptide (TRAP)-induced thrombospondin expression post-PCI was reduced when bivalirudin was administrated during intervention. In contrast to UFH, bivalirudin reduced the P-selectin expression of unstimulated and ADP-induced platelets post-PCI. Moreover, bivalirudin inhibited the thrombin-, but not FVIIa- or FVIIa/FX-induced TF expression and pro-coagulant TF activity of SMC. Moreover, bivalirudin reduced the TF activity of platelet-derived microparticles postinduction with TRAP or ADP.. Bivalirudin is better than UFH in reducing periprocedural platelet activation. Moreover, thrombin-induced TF expression is inhibited by bivalirudin. Thus, bivalirudin seems to be a better anticoagulant during PCI than UFH.

Topics: Aged; Anticoagulants; Antithrombins; Biomarkers; Blood Platelets; Blotting, Western; Cells, Cultured; Coronary Artery Disease; Factor VIIa; Factor X; Female; Flow Cytometry; Germany; Heparin; Hirudins; Humans; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; P-Selectin; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Activation; Platelet Function Tests; Real-Time Polymerase Chain Reaction; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stents; Tetraspanin 30; Thromboplastin; Thrombospondins; Treatment Outcome

Bivalirudin, a direct thrombin inhibitor, is as effective as unfractionated heparin (UFH), with decreased bleeding in patients with acute coronary syndromes who undergo percutaneous coronary intervention (PCI). The aim of this study was to evaluate the effectiveness of bivalirudin versus UFH in selected PCI patients at high bleeding risk. Four hundred one consecutive patients who underwent PCI fulfilling ≥ 1 enrollment criterion (age >75 years, chronic renal failure, and diabetes mellitus) were randomized to bivalirudin (bolus 0.75 mg/kg followed by infusion during the procedure; n = 198) or UFH (75 IU/kg; n = 203). In the overall population, 39% were aged >75 years, 22% had renal failure, 63% had diabetes, and 29% had acute coronary syndromes. The primary efficacy end point was the 30-day incidence of major adverse cardiac events (cardiac death, myocardial infarction, stent thrombosis, or target vessel revascularization). The primary safety end point was the occurrence of any bleeding or entry-site complications after PCI. All patients were preloaded with clopidogrel 600 mg. Glycoprotein IIb/IIIa inhibitors were used at the operators' discretion. Thirty-day major adverse cardiac event rates were 11.1% in the bivalirudin group and 8.9% in the UFH group (p = 0.56); the primary efficacy end point was reached mainly because of periprocedural myocardial infarction; 1 patient in the bivalirudin group had stent thrombosis. Occurrence of the primary safety end point was 1.5% in the bivalirudin group and 9.9% in the UFH group (p = 0.0001); this benefit was essentially driven by the prevention of entry-site hematomas >10 cm (0.5% vs 6.9%, p = 0.002). In conclusion, Anti-Thrombotic Strategy for Reduction of Myocardial Damage During Angioplasty-Bivalirudin vs Heparin (ARMYDA-7 BIVALVE) indicates that bivalirudin, compared with UFH, causes significantly lower bleeding and has a similar incidence of major adverse cardiac events in patients with older age, diabetes mellitus, or chronic renal failure who undergo PCI.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Antithrombins; Coronary Artery Disease; Diabetes Complications; Drug Therapy, Combination; Female; Heart Diseases; Heparin; Hirudins; Humans; Incidence; Male; Myocardial Infarction; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Postoperative Hemorrhage; Recombinant Proteins; Renal Insufficiency; Treatment Outcome

To determine whether statin therapy influences the efficacy of thrombin inhibitor bivalirudin or unfractionated heparin (UFH) during PCI.. The post-hoc analysis of the ISAR-REACT 3 Trial included 4,570 patients: 3,106 patients were on statin therapy and 1,464 patients were not on statin therapy at the time of PCI procedure.. The primary outcome of this analysis was the 30-day composite of death, myocardial infarction, target vessel revascularization (TVR) or major bleeding.. The primary outcome occurred in 7.9% patients (n = 246) in the statin group versus 9.8% (n = 143) in the non-statin group (P = 0.036). There was an interaction in univariate (P = 0.028) and multivariable (P = 0.026) analysis between pre-PCI statin therapy and the type of antithrombotic therapy regarding myocardial infarction. In the statin group, bivalirudin significantly reduced the incidence of major bleeding (2.6 vs. 4.3%, P = 0.013) with no significant difference in the incidence of myocardial infarction (4.9 vs. 5.2%; P = 0.73) compared with UFH. In the non-statin group, bivalirudin was inferior to UFH regarding the incidence of myocardial infarction (7.1 vs. 4.1%, P = 0.013), yet major bleeding remained lower among bivalirudin-treated patients (4.0 vs. 5.2%, P = 0.25).. This post-hoc analysis suggests the existence of an interaction between statin therapy before PCI and antithrombotic therapy during PCI. Patients receiving bivalirudin therapy at the time of PCI showed less periprocedural myocardial infarction when on pre-PCI statin therapy which has to be investigated in further studies.

Topics: Aged; Angioplasty, Balloon, Coronary; Antithrombins; Coronary Artery Disease; Drug Interactions; Female; Heparin; Hirudins; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Peptide Fragments; Recombinant Proteins; Treatment Outcome

Compared to unfractionated heparin (UFH), bivalirudin decreases bleeding during percutaneous coronary interventions (PCIs). We sought to investigate the association between periprocedural bleeding and 1-year mortality as a function of antithrombotic therapy with bivalirudin or UFH. This analysis of the association between bleeding with bivalirudin or UFH and 1-year mortality included the 4,570 patients with negative biomarkers enrolled in the Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT 3) trial. Major or minor bleeding occurred in 555 patients (12.1%): 225 patients treated with bivalirudin (9.8%) and 330 patients treated with UFH (14.5%, p <0.001). There were 82 deaths (1.8%) within the first year after PCI: 29 deaths occurred in patients who had bled, and 53 deaths occurred in patients who had not bled (Kaplan-Meier estimates of 1-year mortality 5.2% and 1.3%, odds ratio 4.12, 95% confidence interval 2.59 to 6.54, p <0.001). One year after PCI, there were 15 deaths in patients who bled with bivalirudin versus 14 deaths in patients who bled with UFH (Kaplan-Meier estimates of 1-year mortality 6.7% vs 4.2%, odds ratio 1.61, 95% confidence interval 0.76 to 3.40, p = 0.20). Major bleeding occurred in 70 patients (3.0%) treated with bivalirudin and 104 patients treated with UFH (4.5%, p = 0.008). One-year mortality was 11.4% (n = 8) in patients with major bleeding with bivalirudin versus 4.8% (n = 5) in patients with major bleeding with UFH (p = 0.10). In conclusion, these data suggest that in patients with negative biomarkers undergoing PCI, bivalirudin decreases bleeding after PCI compared to UFH, without affecting 1-year mortality in those who had bled.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Cohort Studies; Coronary Artery Disease; Female; Heparin; Hirudins; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Peptide Fragments; Postoperative Hemorrhage; Recombinant Proteins; Risk Factors; Stents; Treatment Outcome

Bivalirudin demonstrated similar efficacy but resulted in a lower rate of bleeding compared to unfractionated heparin (UFH) plus platelet glycoprotein IIb/IIIa inhibitors in patients undergoing percutaneous coronary intervention. It has not been clearly evaluated whether this can also be applied to patients with diabetes mellitus. A total of 335 consecutive patients with diabetes mellitus referred for elective percutaneous coronary intervention were randomized in the Novel Approaches for Preventing or Limiting EventS (NAPLES) trial to receive bivalirudin monotherapy or UFH plus routine tirofiban. The primary composite end point (30-day composite incidence of death, urgent repeat revascularization, myocardial infarction, and all bleeding) was lower in the bivalirudin group than in the UFH plus tirofiban group (18.0% vs 31.5%, odds ratio 0.47, 95% confidence interval 0.28 to 0.79, p = 0.004). No death, urgent revascularization, or Q-wave myocardial infarction occurred. The rate of non-Q-wave myocardial infarction was similar in the 2 groups (10.2% in the bivalirudin group vs 12.5% in the UFH plus tirofiban group, p = 0.606). In contrast, fewer patients in the bivalirudin group experienced bleeding (8.4% vs 20.8%, odds ratio 0.34, 95% confidence interval 0.18 to 0.67, p = 0.002). This difference was mainly ascribed to the lower rate of minor bleeding (7.8% in the bivalirudin group vs 18.5% in the UFH plus tirofiban group, odds ratio 0.37, 95% confidence interval 0.19 to 0.74, p = 0.005), although the rate of major bleeding in the 2 groups was comparable (0.6% vs 2.4%, respectively; p = 0.371). In conclusion, in patients with diabetes mellitus undergoing elective percutaneous coronary intervention, the strategy of bivalirudin monotherapy compared to UFH plus routine tirofiban is safe and feasible and associated with a significant reduction of in-hospital bleeding.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Artery Disease; Diabetes Mellitus; Drug Therapy, Combination; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Prospective Studies; Recombinant Proteins; Retreatment; Thrombocytopenia; Tirofiban; Tyrosine

To evaluate the safety and efficacy of bivalirudin based therapy among patients undergoing percutaneous coronary intervention (PCI) for stable coronary artery disease in a large multicenter registry.. The REPLACE I trial demonstrated the non-inferiority of a strategy of bivalirudin compared with heparin and glycoprotein (GP) IIbIIIa inhibition in patients undergoing PCI. There is a paucity of outcome data with bivalirudin use in the setting of real-world PCI practice.. We evaluated the outcome of 11,719 patients who underwent elective PCI for stable coronary artery disease (CAD) from 2002 to 2004 in a large regional consortium, and who were treated with bivalirudin (n = 2051) or with heparin and GP IIbIIIa inhibitors (n = 9,668). The primary endpoints were transfusion and in-hospital major adverse cardiovascular events (MACE) defined as the composite of death, MI, stroke, and any coronary artery bypass grafting (CABG) or target lesion revascularization.. Compared with patients who received heparin plus GP IIbIIIa inhibitors, patients who received bivalirudin had a similar incidence of post-procedural MI, stroke, in-hospital death, MACE (2.88 vs. 2.48, P = 0.30), or transfusion (2.83% vs. 2.41%, P = 0.27). Patients at greater risk of bleeding were more likely to be treated with bivalirudin. After adjusting for the propensity to receive bivalirudin and for baseline co-morbidities, there was no difference in the odds of MACE or the need for transfusion between the two groups.. Compared with heparin plus GP IIbIIIa inhibition, use of bivalirudin in patients undergoing PCI for stable CAD is associated with similar ischemic and bleeding complications. Given the ease of administration and lower cost, bivalirudin provides an attractive treatment option in this patient population.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Artery Disease; Elective Surgical Procedures; Female; Heparin; Hirudins; Humans; Male; Michigan; Middle Aged; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Registries; Risk Factors; Time Factors; Treatment Outcome

The objective of this study was to confirm that the efficacy and safety of percutaneous coronary intervention (PCI) in diabetic patients are not compromised by a bivalirudin-based antithrombotic strategy.. Previous studies have shown a survival benefit with use of platelet glycoprotein (GP) IIb/IIIa inhibitors in diabetic patients undergoing PCI. The Randomized Evaluation in Percutaneous Coronary Intervention Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial showed the non-inferiority of a strategy of bivalirudin with provisional GP IIb/IIIa inhibition compared with routine GP IIb/IIIa inhibition. The relative efficacy of these two strategies in diabetic patients has not been studied.. We evaluated the diabetic patients enrolled in the REPLACE-2 trial to assess the impact of these antithrombotic strategies on the short- and long-term outcome after PCI.. The REPLACE-2 trial enrolled 1,624 diabetic patients and 4,368 non-diabetic patients. Compared with non-diabetic patients, diabetic patients had similar short-term outcome but higher mortality at 1 year (3.06% vs. 1.85%, p = 0.004). There was no difference in short-term or long-term ischemic events among the diabetic patients randomized to the two arms. Specifically, the 1-year mortality rate was non-significantly lower in the bivalirudin arm, suggesting no differential survival impact of the two strategies (2.3% vs. 3.9%). There was less minor bleeding in the bivalirudin arm in diabetic patients (12.6% vs. 24.4%, p < 0.001), whereas no difference was seen in the incidence of major bleeding (3.0% vs. 3.3%, p = 0.69).. Compared with routine GP IIb/IIIa inhibition, the use of bivalirudin with provisional GP IIb/IIIa inhibitors in diabetic patients is associated with no differences in clinical outcomes at 30 days, a trend toward lesser mortality at 1 year, and a reduction in minor bleeding.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Artery Disease; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Treatment Outcome

Bivalirudin (Angiomax) is increasingly used as a substitute for heparin in a variety of percutaneous coronary interventions, and data on its usage in saphenous vein graft interventions are limited. This retrospective, observational study evaluated the efficacy and safety of bivalirudin compared with heparin as an antithrombotic regimen in patients who underwent saphenous vein graft intervention with distal protection devices. We found that bivalirudin use is clinically safe and feasible, with fewer vascular and ischemic complications compared with heparin.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Coronary Artery Disease; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Postoperative Complications; Recombinant Proteins; Retrospective Studies; Saphenous Vein; Stents; Thrombosis; Treatment Outcome

To characterize effects of bivalirudin compared with unfractionated heparin plus eptifibatide on inflammation, and thrombin generation and activity after percutaneous coronary intervention.. We measured the concentration in blood of fibrinopeptide A, prothrombin fragment 1+2, soluble CD40 ligand, interleukin 1 receptor antagonist, interleukin 6, and high sensitivity C-reactive protein in 63 patients treated with aspirin and clopidogrel and undergoing elective percutaneous coronary intervention, who were randomized to treatment with either bivalirudin (n=34) or unfractionated heparin plus eptifibatide (n=29).. Neither generation nor activity of thrombin increased 10 min after percutaneous coronary intervention in patients randomized to bivalirudin or unfractionated heparin plus eptifibatide. However, prothrombin fragment 1+2 increased modestly and comparably in both groups after 1 day. Inflammation, reflected by concentrations of interleukin 6 and high sensitivity C-reactive protein in blood, increased similarly 1 day after percutaneous coronary intervention in patients treated with either regimen. In a subset of patients (n=12 in each group) from whom blood was obtained 30 days after percutaneous coronary intervention, the concentration of high sensitivity C-reactive protein was lower in those who had been treated with bivalirudin (by 3.5 mg/l, P=0.002).. The early effects on inflammation and thrombin generation and activity are similar after treatment with bivalirudin alone compared with unfractionated heparin plus eptifibatide in patients treated with aspirin and clopidogrel who are undergoing percutaneous coronary intervention for symptoms of stable angina. The decreased concentration of high sensitivity C-reactive protein seen 30 days after percutaneous coronary intervention in those treated with bivalirudin is consistent with greater attenuation of inflammation that may have contributed to the trend toward reduced mortality 1 year later in those treated with bivalirudin in REPLACE-2.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; C-Reactive Protein; CD40 Ligand; Combined Modality Therapy; Coronary Artery Disease; Eptifibatide; Female; Fibrinopeptide A; Heparin; Hirudins; Humans; Interleukin-6; Male; Middle Aged; Peptide Fragments; Peptides; Platelet Aggregation Inhibitors; Protein Precursors; Prothrombin; Receptors, Interleukin-1; Recombinant Proteins; Thrombin; Treatment Outcome

Three hundred nine patients were followed during their recovery area stay after percutaneous coronary intervention. Recovery area times for patients who received bivalirudin during percutaneous coronary intervention showed an average reduction in total recovery area length of stay of 36 minutes (p <0.0001) compared with patients who received heparin alone. This reduction was also seen when compared with the heparin + abciximab group (46-minute reduction, p = 0.0007), and the heparin + eptifibatide group (35-minute reduction, p = 0.0005). Patients who received bivalirudin took significantly less time for the activated clotting time (ACT) to normalize despite significantly higher average ACTs and significantly fewer subtherapeutic ACTs.

Topics: Abciximab; Aged; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Anticoagulants; Antithrombins; Coronary Artery Disease; Drug Therapy, Combination; Eptifibatide; Female; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Length of Stay; Male; Middle Aged; Peptide Fragments; Peptides; Recombinant Proteins; Treatment Outcome

To assess the effectiveness and safety of bivalirudin compared with heparin monotherapy in elderly patients undergoing percutaneous coronary intervention (PCI).. Bivalirudin is recommended for periprocedural use in patients undergoing PCI who are of high bleeding risk. However, its safe and efficacious use in elderly patients, a typical high bleeding risk cohort, in real world practice is yet to be reported.. In this single center, real-world observational study, 4736 consecutive elderly patients who underwent PCI were enrolled. Of these, 1240 were treated with bivalirudin and 3496 with heparin according to the periprocedural anticoagulation strategies of PCI. The primary outcome was 12-month net adverse clinical events (NACE) defined as a composite of cardiac death, myocardial infarction, stroke, revascularization, or any bleeding. Propensity score matching (PSM) was used to balance baseline characteristics between groups.. After PSM, bivalirudin was found to be associated with lower rates of NACE (19.1% vs. 24.7%, p = 0.002), cardiac death (2.7% vs. 4.3%, p = 0.038), and any bleeding (10.0% vs. 12.9%, p = 0.023) compared to heparin monotherapy. No differences were found in the incidences of myocardial infarction, stroke, revascularization, stent thrombosis (0.1% vs. 0.1%, p = 1.000), and major bleedings (0.5% vs. 0.5%, p = 1.000) between the two patient groups.. In this real-world observational study, periprocedural use of bivalirudin in elderly patients who underwent PCI was associated with less cardiac death and any bleeding compared to heparin monotherapy, without increased risk of stent thrombosis.

Topics: Aged; Anticoagulants; Coronary Artery Disease; Death; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Stroke; Thrombosis; Treatment Outcome

The present study aimed to comprehensively investigate the occurrence and risk factors of adverse events (AEs) or adverse drug reactions (ADRs) (especially for thrombocytopenia and bleeding) in Chinese female patients receiving bivalirudin during percutaneous coronary intervention (PCI).. A total of 918 female patients from 27 Chinese medical centers took bivalirudin as anticoagulant for PCI were enrolled in this prospective, multi-center, intensive monitoring study. Safety data (AEs, ADRs, thrombocytopenia and bleeding) were collected from admission to 72 h post bivalirudin administration; then, patients were followed up at the 30. One hundred and twenty (13.1%) patients occurred AEs, among which 7 (0.8%) cases experienced severe AEs, and 2 (0.2%) cases died. Besides, 40 (4.4%) patients occurred bivalirudin-related ADRs, in which 3 (0.3%) cases experienced severe ADRs, but 0 (0.0%) cases died. It was of note that 27 (2.9%) and 13 (1.4%) patients experienced thrombocytopenia and bleeding, respectively. Subsequent multivariate analyses observed that: clinical presentation of spontaneous coronary artery dissection (SCAD) (odds ratio (OR) = 3.191, P = 0.004), CRUSADE high risk (OR = 2.075, P = 0.031), multiple culprit vessel (OR = 2.328, P = 0.019) independently correlated with higher risk of bivalirudin-related ADRs; clinical presentation of SCAD (OR = 4.388, P = 0.002) and multiple culprit vessel (OR = 2.974, P = 0.010) independently linked with raised thrombocytopenia risk; history of diabetes mellitus (OR = 5.227, P = 0.007) and CRUSADE high risk (OR = 4.475, P = 0.016) were independent factor related to elevated bleeding risk.. Bivalirudin is well tolerated with low ADRs, thrombocytopenia and bleeding incidences in Chinese female patients undergoing PCI.

Topics: Aged; Antithrombins; China; Coronary Artery Disease; Female; Hemorrhage; Hirudins; Humans; Incidence; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Prospective Studies; Recombinant Proteins; Risk Assessment; Risk Factors; Sex Factors; Thrombocytopenia; Time Factors; Treatment Outcome

The efficacy and safety of continued bivalirudin infusion after percutaneous coronary intervention (PCI) remains uncertain. We sought to investigate the association between post-PCI bivalirudin infusion and the risk of net adverse clinical events (NACE) at 30 days.. In the GLOBAL LEADERS study, all patients who received bivalirudin during PCI were categorized according to the use of bivalirudin infusion after the procedure. The primary endpoint of the present analysis was NACE [a composite of all-cause death, any stroke, any myocardial infarction, all revascularization, and bleeding assessed according to the Bleeding Academic Research Consortium (BARC) criteria Type 3 or 5] at 30 days. The key safety endpoint was BARC Type 3 or 5 bleeding and definite stent thrombosis. Of 15 968 patients, 13 870 underwent PCI with the use of bivalirudin. In total, 7148 patients received continued bivalirudin infusion after procedure, while 6722 patients received standard care. After propensity score covariate adjustment, the risk of NACE did not significantly differ between two treatments after PCI [continued bivalirudin infusion vs. no bivalirudin infusion: 3.2% vs. 3.1%, adjusted hazard ratio (aHR) 1.35, 95% confidence interval (CI) 0.99-1.84, P = 0.06] nor the BARC Type 3 or 5 bleeding (0.7% vs. 0.7%, aHR 0.89, 95% CI 0.44-1.79; P = 0.743) and definite stent thrombosis (0.5% vs. 0.3%, aHR 1.71, 95% CI 0.77-3.81, P = 0.189). However, continued bivalirudin infusion was associated with an increased risk of NACE and definite stent thrombosis in ST-elevation myocardial infarction (STEMI) patients.. In an all-comers population undergoing PCI, there was no significant difference in the risk of NACE at 30 days between continued bivalirudin infusion vs. no bivalirudin infusion after procedure but continued bivalirudin infusion was associated with a higher risk of NACE in STEMI patients when compared with no infusion.

Topics: Aged; Antithrombins; Coronary Artery Disease; Coronary Thrombosis; Female; Hemorrhage; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Stents; Time Factors; Treatment Outcome

Bleeding risk stratification is an unresolved issue in older adults. Anemia may reflect subclinical blood losses that can be exacerbated after percutaneous coronary intervention . We sought to prospectively determine the contribution of anemia to the risk of bleeding in 448 consecutive patients aged 75 or more years, treated by percutaneous coronary interventions without concomitant indication for oral anticoagulation. We evaluated the effect of WHO-defined anemia on the incidence of 1-year nonaccess site-related major bleeding. The prevalence of anemia was 39%, and 13.1% of anemic and 5.2% of nonanemic patients suffered a bleeding event (hazard ratio 2.75, 95% confidence interval 1.37 to 5.54, p = 0.004). Neither PRECISE-DAPT nor CRUSADE scores were superior to hemoglobin for the prediction of bleeding. In conclusion, anemia is a powerful predictor of bleeding with potential utility for simplifying tailoring therapies.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Anemia; Angina, Unstable; Anticoagulants; Antithrombins; Aspirin; Cause of Death; Clopidogrel; Comorbidity; Coronary Artery Disease; Drug-Eluting Stents; Female; Gastrointestinal Hemorrhage; Hemorrhage; Heparin; Hirudins; Humans; Intracranial Hemorrhages; Kaplan-Meier Estimate; Male; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Care; Postoperative Hemorrhage; Prasugrel Hydrochloride; Proportional Hazards Models; Prospective Studies; Recombinant Proteins; Risk Assessment; Stents; Ticagrelor; Urologic Diseases

We attempted to test the feasibility of application of the MADS classification system in the largest stent trial to date and evaluate the preliminary clinical implications of this approach.. In the randomized GLOBAL LEADERS trial, testing two different antiplatelet strategies in patients undergoing PCI with bivalirudin and biolimus-eluting stents, the e-CRF was dedicated to bifurcation treatment according to the MADS classification. Based on this e-CRF, the techniques used for bifurcations treatment in GLOBAL LEADERS were described and compared with two large, all-comer registries of bifurcations treatment (I-BIGIS and COBIS), used as historical controls.. Among 15,991 patients enrolled in the trial, 22,921 lesions treated at the index and staged procedure were available for analysis and 2,757 of these lesions were bifurcations and 7 were trifurcation lesions. The e-CRF-based MADS classification was achieved in 2,757 of these lesions (100%). 80.3% of bifurcations were treated using a single stent, 18.9% using 2 stents and 0.7% using 3 stents. Overall, the "main across side first" approach (A) was used in 77.4% with the "side branch first" approach (S) being the second most frequently used technique (10.2%). A single stent was used in the majority of the "A" approach (87.9%). A reduction in the use of 2-stent techniques (from 33.9 to 18.9%) was observed between GLOBAL LEADERS and I-BIGIS. The "A" approach was the most frequently used technique in GLOBAL LEADERS, while in COBIS the "S" strategy was most frequently employed.. Application of the MADS classification through an e-CRF was feasible in the largest stent trial today and provided useful information about the trends observed overtime in the treatment of bifurcation lesions.

Topics: Antithrombins; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Drug-Eluting Stents; Feasibility Studies; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Predictive Value of Tests; Prosthesis Design; Randomized Controlled Trials as Topic; Recombinant Proteins; Sirolimus; Terminology as Topic; Treatment Outcome

Patients with end-stage renal disease undergoing percutaneous coronary intervention (PCI) have largely been excluded from trials of antithrombotic therapies leaving little data to guide agent choice in this population.. The National Cardiovascular Data Registry CathPCI Registry was used to identify patients with end-stage renal disease undergoing PCI who received monotherapy with either bivalirudin or unfractionated heparin (UFH) (n=71 675). In hospital bleeding and mortality were compared and adjusted using the CathPCI Registry logistic regression models with generalized estimating equations with UFH as the reference. Bivalirudin was used in 51.3% of patients versus 48.7% for UFH. The use of bivalirudin decreased over time, and in 2014, UFH became the most frequently used. Patients receiving UFH were more likely to have an acute coronary syndrome presentation (37.8% versus 27.4%) or have cardiogenic shock (3.74% versus 1.98%). The observed rates for in hospital bleeding (7.0% versus 9.5%; adjusted odds ratio,0.82; 95% confidence interval, 0.76-0.87) and mortality (2.6% versus 4.2%; adjusted odds ratio, 0.87; 95% confidence interval, 0.78-0.97) were lower for patients receiving bivalirudin compared with those receiving UFH.. In patients with end-stage renal disease undergoing PCI, bivalirudin and UFH were used with similar frequency although the patterns of use changed over the enrollment period. Patients with end-stage renal disease undergoing PCI had a lower adjusted risk of in hospital outcomes with bivalirudin; however, given the observational nature of this analysis, a randomized trial is warranted.

Topics: Aged; Anticoagulants; Antithrombins; Coronary Artery Disease; Female; Hemorrhage; Heparin; Hirudins; Hospital Mortality; Humans; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Practice Patterns, Physicians'; Recombinant Proteins; Registries; Risk Factors; Time Factors; Treatment Outcome

We compared the angiographic and clinical outcomes of heparin and bivalirudin in patients who underwent orbital atherectomy for severely calcified coronary lesions.. Severely calcified coronary lesions are associated with increased ischemic complications. Orbital atherectomy modifies calcified plaque, thereby facilitating stent delivery and stent expansion. The ideal antithrombotic agent during orbital atherectomy is unknown. Previous studies reported that bivalirudin was associated with lower bleeding rates compared with heparin plus glycoprotein IIb/IIa inhibitors during percutaneous coronary intervention.. This retrospective multicenter analysis included 458 consecutive real-world patients with severely calcified coronary arteries who underwent orbital atherectomy. Patients were stratified based on the antithrombotic agent that was used. The primary safety endpoint was the 30-day rate of major adverse cardiac and cerebrovascular events, defined as death, myocardial infarction, target-vessel revascularization, and stroke.. Heparin was used in 356/458 cases (77.2%) and bivalirudin was used in 102/458 cases (22.8%). The primary endpoint was similar in the heparin and bivalirudin groups (2% vs 3%; P=.55), as were the 30-day rates of death (1% vs 2%; P=.51), myocardial infarction (1% vs 1%; P=.90), target-vessel revascularization (0% vs 0%; P>.99), and stroke (0% vs 0%; P=.59). Angiographic complication, stent thrombosis, and major bleeding complication rates were similarly low in both groups.. Both heparin and bivalirudin were safe and effective antithrombotic agents for patients who underwent orbital atherectomy. A randomized trial is needed to determine the antithrombotic agent of choice for orbital atherectomy.

Topics: Aged; Aged, 80 and over; Antithrombins; Atherectomy, Coronary; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Dose-Response Relationship, Drug; Female; Fibrinolytic Agents; Heparin; Hirudins; Humans; Male; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Vascular Calcification

The referral of patients for open heart surgery, presenting with a history of heparin hypersensitivity instigated a multidisciplinary effort to find an alternative anticoagulant to heparin. The various options mentioned in the literature call for changes in the routine practice of open heart surgery on cardiopulmonary bypass. These changes involve mostly the perfusion setup and conduct on bypass and to a lesser extent the anesthetic and surgical practice. Nevertheless, the different professions involved in the cardiac surgical firm discussed the proposed changes in a multidisciplinary effort. A new protocol was drafted, endorsed, and executed. The authors highlight these changes and their successful use in the subsequent case study.

Topics: Aged; Algorithms; Anticoagulants; Cardiopulmonary Bypass; Combined Modality Therapy; Coronary Artery Disease; Drug Administration Schedule; Hirudins; Humans; Male; Peptide Fragments; Recombinant Proteins; Thromboembolism; Treatment Outcome

Dialysis patients are at a higher risk of bleeding after percutaneous coronary intervention (PCI); however, due to their exclusion from randomized clinical trials, the optimal antithrombotic regimen for this population remains unknown. We sought to evaluate the comparative safety and effectiveness of bivalirudin monotherapy versus unfractionated heparin (UFH) monotherapy in dialysis patients undergoing PCI.. We included dialysis patients who underwent PCI in a multicenter registry between January 2010 and September 2015 at 47 Michigan hospitals. We compared in-hospital outcomes between bivalirudin versus UFH; excluding those treated with glycoprotein IIb/IIIa inhibitors. Optimal full matching was used to account for the nonrandom use of these drugs.. Of 177,963 patients who underwent PCI, 4,303 (2.4%) were on dialysis. Among those, 1,257 (29.2%) received bivalirudin monotherapy and 2,112 (49.1%) received UFH monotherapy. Patients treated with bivalirudin had fewer comorbidities. After matching, there were no significant differences in outcomes between those who received bivalirudin versus UFH: bleeding (adjusted odds ratio: 0.67; 95% confidence interval: 0.41-1.07; P = 0.093); major bleeding (0.81; 0.19-3.50; P = 0.77); transfusion (1.01; 0.77-1.33; P = 0.96); repeat PCI (0.57; 0.14-2.24; P = 0.42); stent thrombosis (0.56; 0.05-5.83; P = 0.63); and death (0.84; 0.46-1.51; P = 0.55).. We found no significant differences in in-hospital outcomes between bivalirudin and UFH monotherapy among dialysis patients undergoing PCI. Randomized clinical trials are needed to determine the optimal anticoagulant regimen for this population. © 2017 Wiley Periodicals, Inc.

Topics: Aged; Anticoagulants; Antithrombins; Blue Cross Blue Shield Insurance Plans; Comparative Effectiveness Research; Coronary Artery Disease; Female; Hemorrhage; Heparin; Hirudins; Humans; Logistic Models; Male; Michigan; Middle Aged; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Propensity Score; Recombinant Proteins; Registries; Renal Dialysis; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors; Stents; Thrombosis; Time Factors; Treatment Outcome

We aimed to construct a predictive model for one-year mortality in patients undergoing invasive coronary evaluation and to examine the impact of bivalirudin on survival according to the level of baseline risk.. Compared to heparin plus GP IIb/IIIa inhibitors (HEP/GPI), bivalirudin decreases bleeding complications in a range of clinical presentations. The impact of preprocedural risk assessment on survival and whether this is modified by bivalirudin, has not been investigated in detail.. We examined patient-level data from the REPLACE-2, ACUITY, and HORIZONS-AMI trials (n = 18,819) to construct a risk-adjusted mortality model using baseline clinical variables.. One-year mortality occurred in 287 patients (3.1%) assigned to bivalirudin and 336 patients (3.6%) assigned to HEP/GPI (HR 0.85; 95% CI, 0.73-1.00; P = 0.048). Using 11 highly significant predictors of mortality, we developed an integer-risk score to classify patients into risk tertiles. High-risk patients had a rate of 1-year mortality over 9-fold greater than low-risk patients. Consequently, the absolute mortality reduction attributed to bivalirudin was more marked in high-risk patients: 3.1% (-0.8% to 7.0%) in the overall cohort, 4.8% (0.5% to 9.2%) in the PCI cohort (P-interaction versus intermediate and low risk categories, 0.09 and P = 0.02, respectively).. In patients undergoing invasive coronary evaluation, 1-year mortality can be predicted using baseline variables. Bivalirudin treatment (versus HEP/GPI) conferred a survival benefit.

Topics: Aged; Angina, Stable; Angina, Unstable; Anticoagulants; Antithrombins; Coronary Artery Disease; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Proportional Hazards Models; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

The association of bleeding avoidance strategy (BAS) (consisting of a combination of radial access, bivalirudin [rather than heparin +/- glycoprotein GPIIb/IIIa antagonists], and/or vascular closure devices after femoral access) with bleeding and in-hospital outcomes has not been evaluated among elderly patients undergoing percutaneous coronary interventions (PCI).. We studied BAS use, bleeding and in-hospital mortality among 121,635 patients categorized by age (<50, 50-59, 60-69, 70-79, and ≥80years) undergoing PCI from the BMC2 registry (1/2010-12/2013).. The use of BAS decreased marginally with age and despite improved utilization over time, remained lower among the elderly. BAS was used in a much lower risk cohort among all age groups. Nonetheless, compared with no BAS, the use of this strategy was associated with lower bleeding (adjusted OR 0.984, 95% CI 0.980-0.985) and in-hospital mortality (adjusted OR 0.996, 95% CI 0.994-0.997) among all age-groups. Similar relative reduction in the risk of bleeding was observed among all age groups with BAS use with lowest risk (thus greatest absolute risk reduction given their highest risk for bleeding) for the oldest cohort.. BAS use decreased with age among patients undergoing PCI despite its association with lower in-hospital mortality. Although overall utilization improved over time, it still remained lower in the elderly cohort, a group likely to benefit most from it. These data identified an opportunity to design strategies to improve BAS use particularly among high-risk elderly patients undergoing PCI so as to decrease bleeding and reduce related adverse events and costs.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Antithrombins; Blue Cross Blue Shield Insurance Plans; Catheterization, Peripheral; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Female; Femoral Artery; Hemorrhage; Hemostatic Techniques; Hirudins; Hospital Mortality; Humans; Logistic Models; Male; Michigan; Middle Aged; Multivariate Analysis; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Punctures; Recombinant Proteins; Registries; Risk Factors; Time Factors; Treatment Outcome

This study aimed to compare the effect of bivalirudin and unfractionated heparin (UFH) on residual thrombus burden assessed by frequency-domain optical coherence tomography (FD-OCT), and on angiographic indices of microvascular obstruction (MVO).. The efficacy of bivalirudin to inhibit thrombus formation inside the stent during percutaneous coronary interventions (PCI) as compared to UFH is unknown.. Sixty patients with coronary artery disease who underwent post-PCI FD-OCT were studied, including 20 patients treated with bivalirudin and 40 control patients treated with UFH, matched by clinical presentation, stent characteristics, and periprocedural medications. In-stent thrombus volume, thrombus score (number of quadrants with thrombus), and thrombus type (white/red) were assessed by FD-OCT. Thrombolysis in myocardial infarction (TIMI) flow grade, corrected TIMI frame count (cTFC), and Quantitative Blush Evaluator (QuBE) score were recorded.. Patients treated with bivalirudin showed similar thrombus volume (0.14 mm(3) [0.00-0.88] vs. 0.13 mm(3) [0.00-0.63], P = 0.962), thrombus score (10 [0-25] vs. 8 [0-21], P = 0.849) and thrombus length (1.70 mm [0.00-4.10] vs. 1.40 mm [0.00-4.05], P = 0.968], as compared with patients treated with UFH. Patients in the bivalirudin group showed lower proportion of white thrombus (55.5% vs. 78.6%, P = 0.016). There was no significant difference in TIMI flow grade, cTFC, and QuBE score between the two groups.. The present study showed similar residual thrombus burden and angiographic indices of MVO immediately after PCI between patients treated with bivalirudin and those treated with UFH.

Topics: Aged; Controlled Clinical Trials as Topic; Coronary Angiography; Coronary Artery Disease; Coronary Circulation; Coronary Thrombosis; Coronary Vessels; Female; Fibrinolytic Agents; Heparin; Hirudins; Humans; Male; Microcirculation; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Predictive Value of Tests; Recombinant Proteins; Registries; Retrospective Studies; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated reaction in which heparin administration causes a person to enter a pathological and highly prothrombotic state. When patients with known HIT undergo coronary artery bypass and grafting procedures, they must be appropriately anticoagulated. The dangers of heparin administration in this population necessitate the use of an alternative anticoagulant. The case describes the successful use of bivalirudin for procedural anticoagulation during an off-pump coronary artery bypass and grafting.

Topics: Antithrombins; Coronary Artery Bypass, Off-Pump; Coronary Artery Disease; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Recombinant Proteins; Thrombocytopenia

Percutaneous coronary intervention (PCI)-related risks are increased among patients with left main disease (LMD). The aim was to evaluate the impact of antithrombotic therapy on outcomes after LMD PCI in a predominantly ACS population.. One hundred and seventy-seven patients undergoing LMD PCI were identified in a pooled dataset of 14,326 patients from three large randomised trials comparing treatment with heparin plus glycoprotein IIb/IIIa inhibitors (GPI) or bivalirudin alone, including the REPLACE-2, ACUITY and HORIZONS-AMI trials. Overall, net adverse clinical events (NACE) and non-CABG major bleedings at 30 days occurred more frequently in patients undergoing LMD PCI compared to the overall non-LMD PCI population (NACE: 19.8% vs. 10.6%, p≤0.001, major bleeding: 9.6% vs. 4.6%, p≤0.001). In the LMD group, bivalirudin was associated with significantly less non-CABG related major bleeding compared to heparin+GPI (4.5% versus 14.6%, relative risk [RR] 0.27, 95% CI: 0.09-0.83; p=0.013), while the composite ischaemic endpoint (death/MI/TVR) at 30 days was similar in the two groups (11.4% vs. 12.4%, p=0.513) resulting in a benefit on NACE for bivalirudin over heparin+GPI (14.8% vs. 24.7%; RR 0.53; p=0.039).. Among patients undergoing LMD PCI, the use of bivalirudin instead of heparin+GPI resulted in significantly less major bleeding and improved short-term net clinical outcome. Bivalirudin may be the preferred anticoagulation strategy in LMD PCI patients.

Topics: Abciximab; Aged; Aged, 80 and over; Antibodies, Monoclonal; Anticoagulants; Antithrombins; Coronary Artery Disease; Eptifibatide; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; Peptide Fragments; Peptides; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Randomized Controlled Trials as Topic; Recombinant Proteins; Treatment Outcome

The aim of this study was to assess the impact of bleeding after percutaneous coronary intervention (PCI) on the outcome of patients with type 2 diabetes.. This study included 4,329 diabetic patients who underwent PCI. Bleeding was assessed using the Bleeding Academic Research Consortium criteria. The primary outcome was one-year mortality. Bleeding events occurred in 474 patients (10.9%). Access-site and non-access-site bleeds occurred in 274 patients (58%) and 200 patients (42%), respectively. Within the first year after PCI there were 198 deaths: 45 deaths (9.6%) among patients with bleeding and 153 deaths (4.0%) among patients without bleeding (adjusted hazard ratio=2.04 [95% confidence interval 1.38-3.00], p<0.001). There were 25 deaths (12.7%) among patients with non-access-site bleeding and 20 deaths (7.4%) among patients with access-site bleeding (odds ratio [OR]=3.45 [2.20-5.41], p<0.001 for non-access-site bleeding vs. no bleeding and OR=1.90 [1.17-3.01], p=0.008 for access-site bleeding vs. no bleeding). Bleeding improved the discriminatory power of the multivariable model for mortality prediction (p=0.002).. In patients with diabetes undergoing PCI, occurrence of bleeding within the first 30 days after PCI was associated with a significant increase in the risk of one-year mortality.

Topics: Abciximab; Aged; Antibodies, Monoclonal; Anticoagulants; Antithrombins; Aspirin; Clopidogrel; Coronary Artery Disease; Diabetes Mellitus, Type 2; Female; Hemorrhage; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Logistic Models; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prognosis; Proportional Hazards Models; Recombinant Proteins; Risk Factors; Stents; Ticlopidine

After on-pump coronary artery bypass graft surgery, a patient had acute heparin-induced thrombocytopenia with thoracic arterial and venous thrombus formations. Complex emergency surgery with cardiopulmonary bypass and deep hypothermic circulatory arrest using bivalirudin anticoagulation was performed.

Topics: Aged; Anticoagulants; Antithrombins; Blood Coagulation; Cardiopulmonary Bypass; Circulatory Arrest, Deep Hypothermia Induced; Coronary Artery Bypass; Coronary Artery Disease; Dose-Response Relationship, Drug; Heparin; Hirudins; Humans; Male; Peptide Fragments; Recombinant Proteins; Thrombectomy; Thrombocytopenia; Thrombosis

Use of bivalirudin has been associated with a reduction in the incidence of bleeding in patients undergoing percutaneous coronary intervention. Patients with chronic kidney disease, a known predictor of post-percutaneous coronary intervention bleeding, are under-represented in clinical trials.. We evaluated the outcome of 64,052 patients who underwent percutaneous coronary intervention from 2007 to 2009 at 33 hospitals in Michigan and were treated with bivalirudin (28,378) or with heparin and glycoprotein IIb/IIIa inhibitors (35,674). Propensity-matched analysis was adjusted for the nonrandomized use of the 2 strategies. Patients treated with bivalirudin were older, had a lower glomerular filtration rate, and had more comorbidities. Use of bivalirudin was associated with fewer transfusions (2.8% versus 4.2%; P<0.0001), gastrointestinal bleeds (0.5% versus 1.3%; P<0.0001), and vascular complications (1.0% versus 2.5%; P<0.0001), with no difference in survival. Bleeding complications were more common with worsening renal function, but use of bivalirudin was associated with less bleeding across the continuum of renal dysfunction.. The risk of bleeding after percutaneous coronary intervention increases with worsening chronic kidney disease. Bivalirudin was associated with a dramatically reduced risk of bleeding across all categories of renal dysfunction. Our study findings suggest that bivalirudin monotherapy is an acceptable, if not the more appropriate alternative, to heparin and glycoprotein IIb/IIIa inhibitors in patients with chronic kidney disease.

Topics: Aged; Antithrombins; Blue Cross Blue Shield Insurance Plans; Comorbidity; Coronary Artery Disease; Female; Hemorrhage; Hirudins; Humans; Incidence; Kidney; Male; Michigan; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors; Severity of Illness Index; Treatment Outcome

The majority of coronary angioplasty is done via the femoral artery, with vascular complications being a major adverse event. Bivalirudin has been shown to reduce bleeding complication and improve outcomes. The use of bivalirudin in radial interventions has largely been limited due to the routine use of heparin for the diagnostic procedure. In current practice there is a concern with using the traditional 5,000 Units of heparin during radial sheath insertion and administration of bivalirudin when proceeding to percutaneous coronary intervention (PCI). We describe outcome analysis of the use of low-dose heparin (2,500 Units) with bivalirudin in patients who underwent PCI comparing the adverse outcomes related to bleeding and radial artery occlusion.. The study was an institutional review board-approved retrospective analysis of patients who underwent coronary intervention using the radial approach and the use of bivalirudin over 9-month period. Patients on heparin/low-molecular-weight heparin (LMWH), acute myocardial infarction or allergy to bivalirudin were excluded from the study.. We evaluated 155 patients in the radial and 100 patients in the femoral group. The mean age of the population was 63 ± 11 years (males 68%, weight 88 ± 18 kg) and 66 ± 12 years (males 56%, weight 82 ± 16 kg) in the radial and femoral groups, respectively. Ninety-two percent of the radial and 98% of the femoral cases were elective. The vessels intervened upon were similar in the two groups (left main: 0.65% vs. 2%, left anterior descending artery: 39% vs. 38%, diagonal: 3.8% vs.7%, left circumflex: 16% vs. 21%, obtuse marginal: 7 vs. 11%, right coronary artery: 30% vs.31%, grafts: 1% vs. 5%, in the radial and femoral groups, respectively; p > 0.05). The mean activated clotting time at the end of infusion was 376 ± 47 seconds in the radial and 331 ± 18 seconds in the femoral group. There was only 1 case of documented radial artery occlusion that resolved with 2 weeks of LMWH. Six patients in the radial group and 5 in the femoral group reported minor bruising. There were no reported events related to any major bleeding or transfusions.. Bivalirudin in combination with low-dose heparin (2,500 Units) is safe to use in patients undergoing radial angioplasty with similar event rates to the femoral approach.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Coronary Artery Disease; Dose-Response Relationship, Drug; Feasibility Studies; Female; Femoral Artery; Hemorrhage; Heparin; Hirudins; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Radial Artery; Recombinant Proteins; Retrospective Studies; Risk Factors

Topics: Angioplasty, Balloon, Coronary; Antithrombins; Cardiac Catheterization; Coronary Artery Disease; Hemorrhage; Hirudins; Humans; Incidence; Outcome Assessment, Health Care; Peptide Fragments; Radial Artery; Recombinant Proteins

This study sought to develop a risk score predictive of bleeding in patients undergoing percutaneous coronary intervention (PCI) and to investigate the impact of bleeding on subsequent mortality.. Bleeding complications after PCI have been independently associated with early and late mortality.. This study represents a patient-level pooled analysis including 17,034 patients undergoing PCI from 3 large, randomized trials of bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitors, including the REPLACE-2 (Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events), ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy), and HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trials. We developed a risk score to predict noncoronary artery bypass graft (CABG)-related TIMI (Thrombolysis In Myocardial Infarction) major bleeding and evaluated the impact of various types of bleeding on 1-year mortality.. A non-CABG-related TIMI major bleed occurred within 30 days in 267 patients (1.6%), and death occurred in 497 patients (2.9%) within 1 year. A risk score was developed to predict the bleeding risk of patients undergoing PCI, consisting of 7 variables (serum creatinine, age, sex, presentation, white blood cell count, cigarette smoking, and randomized treatment). The TIMI major bleeding rates increased by bleeding risk score groups: from 0.4% for those in the lowest to 5.8% for those in the highest risk group. Non-CABG-related TIMI major bleeding and the occurrence of myocardial infarction within 30 days were independent predictors of subsequent mortality, with respective hazard ratios of 4.2 and 2.9, each p < 0.001. Ranked in order of severity, TIMI major bleeding, blood transfusion without TIMI bleed, TIMI minor bleeding requiring blood transfusion, and TIMI minor bleeding not requiring blood transfusion were independent predictors of subsequent mortality with hazard ratios of 4.89, 2.91, 2.73, and 1.66, respectively. Isolated hematomas were not predictive of subsequent mortality.. Non-CABG-related bleeding within 30 days is strongly associated with an increased risk of subsequent mortality at 1 year in patients undergoing PCI for all indications. A risk score was established to calculate the bleeding risk for patients undergoing PCI, allowing therapeutic decision making to minimize the incidence of bleeding.

Topics: Aged; Angioplasty, Balloon, Coronary; Antithrombins; Confidence Intervals; Coronary Artery Disease; Drug-Eluting Stents; Female; Health Status Indicators; Hemorrhage; Heparin; Hirudins; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Myocardial Reperfusion; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Assessment; Risk Factors; Triage

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

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Artery Disease; Diabetes Complications; Hemorrhage; Heparin; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Risk Factors; Stroke

This study sought to evaluate the short- and long-term efficacy and safety of bivalirudin in diabetic patients undergoing percutaneous coronary intervention (PCI) in contemporary clinical practice.. Early trials of platelet glycoprotein (GP) IIb/IIIa inhibitors have suggested a survival benefit in diabetic patients undergoing PCI. More recently, randomized trials have demonstrated that diabetic patients have similar protection from acute ischemic events, while lowering the risk of bleeding complications, when treated with bivalirudin monotherapy versus heparin plus GP IIb/IIIa blockade. However, the impact of bivalirudin use on long-term outcomes in diabetic patients undergoing PCI remains unclear.. Using the Cornell Angioplasty Registry, we studied 786 consecutive diabetic patients undergoing urgent or elective PCI with a mean clinical follow up of 24.6 +/- 7.8 months. Of these, 428 patients (54.5%) received bivalirudin monotherapy and 358 patients (45.5%) received unfractionated heparin (UFH) plus GP IIb/IIIa inhibition. The incidence of in-hospital death (0% vs. 0.3%; p = 0.46), post-procedural myocardial infarction (MI) (4.7% vs. 7.0%; p = 0.169), and major adverse cardiovascular events (MACE) (death, MI, stroke or urgent revascularization) (4.9% vs. 7.3%; p = 0.176) was similar in the two groups, with less minor bleeding (9.6% vs. 14.5%; p = 0.035) in the bivalirudin vs. UFH plus GP IIb/IIIa inhibitor group, respectively. By the end of follow up, there were 38 (8.9%) deaths in the bivalirudin vs. 19 (5.3%) deaths in the GP IIb/IIIa inhibitor arm (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.0-3.1; p = 0.04). However, after a propensity score-adjusted multivariate Cox regression analysis, there was no longer a significant difference in long-term mortality between the two groups (HR 1.63; chi(2) = 2.61; 95% CI 0.90-2.94; p = 0.106).. These findings indicate that in diabetic patients, bivalirudin monotherapy results in similar protection from acute ischemic events and long-term mortality, while lowering the risk of minor bleeding in comparison to UFH plus GP IIb/IIIa inhibition.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Artery Disease; Diabetes Complications; Female; Follow-Up Studies; Heparin; Hirudins; Humans; Infusions, Intravenous; Logistic Models; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Registries; Retrospective Studies; Stroke; Treatment Outcome

A patient with impaired left ventricular function was scheduled for coronary artery bypass grafting. The patient's history revealed a life-threatening allergy to fish proteins. Therefore, because of the threat of cross-reactivity to protamine, a standard anticoagulation protocol with heparin/protamine was disapproved. Instead, complete coronary artery revascularization was successfully performed off-pump using bivalirudin as the anticoagulant.

Topics: Anaphylaxis; Anticoagulants; Coronary Artery Bypass, Off-Pump; Coronary Artery Disease; Drug Hypersensitivity; Heparin Antagonists; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Protamines; Recombinant Proteins

Although bivalirudin use in percutaneous coronary intervention (PCI) results in less bleeding compared to unfractionated heparin (UFH) use, its safety in patients undergoing rotational atherectomy (RA) is unknown.. A cohort of 503 patients who underwent PCI with RA from 2000 to 2009 was studied. Patients receiving bivalirudin (n = 322) were compared to those (n = 181) treated with UFH +/- glycoprotein IIb/IIIa inhibitor (GPI) as PCI anticoagulation. Safety was assessed by the frequency of major bleeding (hematocrit drop > or =15%, intracerebral or gastro-intestinal bleeding) and need for transfusion. Efficacy was assessed by a composite end-point of in-hospital death, Q wave myocardial infarction (MI) or urgent coronary artery bypass graft (CABG).. Those in the bivalirudin group were older, more hypertensive, and had greater body mass index. The UFH group was more likely to have prior MI, prior CABG, and an acute coronary syndrome at baseline. GPI was used in 93 patients (52%) of the UFH group. No difference was found between groups for the composite of death/Q wave MI/urgent CABG (1.9% vs. 1.7%, respectively, in bivalirudin vs. UFH group; P = 0.2). The frequency of major bleeding (2.2% vs. 1.7%; P = 0.8) or transfusion (5.6% vs. 8.7%; P = 0.9) was also similar between groups. After adjustment, bivalirudin use was not associated with a reduction in death/Q wave MI/urgent CABG, major bleeding, or transfusion compared to UFH.. Bivalirudin use seems to be as safe and effective as UFH in patients undergoing RA.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Atherectomy, Coronary; Body Mass Index; Cohort Studies; Confidence Intervals; Coronary Artery Disease; District of Columbia; Female; Gastrointestinal Hemorrhage; Hematocrit; Heparin; Hirudins; Humans; Intracranial Hemorrhages; Male; Multivariate Analysis; Odds Ratio; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Propensity Score; Recombinant Proteins; Registries; Retrospective Studies; Risk Factors; Stents

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Atherectomy, Coronary; Coronary Artery Disease; District of Columbia; Gastrointestinal Hemorrhage; Heparin; Hirudins; Humans; Intracranial Hemorrhages; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Treatment Outcome

Bivalirudin, a DTI, has evolved from relative obscurity as an anticoagulation option in patients resistant to or allergic to either LMWH or UFH to a commonly used, safe alternative. Most of the early studies comparing bivalirudin to UFH with or without a GP IIb/IIIa agent had composite endpoints (death, MI, bleeding) whose statistical significance were driven exclusively by a significant reduction in bleeding. Newer studies now demonstrate reductions in mortality, which has led to a paradigm shift in anticoagulant choice both in elective and emergent coronary procedures. We present the major studies that have brought bivalirudin to the forefront of coronary artery disease, specifically coronary interventional procedures.

Topics: Anticoagulants; Clinical Trials as Topic; Coronary Artery Disease; Hirudins; Humans; Peptide Fragments; Recombinant Proteins

The use of glycoprotein IIb/IIIa inhibitors (GPI) reduces ischemic events in patients undergoing percutaneous coronary intervention (PCI). However, the same properties that confer this benefit lead to an increased bleeding risk. Recent studies have shown a less robust net clinical benefit of GPI in the current era of routine thienopyridine and direct thrombin inhibitor use. To optimize the net clinical benefit of GPI, these agents need to be selectively used in patients most likely to benefit from their anti-ischemic effect, namely patients undergoing PCI for non-ST-segment elevation myocardial infarction, select patients undergoing primary PCI, and select patients undergoing PCI without appropriate pre-loading with a thienopyridine. Moreover, strategies to minimize bleeding should be applied in these patients and include shorter GPI infusions (in some patients), dose adjustments of heparin and GPI, careful access site management with more frequent use of the transradial approach, use of smaller sheaths, and identification of patients at high bleeding risk. This review provides an update of the current literature that supports these measures, an insight on the tailored use of GPI, and a potential direction for future research addressing combined antithrombotic therapies.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Coronary Artery Disease; Eptifibatide; Hemorrhage; Hirudins; Humans; Peptide Fragments; Peptides; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Risk Assessment; Risk Factors; Treatment Outcome

Platelets are activated in vivo by multiple agonists; however, platelet function testing in vitro has been performed predominantly with only one or two agonists of platelet activation. Greater insight into anticipated effects of antithrombotic regimens should enhance the design of successful clinical trials. To test this concept, we assessed platelet activation induced by multiple agonists and two antithrombotic regimens, unfractionated heparin (UFH) and eptifibatide compared with bivalirudin and cangrelor. Blood samples from 10 patients with coronary artery disease were spiked with pharmacologic concentrations achieved in vivo of either UFH (1.2 U/ml) and eptifibatide (1.7 microg/ml), or with bivalirudin (8 microg/ml) and cangrelor (500 nmol/l). Platelet function was assessed with the use of flow cytometry. Agonists included thrombin (50 nmol/l), adenosine diphosphate (1 micromol/l), the collagen-mimetic convulxin (5 ng/ml), and platelet-activating factor (10 nmol/l). When platelet activation was identified by the surface expression of P-selectin in response to multiple agonists, the combination of bivalirudin and cangrelor suppressed activation more than UFH and eptifibatide. When platelet activation was identified by the activation of glycoprotein IIb-IIIa (PAC-1 binding), the combination of bivalirudin and cangrelor was more effective in suppressing activation in response to thrombin and adenosine diphosphate, whereas UFH and eptifibatide more effectively prevented binding of PAC-1 when platelets were activated with the collagen-mimetic convulxin. In conclusion, bivalirudin and cangrelor suppressed platelet activation in response to diverse agonists in vitro more than UFH and eptifibatide. These results and this approach to selection of promising interventions should be helpful in streamlining the design of clinical trials.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Animals; Blood Platelets; Clinical Trials as Topic; Coronary Artery Disease; Crotalid Venoms; Drug Evaluation, Preclinical; Drug Therapy, Combination; Eptifibatide; Fibrinolytic Agents; Flow Cytometry; Heparin; Hirudins; Humans; Lectins, C-Type; P-Selectin; Peptide Fragments; Peptides; Pilot Projects; Platelet Activating Factor; Platelet Activation; Platelet Function Tests; Recombinant Proteins; Research Design; Thrombin

With an aging population, nonagenarians constitute an increasing percentage of patients with coronary artery disease. The aim of this study was to determine the predictors and outcome of nonagenarians undergoing percutaneous coronary intervention (PCI) for symptomatic coronary artery disease.. From 2002 to 2007, a cohort of 171 consecutive nonagenarians underwent PCI and stent implantation in our center. Patients given bivalirudin (n = 79) during the procedure were compared to those given heparin (n = 92). In-hospital and 6-month rates of major adverse cardiovascular events (MACE) including death, myocardial infarction (MI), and target lesion revascularization were indexed. In-hospital bleedings were also indexed.. The mean age was 92.5 +/- 2.5 years. The population was 52% female. Nearly 30% of patients had diabetes mellitus and >25% had renal failure. The mean left ventricular ejection fraction was 45%+/- 14%. The clinical presentation was an acute MI in 59% of the cases. The in-hospital rates of death and bleedings were 4.1% and 17.5%, respectively. Clinical presentations as MI or cardiogenic shock were associated with high rates of in-hospital death: 19.3% and 30%, respectively. Bivalirudin use was associated with a 41.5% decrease in in-hospital bleedings. The 6-month incidence of MACE was 13.6% and was driven by death. Predictors of 6-month outcomes were clinical presentations as MI or cardiogenic shock, renal failure, and total stent length.. Nonagenarians represent a particular population with a high percentage of females and a high incidence of comorbidities. In this study, we highlighted that nonagenarians have logically a worse prognosis than is reported in younger patients, with especially high rates of in-hospital bleedings. Bivalirudin use was associated with an important decrease in in-hospital bleedings; thus, it should be systematically considered in such patients to improve early outcome.

Topics: Aged, 80 and over; Anticoagulants; Cohort Studies; Comorbidity; Coronary Artery Disease; Female; Heparin; Hirudins; Hospital Mortality; Humans; Male; Peptide Fragments; Proportional Hazards Models; Recombinant Proteins; Stents; Treatment Outcome

We report a combined carotid endarterectomy and coronary revascularization surgery with cardiopulmonary bypass using bivalirudin for systemic anticoagulation in a patient with a positive titer for the heparin-platelet factor 4 antibody. The patient experienced procedural success for both the carotid and coronary surgeries. Increased blood and blood product transfusion was required postoperatively.

Topics: Anticoagulants; Autoantibodies; Blood Coagulation; Cardiopulmonary Bypass; Carotid Stenosis; Coronary Artery Bypass; Coronary Artery Disease; Endarterectomy, Carotid; Heparin; Hirudins; Humans; Intraoperative Care; Male; Middle Aged; Peptide Fragments; Platelet Factor 4; Recombinant Proteins; Thrombocytopenia; Treatment Outcome

This study aimed to analyze the impact of replacing heparin with bivalirudin in octogenarians undergoing percutaneous coronary intervention (PCI) on postprocedure hemorrhage and 6-month mortality.. Randomized trials comparing the antithrombin agent bivalirudin with heparin as the intraprocedural anticoagulant identify a reduction in periprocedural bleeding after PCI. Further, the occurrence of such bleeding seems to predict an increased risk of death or myocardial infarction both in-hospital and at long-term follow-up. Importantly, elderly people who are at the greatest risk of post-PCI bleeding complications are underrepresented in these randomized trials.. From 2000 to 2007, 2,766 consecutive patients from our center who were > or = 80 years of age underwent PCI with stent implantation and were included in this analysis. Bivalirudin was used in 1,207 (43.6%) patients and heparin in 1,559 (56.4%). We compared the rates of post-PCI bleeding complications and 6-month mortality.. The overall in-hospital bleeding and 6-month mortality rates were 4.6% and 11.8%, respectively. By multivariate logistic regression and after adjustment by propensity score analysis, bivalirudin was associated with a significant decrease in in-hospital bleedings (HR = 0.41, 95% CI = 0.23-0.73, P = 0.003). By multivariate Cox analysis, bivalirudin was also associated with a significant decrease (HR = 0.6, 95% CI = 0.4-0.9, P = 0.01) and in-hospital bleedings with a significant increase in the 6-month mortality (HR = 2.5, 95% CI = 1.6-3.9, P < 0.001).. This study suggests an important subset for use of bivalirudin in lieu of heparin that will benefit the very elderly.

Topics: Age Factors; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Angiography; Coronary Artery Disease; Female; Hemorrhage; Heparin; Hirudins; Humans; Kaplan-Meier Estimate; Logistic Models; Male; Patient Selection; Peptide Fragments; Proportional Hazards Models; Recombinant Proteins; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Stents; Time Factors; Treatment Outcome

The objective of this study is to analyze the clinical outcomes and treatment strategies of coronary wire perforations (WPs) in the era of heparin use compared to the era of bivalirudin use.. Percutaneous coronary intervention (PCI) advances have led to progressive decrease in complications. Therefore, complex coronary lesions such as chronic total occlusions and calcified lesions are being attempted with stiff/hydrophilic wires with resultant higher incidence of coronary WP.. A single-center retrospective data analysis of coronary perforation (CP) for the last 4 years with review of coronary angiograms was done and WPs were identified. A simple classification scheme based on angiographic appearance of CP was made: Type I ("myocardial stain," with no frank dye extravasation) and type II ("myocardial fan," with dye extravasation to pericardial cavity or cardiac chambers).. Overall incidence of CP was 0.49% (82/16,859). Of these 50 (61%) were caused by WP; 30 occurred with heparin use (Group A) and 20 with bivalirudin use (Group B). WPs always occurred in type B2/C lesions (100%) and commonly with use of hydrophilic guidewires (70%). Major adverse cardiac events and cardiac tamponade were frequent in group A (50%) and none in group B (0%); P < 0.01. All WP in group B responded to stopping anticoagulation and prolonged balloon inflation, while group A type II perforations frequently required additional interventions (pericardiocentesis, coil embolization).. Cardiac tamponade and major adverse cardiac events from WPs were less frequent with bivalirudin use compared to heparin use. This beneficial effect of bivalirudin may be explained on the basis of its short half-life and reversible thrombin inhibition property. Therefore, bivalirudin may offer a safer alternative for anticoagulation in complex PCI.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Balloon Occlusion; Cardiac Tamponade; Cineangiography; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Female; Heparin; Heparin Antagonists; Hirudins; Hospital Mortality; Humans; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Pericardiocentesis; Recombinant Proteins; Registries; Retrospective Studies; Treatment Outcome; Wounds, Penetrating

Simultaneous integrated coronary artery revascularization combines coronary artery bypass surgery and percutaneous coronary intervention into a single procedure. This approach provides immediate, complete and optimal myocardial revascularization in a less invasive manner. Because simultaneous integrated coronary revascularization necessitates two distinct anticoagulation protocols for the surgical and percutaneous aspects of the procedure, combining these anticoagulation protocols carries a bleeding risk. Using a single anticoagulant to facilitate the necessities of both aspects of the integrated approach may alleviate this risk.. A 45-year-old man with an occluded left anterior descending artery and a moderately stenotic circumflex artery underwent simultaneous integrated coronary revascularization. Bivalirudin was used to achieve anticoagulation for the duration of the procedure. The patient was asymptomatic with excellent patency of both the bypass graft and the stented circumflex artery via angiography at 10 months.. Bivalirudin can be used to effectively achieve a unified anticoagulation protocol for simultaneous integrated revascularization.

Topics: Anticoagulants; Coronary Artery Disease; Coronary Vessels; Hirudins; Humans; Male; Middle Aged; Myocardial Revascularization; Peptide Fragments; Recombinant Proteins

Topics: Age Factors; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Angiography; Coronary Artery Disease; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Risk Assessment; Risk Factors; Stents; Time Factors; Treatment Outcome

Patients on dialysis constitute a major healthcare burden with high prevalence of coronary artery disease frequently requiring coronary revascularization. Prior studies have reported high complications rates with revascularization in patients on dialysis. However, information on the use glycoprotein and direct thrombin inhibitors in this patient population undergoing percutaneous revascularization is limited. We retrospectively analyzed the procedural success and in-hospital outcomes of percutaneous coronary revascularization in 56 consecutive patients on dialysis compared with 524 patients without renal failure, between January 2001 and August 2007 at our facility. Additionally, we also analyzed the off-label use of glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors during revascularization in this high-risk group of patients to evaluate for possible increased bleeding complications. In the study group, 7 interventions were performed on peritoneal dialysis and 49 on hemodialysis patients. Sixty-one percent of these patients had diabetes mellitus. A total of 72 lesions were intervened upon; 12 underwent angioplasty and 60 underwent stenting. Four of 72 interventions were not successful, giving a procedural success rate of 94%. There were 6 immediate complications (10.7%), but no deaths. Thirty-two patients (57%) received GP IIb/IIIa inhibitors while direct thrombin inhibitors were used during percutaneous coronary intervention in 11(20%) patients. There were no bleeding complications with use of either GP IIb/IIIa inhibitors or direct thrombin inhibitors. In our experience, percutaneous coronary intervention has high procedural success in dialysis patients and concomitant use of GP IIb/IIIa inhibitors is not associated with any major bleeding complications, making this a feasible, safe and effective revascularization option for patients on dialysis; however, this merits further study in a randomized prospective trial.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Combined Modality Therapy; Coronary Artery Disease; Female; Hirudins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Risk Factors; Treatment Outcome

Maintaining a therapeutic level of anticoagulation with unfractionated heparin remains a major challenge for clinicians because of the wide variability of patient responses, which may be explained by variable binding of heparin to plasma proteins. Direct thrombin inhibitors may offer an advantage in more predictable anticoagulation.. Plasma samples from normal volunteers, stable coronary artery disease (CAD) patients, unstable angina patients, and acute myocardial infarction patients were obtained. A fixed concentration of heparin (.13 U/ml) or bivalirudin (1.6 microg/ml) was added to plasma from each of the four study groups and measurement of the APTT was performed. In addition, a pool of plasma from patients with acute MI was diluted in pooled normal plasma, and heparin or bivalirudin was added to the plasma preparation and APTT measurements performed.. In heparin-treated plasma samples, mean APTT values were 443 +/- 137% baseline for normal volunteers, 347 +/- 116% for patients with stable CAD, 290 +/- 124% for patients with unstable angina (p < 0.05), and 230 +/- 120% for patients with acute MI (p < 0.05). APTT did not differ across the four groups treated with bivalirudin. There was a much higher degree of variability in APTT values in heparin treated controls (272%-671%, SD approximately 30%) compared to bivalirudin treated controls (284-499%, SD approximately 12%). When the "acute MI pool" was diluted in pooled normal plasma at fixed concentrations of either bivalirudin (1.6 mug/ml) or heparin (0.13 U/ml), there was a sharp decrease in heparin activity from 407% baseline (at 0% acute MI pool) to values as low as 126% baseline (at 100% acute MI pool). A markedly different pattern was seen in the bivalirudin treated samples, where a trend towards decreased APTT values was seen only at the 100% acute MI pool.. Both heparin variability and resistance may limit optimal antithrombotic therapy with heparin in patients with ACS and constitutes a potential advantage of direct antithrombin blockade with bivalirudin.

Topics: Aged; Angina, Unstable; Anticoagulants; Case-Control Studies; Coronary Artery Disease; Drug Resistance; Female; Heparin; Hirudins; Humans; In Vitro Techniques; Male; Middle Aged; Myocardial Infarction; Partial Thromboplastin Time; Peptide Fragments; Recombinant Proteins

The use of bivalirudin in percutaneous coronary interventions has been shown to be clinically safe and effective, and may be associated with shorter hospital stays and lower costs than heparin + glycoprotein (GP) IIb/IIIa inhibition. This study compared the utilization, clinical outcomes and costs associated with the planned use of bivalirudin versus heparin + GP IIb/IIIa inhibition in drug-eluting stent (DES) patients without acute myocardial infarction (MI).. We retrospectively studied 1,842 patients who underwent DES placement between May 2003 and December 2004. Planned treatment with heparin + GP IIb/IIIa inhibition was administered to 1,305 and planned bivalirudin alone was administered to 537 patients. Clinical follow ups (mean = 782 +/- 204 days) were obtained via telephone or mailed surveys in 1,813 patients (98.4%). Propensity analysis was utilized to adjust for between-groups baseline differences.. The unadjusted data revealed similar in-hospital outcomes in both groups. After propensity adjustment, the rate of vascular complications was significantly lower in the bivalirudin-treated group (0.2% vs. 1.2%; p = 0.04). At 1 year, clinical outcomes were similar in both groups. The overall unadjusted and adjusted cost analysis revealed similar mean hospital costs (11,384 U.S. dollars vs. 11,018 U.S. dollars; p = ns) and length of stay (2.9 days vs. 2.8 days; p = ns) in both groups. The unadjusted and adjusted mean hospital costs were significantly lower in patients treated with bivalirudin versus patients who received heparin + abciximab.. These observations suggest that bivalirudin is a safe, cost-effective alternative to heparin + GP IIb/IIIa inhibition in patients undergoing DES in the absence of acute MI.

Topics: Abciximab; Aged; Antibodies, Monoclonal; Anticoagulants; Coronary Artery Disease; Costs and Cost Analysis; Drug Delivery Systems; Drug Therapy, Combination; Eptifibatide; Female; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Immunosuppressive Agents; Length of Stay; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Peptide Fragments; Peptides; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Retrospective Studies; Sirolimus; Stents; Tirofiban; Treatment Outcome; Tyrosine

Topics: Anticoagulants; Coronary Artery Disease; Costs and Cost Analysis; Drug Delivery Systems; Heparin; Hirudins; Humans; Immunosuppressive Agents; Length of Stay; Myocardial Infarction; Paclitaxel; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Sirolimus; Stents

The use of heparin in patients with heparin-induced thrombocytopenia (HIT) may result in severe complications or death. The diagnosis of HIT is frequently uncertain, however. Alternative anticoagulants in at-risk patients undergoing cardiac surgery with cardiopulmonary bypass remain problematic. The novel short-acting, direct-thrombin inhibitor bivalirudin is the only alternative to heparin/protamine being used in elective non-HIT patients during CPB.. Four patients with severe thrombocytopenia after heparin exposure and suspected acute HIT underwent on-pump coronary artery bypass grafting surgery with preemptive use of bivalirudin. A continuous bivalirudin infusion was used during cardiopulmonary bypass, and activated clotting times were used to monitor anticoagulation.. Anticoagulation with bivalirudin during cardiopulmonary bypass was effective and uncomplicated. Duration of operation was not prolonged, and perioperative blood loss and transfusion rates were acceptable. Activated clotting times were helpful for monitoring anticoagulation in these patients.. These data provide further evidence of the feasibility of bivalirudin for anticoagulation during on-pump coronary artery bypass graft surgery in urgent clinical situations.

Topics: Aged; Anticoagulants; Coronary Artery Bypass; Coronary Artery Disease; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Recombinant Proteins; Thrombocytopenia

Topics: Aged; Anticoagulants; Coronary Artery Bypass; Coronary Artery Disease; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Recombinant Proteins; Thrombocytopenia

This article presents the case of a patient with severe haemophilia A who underwent successful multivessel percutaneous coronary intervention (PCI). Patients with haemophilia who are diagnosed with coronary artery disease (CAD) and require intervention present a challenge to doctors due to the high risks of bleeding. The patient was administered recombinant factor VIII pre- and post-procedure. Anticoagulation during PCI was maintained with bivalirudin, a thrombin-specific anticoagulant. There were no complications and the patient tolerated the procedure well. This case suggests that bivalirudin as the sole procedural anticoagulant can be safely used in patients with a very high risk of bleeding undergoing PCI.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Angiography; Coronary Artery Disease; Hemophilia A; Hirudins; Humans; Intraoperative Care; Male; Middle Aged; Peptide Fragments; Recombinant Proteins; Treatment Outcome

Anticoagulation during percutaneous coronary intervention (PCI) requires the monitoring of activated clotting time (ACT) to protect from periprocedural ischemic and bleeding complications; however, the optimal ACT values have not been established when PCI is performed with bivalirudin. After 495 consecutive patients treated for coronary artery disease with PCI received bivalirudin as a single anticoagulation agent, it was found that ACT is reproducible when bivalirudin is used during PCI and does not correlate with clinical events.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Chi-Square Distribution; Coronary Artery Disease; Female; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Recombinant Proteins; Reproducibility of Results; Retrospective Studies; Whole Blood Coagulation Time

Platelet reactivity predicts complications after percutaneous coronary intervention (PCI). Accordingly, agents that suppress platelet reactivity should decrease adverse events after PCI. This study was designed to determine the effects of therapeutic concentrations of unfractionated heparin (UFH), bivalirudin, or enoxaparin alone or in combination with tirofiban on platelet reactivity.. Blood taken from 13 patients with coronary artery disease was exposed to each anticoagulant alone or in combination with tirofiban ex vivo. Platelet reactivity was characterized with flow cytometry to quantify the percentage of platelets capable of binding fibrinogen (activation of glycoprotein IIb-IIIa) and expressing P-selectin in response to adenosine diphosphate (ADP, 0, 0.2, and 1 microM).. Platelet reactivity was greater in blood treated with UFH than in blood anticoagulated with bivalirudin with respect to both the capacity to bind fibrinogen (by 4 +/- 1.8%, p = 0.01) and P-selectin expression (by 7.7 +/- 0.7%, p, < 0.0001) in response to 1 microM ADP. Platelet reactivity was greater in blood treated with UFH than in blood exposed to enoxaparin with respect to P-selectin expression (by 7 +/- 1.1%, p, < 0.0001) in response to 1 microM ADP. Platelet reactivity was similar in blood treated with bivalirudin or enoxaparin. Addition of tirofiban suppressed the capacity to bind fibrinogen in the presence of each anticoagulant to a similar extent.. As platelet reactivity is greater in blood anticoagulated with UFH in comparison with blood anticoagulated with enoxaparin or bivalirudin, the use of bivalirudin or enoxaparin rather than UFH during PCI should contribute to a reduced incidence of adverse cardiac events after PCI.

Topics: Adenosine Diphosphate; Aged; Anticoagulants; Coronary Artery Disease; Drug Evaluation; Enoxaparin; Flow Cytometry; Heparin; Hirudins; Humans; Middle Aged; P-Selectin; Peptide Fragments; Platelet Activation; Platelet Function Tests; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins