Bivalirudin In Percutaneous Coronary Intervention Research Articles

Evaluation of the Safety and Efficacy of Bivalirudin Anticoagulation in Patients with Heparin-Induced Thrombocytopenia According to Renal Function and Body Mass Index

Background: Heparin-induced thrombocytopenia (HIT) is a life-threatening complication in which antibodies to platelet factor 4 complexed to heparin lead to platelet overactivation resulting in a hypercoagulable state. Treatment begins with stopping all sources of heparin and initiating rapid-acting non-heparin anticoagulation. Bivalirudin is a direct thrombin inhibitor (DTI) used off-label for the prevention and treatment of HIT. It is primarily enzymatically cleared; however, dose reductions are required in renal impairment. Despite its widespread off-label use in HIT, there is a paucity of data for dosing bivalirudin in patients with renal dysfunction and obesity. Here we report the results of a medication use evaluation (MUE) investigating the safety and efficacy of dosing bivalirudin based on renal function and body mass index (BMI). Methods: We conducted a retrospective MUE including patients 18-89 years of age receiving bivalirudin with ≥3 DTI levels between June 2019 and December 2021. Patients receiving bivalirudin for percutaneous coronary intervention were excluded. Creatinine clearance was measured with the Cockcroft-Gault equation. The primary outcome was time to therapeutic anticoagulation (TTA) defined as the time in hours (hr) between bivalirudin initiation and the first of two consecutive therapeutic DTI levels. Secondary outcomes included average initial therapeutic dose, time in therapeutic range (TTR) calculated as the percentage of therapeutic DTI levels, incidence of clinically significant bleeding, and average number of dose changes before reaching therapeutic goal. Results: Thirty-eight patients (21 females, 55%) with a mean (SD) age of 60.3 (13.5) years were included, 12 of which had a history of or confirmed HIT by serotonin release assay. The remaining patients had suspected HIT or coagulation abnormalities precluding the use of heparin. One patient was classified as an outlier and excluded due to requiring an abnormal number of dose adjustments. Among this population, 17 (45%) had normal renal function (CrCl >60 mL/min), 11 (29%) had mild renal impairment (CrCl 30-60 mL/min), 1 (3%) had moderate renal impairment (CrCl <30 mL/min), 4 (10%) were on intermittent hemodialysis (IHD), and 5 (13%) were on continuous renal replacement therapy (CRRT). Stratified by BMI, 2 (5%) were underweight (BMI <18.5 kg/m2), 3 (8%) were healthy (BMI 18.5-24.9 kg/m2), 17 (45%) were overweight (BMI 25.0-29.9 kg/m2), and 16 (42%) were obese (BMI ≥30 kg/m2). There was no statistically significant difference in TTA based on renal function or BMI. However, clinically, patients on IHD or CRRT trended toward having a shorter TTA compared to patients with normal, mildly impaired, and moderately impaired renal function (28.2 ± 9.0 or 28.9 ± 16.3 hr vs. 40.0 ± 27.6, 36.7 ± 31.6, and 42.9 hr, respectively). Obese and overweight patients trended toward a shorter TTA compared to healthy and underweight patients (31.4 ± 28.9 and 32.8 ± 17.4 hr vs. 62.3 ± 35.6 and 54.8 ± 5.0 hr, respectively). The difference in TTA may be affected by lab turnaround time (TAT). To adjust for lab TAT, the average number of dose adjustments was assessed. There was no difference in the number of dose adjustments based on renal function. In contrast, overweight and obese patients trended toward requiring fewer dose changes compared to underweight and healthy patients. This trend aligned with overweight and obese patients achieving a statistically significantly higher TTR compared to underweight and healthy patients (55.5 vs. 34.4%, p = 0.02). Based on bivalirudin's standard renal dose adjustments, patients with a CrCl >60 mL/min had a statistically significantly larger average initial therapeutic dose compared to those with a CrCl ≤60 mL/min (0.114 vs. 0.069 mg/kg/hr, p < 0.001). However, this difference was not observed based on BMI. Incidences of clinically significant bleeding were not observed to have affected TTA, TTR, average initial therapeutic dose, or number of dose changes before reaching therapeutic anticoagulation. Conclusion: While our data are consistent with bivalirudin requiring renal dose adjustments, it was observed that underweight and healthy BMI patients required more dose adjustments and took longer to achieve therapeutic anticoagulation. More studies are needed to determine if these patients would benefit from a higher initial dosing strategy. This study was limited due to the sample size. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Bivalirudin in patients undergoing percutaneous coronary intervention and independent predictors of postoperative adverse events in these patients: A real world retrospective study.

The efficacy and safety of bivalirudin in percutaneous coronary intervention (PCI) has always been a hot topic in perioperative antithrombotic therapy, but there are still some controversies. So studies are needed to provide more evidence, especially the real world study which includes patients excluded from previous RCT studys. Our study aimed to investigate these information and analyze the independent predictors of postoperative adverse events.A retrospective study enrolled 1416 patients underwent PCI in Tianjin Chest Hospital from May 2016 to October 2017. The incidence of stent-thrombosis and net clinical adverse events, including all-cause death, myocardial infarction, stroke, urgent target-vessel revascularization and bleeding, were followed up for 30 days and 1 year. Logistic regression and COX regression were respectively used to analyze independent predictors of bleeding events within 30-days, and independent predictors of Major adverse cardiovascular and cerebrovascular events (MACCE) in patients with stent implantation within 1-year.Seven hundred six patients were treated with bivalirudin while 710 with unfractionated heparin (UFH). The proportions of diabetes, hypertension, anemia, myocardial-infarction history, PCI history, moderate-to-severe renal-impairment, gastrointestinal-bleeding history in the bivalirudin group were significantly higher (P < .05). Women, anemia were independent risk factors for bleeding within 30-days (P < .05). Among 682 patients with stent implantation in bivalirudin group, anemia, Body Mass Index (BMI) >25 kg/m2, KILLIP ≥2, ejection fraction (EF) <45%, eGFR <60 ml/minutes were independent risk factors for MACCE, while Statins, proton pump inhibitor (PPI) were independent protective factors for MACCE with-in 1-year (P < .05).Bivalirudin have good anticoagulant effect and lower bleeding risk during PCI, especially in patients with higher bleeding risk. In patients treated with bivalirudin, female, anemia were independent predictors of bleeding within 30-days, BMI >25 kg/m2, anemia, KILLIP ≥2, EF <45%, eGFR <60 ml/minutes were independent risk factors and Statins, PPI were independent protective factors of MACCE within 1-year.

Efficacy and safety of bivalirudin for percutaneous coronary intervention in acute coronary syndromes: a meta-analysis of randomized-controlled trials.

The efficacy and safety of bivalirudin in patients undergoing percutaneous coronary intervention (PCI) for treatment of acute coronary syndromes (ACS) remains controversial despite recent evidence from large randomized-controlled trials (RCTs). Thus, this systematic review and meta-analysis sought to investigate the efficacy and safety of bivalirudin as compared to heparin in patients with ACS undergoing PCI. Medline/PubMed, Cochrane Central Register of Controlled Trials, and Clinical Trials.gov databases were searched for RCTs. Primary endpoint was MACE consisting of all-cause death, myocardial infarction, and stroke within 30 days. Secondary endpoints were components of the primary endpoint and stent thrombosis. The primary safety endpoint was major bleeding. We identified 12 RCTs comprising 33,844 patients. Between bivalirudin and heparin, there were no significant differences for MACE (OR 1.06; 95% CI 0.96-1.17; p = 0.24), death, myocardial infarction, and stent thrombosis. Similar results were seen following stratification by use of glycoprotein inhibitors (GPI). Major bleeding trended to be less frequent in patients treated with bivalirudin. However, no safety benefit for bivalirudin was seen when use of GPI was balanced between groups (OR 0.88; 95% CI 0.67-1.16; p = 0.35; p for heterogeneity < 0.01). Compared with heparin, bivalirudin was associated with a similar incidence of ischemic events following PCI for ACS. An association of bivalirudin with decreased bleeding was not seen with balanced use of GPI.

Patients treated with bivalirudin are still at higher risk of stent thrombosis: a comprehensive meta-analysis of randomised clinical trials of bivalirudin and heparin for percutaneous coronary interventions.

Although the current practice guidelines recommend using both heparin and bivalirudin for percutaneous coronary interventions (PCI), the research data are ambiguous. The aim of the study was to compare the impact of bivalirudin and heparin on major clinical endpoints in PCI patients with particular emphasis on periprocedural stent thrombosis. A total of 18 randomised clinical trials involving 41,752 subjects were included. The endpoints comprised: net adverse clinical event (NACE: death, myocardial infarction [MI], unscheduled revascularisation, major bleeding), major adverse cardiovascular event (MACE: death, MI, or stroke), and acute/subacute stent thrombosis (ST). A subanalysis for planned and provisional glycoprotein IIb/IIIa inhibitor (GPI) use with heparin was performed. Results were presented as risk ratios (RR) and 95% confidence intervals (CI). Bivalirudin significantly reduced NACE risk (RR 0.85, 95% CI 0.76-0.96) and increased the incidence of MI (RR 1.09, 95% CI 1.01-1.18), ST (RR 1.50, 95% CI 1.13-1.99), and MACEs (RR 1.06, 95% CI 0.99-1.13). Comparing to heparin with provisional or planned GPI use, there was higher risk of acute ST with bivalirudin (RR 2.14, 95% CI 1.01-4.56 and RR 5.53, 95% CI 2.32-13.18, respectively). Comparing to heparin and provisional GPIs, bivalirudin failed to reduce NACEs and major bleeding. However, it decreased rates of NACEs (RR 0.81, 95% CI 0.69-0.96) and major bleeding (RR 0.64, 95% CI 0.48-0.85) compared with heparin and planned GPI use. The advantages of bivalirudin are undoubtedly related to GPI use in the heparin arms. Bivalirudin-based regimens are more beneficial when compared with heparin and planned GPI use in terms of NACE and major bleedings; this was not observed when compared to heparin and provisional GPI use. Regardless of adjunctive GPI use, stent thrombosis episodes were significantly more common in bivalirudin-treated subjects. Therefore, the safety and economic issues may urge revision of this aspect of current clinical practice and guidelines.

Comparison of heparin, bivalirudin, and different glycoprotein IIb/IIIa inhibitor regimens for anticoagulation during percutaneous coronary intervention: A network meta-analysis.

Numerous GPIs are available for PCI. Although they were tested in randomized controlled trials, a comparison between the different GPI strategies is lacking. Thus, we performed a Bayesian network meta-analysis to compare different glycoprotein IIb/IIIa inhibitor (GPI) strategies with heparin and bivalirudin for percutaneous coronary intervention (PCI). MEDLINE, Cochrane CENTRAL, and ClinicalTrials.gov were searched by two independent reviewers for randomized controlled trials comparing high-dose bolus tirofiban, abciximab, eptifibatide, heparin with provisional glycoprotein IIb/IIIa inhibitors, and bivalirudin with provisional GPI that reported clinical outcomes. Mixed treatment comparison model generation was performed to directly and indirectly compare between different anticoagulation strategies for all-cause mortality, myocardial infarction, major adverse cardiovascular events, major bleeding, minor bleeding, need for transfusion, and thrombocytopenia. A total of 41 randomized controlled trials with 38,645 patients were included in the analysis, among which 2654 were randomized to high-dose bolus tirofiban, 6752 to abciximab, 1669 to eptifibatide, 16,500 to heparin, and 11,070 to bivalirudin. Mean age was 64±11years, 75% were male, 91% were treated with stenting, 71% with clopidogrel, and 74% for acute coronary syndrome. High-dose bolus tirofiban was associated with a significant reduction in all-cause mortality compared with heparin (OR 0.57 [credible intervals 0.37, 0.9]) and eptifibatide (OR 0.44 [credible intervals 0.19, 1.0]). GPI regimens had less myocardial infarction and major adverse cardiovascular events but greater bleeding compared with heparin and bivalirudin. There was no difference among the GPI therapies for other outcomes, including myocardial infarction, major adverse cardiovascular events, and major bleeding. Our network meta-analysis of 38,645 patients demonstrated that GPI regimens were associated with a reduction in recurrent myocardial infarction or major adverse cardiovascular events for PCI, while bivalirudin was associated with the lowest risk of bleeding.

Heparin: Physiology, Pharmacology, and Clinical Application.

Heparin is stored endogenously within the secretory granules of basophils and mast cells, and is only released into the vasculature at sites of injury. At these sites, it helps maintain proper blood flow by balancing the active anticoagulant and procoagulant processes. Pharmaceutical-grade heparin is derived from animal tissue, but one form is made synthetically. Heparin is commonly used in the management of coronary artery disease, deep vein thrombosis, pulmonary embolism, and atrial fibrillation, and in the prevention of thrombosis during cardiopulmonary bypass and extracorporeal membrane oxygenation. Heparin treatment is a key component in elective percutaneous coronary intervention (PCI). It plays an important role in minimizing the risk of thrombotic events during PCI and is one of the most popular anticoagulants used. However, some studies show that higher heparin doses are associated with more frequent bleeding complications, which can increase morbidity and mortality. The optimal heparin dosing regimens are still debated, as well as their efficacy in PCI compared with that of other drugs such as bivalirudin. This review examines the physiology, pharmacology, therapeutic applications, dosing regimens, and efficacy of heparin in the setting of PCI. In addition, included is a review of data on addition of glycoprotein IIb/IIIa inhibitors to heparin and comparison of heparin monotherapy to bivalirudin in PCI.

Bivalirudin in percutaneous coronary intervention, is it the anticoagulant of choice?

For decades, unfractionated heparin (UFH) has been widely used in catheterization laboratories for anticoagulation for percutaneous coronary intervention (PCI). The direct thrombin inhibitors, bivalirudin, has emerged as an alternative to UFH for PCI procedures, due to its lower bleeding risk. More recently, randomized trials and meta-analyses questioned the efficacy of bivalirudin, and demonstrated that bivalirudin might be associated with a higher incidence of ischemic events and in particular stent thrombosis. In this review, we discuss the pharmacology of bivalirudin along with the clinical evidence comparing bivalirudin versus UFH in patients undergoing PCI for various indications.

Enhancing the Benefit of Bivalirudin in Percutaneous Coronary Intervention: Is High Risk of Bleeding the Key?

Bivalirudin is a potent direct thrombin inhibitor that can reduce thrombus burden during acute coronary syndromes (ACS) and percutaneous coronary intervention (PCI) by blocking formation of fibrin and by suppressing platelet aggregation [1]. When compared with heparin, bivalirudin has several theoretical mechanistic advantages that include activity against clot-bound thrombin, inhibition of thrombin-induced platelet activation, short plasma half-life, linear pharmacokinetics less affected by plasma proteins and renal insufficiency, and an unaffected platelet activation during PCI [1]. These properties of bivalirudin provide a more predictable inhibition of coagulant activity than does heparin, with less degree of inter-patient variability in anticoagulation response. Moreover, its binding to thrombin is non-competitive and reversible, and hemostatic capacity is more readily restored; hence bleeding, as well as ischemic complications, may be reduced [2]. In the first randomized trial (HAS [Hirulog Angioplasty Study]) comparing bivalirudin with heparin in over 4000 patients undergoing PCI for unstable or post-infarction angina, bivalirudin was at least as effective as high-dose heparin in preventing ischemic complications, and it carried a lower risk of bleeding [3]. Nevertheless, development of bivalirudin was suspended because of the unfavorable cost comparison with heparin. Only recently did the development of a less expensive manufacturing process encourage interest from researchers to further support the efficacy and safety of this anticoagulant therapy. Re-analysis of the original HAS using contemporary endpoints and intention-to-treat analysis showed a 22 % reduction in major adverse cardiac events (including death, ACS, and revascularization) and a 62 % reduction in bleeding with bivalirudin at 7 days [4]. In the REPLACE-2 (Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events) trial [5], bivalirudin with provisional glycoprotein IIb/IIIa blockade (which was administered in about 7 % of patients) was proven to be statistically non-inferior to heparin plus planned glycoprotein IIb/IIIa inhibitors during PCI with regard to suppressing ischemic events after PCI, but was superior in preventing hemorrhagic complications. More recently, bivalirudin provided similar protection from ischemic events as glycoprotein IIb/IIIa inhibitors, but with lower bleeding rates in the ACUITY (Acute Catheterisation and Urgent Intervention Triage strategy) trial [6]. Although the evidentiary landscape in support of antithrombotic treatment choices during PCI has been enriched by these trials, recent data from clinical trials and pooled analyses questioned the role of bivalirudin in the setting of planned and primary PCI [7–12]. In the HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trial, the use of bivalirudin was associated with a This comment refers to the article available at doi:110.1007/s40256015-0113-8.

Heparin is Not Inferior to Bivalirudin in Percutaneous Coronary Intervention-Focusing on the Effect of Glycoprotein IIb/IIIa Inhibitor Use: A Meta-Analysis.

Our aim was to compare the efficacy and safety of bivalirudin (Biv) versus heparin (Hep) with or without similar usage rate of glycoprotein IIb/IIIa inhibitors (GPIs) during percutaneous coronary intervention (PCI). The PubMed and EMbase were searched. Randomized trials comparing Biv versus Hep were eligible for inclusion. With imbalanced GPI use, Biv had significantly lower major bleeding (pooled risk ratio [RR], 0.67; 95% confidence interval [CI], 0.54-0.83) without difference in mortality (pooled RR, 0.95; 95% CI, 0.80-1.14). With comparable GPI use, no significant difference was observed in major bleeding (pooled RR, 0.95; 95% CI, 0.82-1.10) and mortality (pooled RR, 1.13; 95% CI, 0.85-1.50). With no GPI use, Biv was associated with numerically higher mortality (pooled RR, 1.17; 95% CI, 0.83-1.65) without significant difference in major bleeding (pooled RR, 0.81; 95% CI, 0.64-1.02). In conclusion, when comparing different anticoagulants during PCI, the effect of GPIs should not be underestimated. Heparin as such was found noninferior to Biv.

Meta-Analysis of Randomized Clinical Trials Comparing Bivalirudin Versus Heparin Plus Glycoprotein IIb/IIIa Inhibitors in Patients Undergoing Percutaneous Coronary Intervention and in Patients With ST-Segment Elevation Myocardial Infarction

This study sought to investigate the relative safety and efficacy of bivalirudin versus heparin plus glycoprotein (GP) IIb/IIIa inhibitors in patients undergoing percutaneous coronary intervention (PCI) and in those with ST-segment elevation myocardial infarction (STEMI). The safety of bivalirudin in PCI, particularly in patients with STEMI, continues to be debated. We searched the on-line databases for randomized controlled trials of bivalirudin versus heparin plus GP IIb/IIIa inhibitors. Data on study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes at 30 days were extracted. A total of 19,856 PCI patients included in 7 randomized trials and 5,820 patients with STEMI included in 2 randomized trials were separately analyzed. At 30 days, bivalirudin use in patients undergoing PCI resulted in similar rates of death, myocardial infarction, repeat revascularization, and stent thrombosis. In patients with STEMI, bivalirudin use resulted in decreased cardiac mortality (risk ratio [RR] 0.70, 95% confidence interval [CI] 0.50 to 0.97, p=0.03) compared with heparin plus GP IIb/IIIa inhibitors but an increase in definite stent thrombosis at 30 days (RR 1.88, 95% CI 1.09 to 3.24, p=0.02) driven by an increase in acute stent thrombosis (RR 5.48, 95% CI 2.30 to 13.07, p=0.0001). Bivalirudin use was associated with a decrease in Thrombolysis In Myocardial Infarction (TIMI) major (RR 0.58, 95% CI 0.46 to 0.74, p<0.0001) and TIMI minor (RR 0.55, 95% CI 0.48 to 0.63, p<0.0001) bleeding rates in PCI patients as well as in a subgroup of patients with STEMI. In conclusion, in PCI patients anticoagulation with bivalirudin results in similar ischemic adverse events and a reduction in TIMI major and minor bleeding at 30 days compared with heparin plus GP IIb/IIIa inhibitors. In patients with STEMI, bivalirudin use is associated with a reduction in TIMI major and minor bleeding and fewer deaths from cardiac causes but an increase in acute and 30-day definite stent thrombosis.

Collagen Plug Vascular Closure Devices and Reduced Risk of Bleeding with Bivalirudin Versus Heparin Plus Abciximab in Patients Undergoing Percutaneous Coronary Intervention for Non ST‐Segment Elevation Myocardial Infarction

In ISAR-REACT-4 (abciximab and heparin vs. bivalirudin for non-ST-elevation myocardial infarction [NSTEMI]), bivalirudin reduced the risk of bleeding after percutaneous coronary intervention (PCI) compared with unfractionated heparin plus abciximab (UFH + abciximab). Vascular closure devices (VCDs) may also prevent bleeding complications, and thus attenuate the benefit of bivalirudin. This analysis examined whether there exists an interaction on bleeding between VCDs and bivalirudin versus UFH + abciximab after PCI. Patients with NSTEMI were randomly assigned to either receive UFH + abciximab or bivalirudin for PCI. The use of a VCD after femoral access was left to the operator's discretion. The effect of randomized treatment in patients who received a VCD was compared to that in patients with manual compression of the femoral access site. The primary end-point of this analysis was the 30-day incidence of ISAR-REACT-4 major bleeding. A total of 1,711 patients were enrolled in this analysis. Among the 365 (21.3%) patients receiving a VCD, 188 (51.5%) were treated with UFH + abciximab and 177 (48.5%) with bivalirudin. ISAR- REACT-4 major bleeding was higher with UFH + abciximab than with bivalirudin, independent of whether a VCD was used (4.8% vs. 2.3% with VCD and 4.6% vs. 2.7% without VCD, Pint = 0.76). There were also no interactions between randomized treatment and VCDs with respect to any of the ischemic end-points or net clinical outcome (Pint > 0.56). In patients undergoing PCI for NSTEMI, the reduction of major bleeding by bivalirudin compared with UFH + abciximab was not affected whether a VCD was used.

Comparison of Bivalirudin and Radial Access Across a Spectrum of Preprocedural Risk of Bleeding in Percutaneous Coronary Intervention

Background— Bleeding is a common, noncardiac, preventable complication of percutaneous coronary intervention. We compared the relative safety of radial access and bivalirudin in percutaneous coronary intervention. Methods and Results— From CathPCI Registry, we determined the association between the site of arterial access, bivalirudin, and periprocedural bleeding rates in 501 017 patients. Radial access patients receiving heparin (radial group) were compared with those receiving bivalirudin (radial combination group). Femoral access patients who had bivalirudin and a vascular closure device served as a reference group (femoral group). An inverse probability weighting analysis incorporating propensity scores was used to compare groups. The overall rate of bleeding was 2.59%. It was 2.71% in the femoral group, 2.5% in the radial group, and 1.82% in the radial combination groups ( P &lt;0.001). When compared with femoral group, the adjusted odds ratio for bleeding was significantly lower for patients with radial combination group (odds ratio, 0.79; 95% confidence interval, 0.72–0.86), but not for radial group (odds ratio, 0.96; 95% confidence interval, 0.88–1.05), unless patients treated with IIb/IIIa were excluded (radial group-IIb/IIIa odds ratio, 0.84; 95% confidence interval, 0.75–0.94).The number needed to treat to prevent 1 bleeding event with radial combination group was 138, whereas the number needed to treat to prevent 1 bleeding event in high-bleeding risk patients was 68. Conclusions— In this observational analysis, the combination of bivalirudin and radial access was associated with reduced bleeding event rate. This benefit was present across the entire spectrum of preprocedural risk of bleeding, with or without exposure to IIb/IIIa inhibitors. These data support an adequately powered randomized trial comparing bleeding avoidance strategies.

Safety of bivalirudin in percutaneous coronary intervention following thrombolytic therapy

This study was undertaken to evaluate the safety of bivalirudin (BIV) use during percutaneous coronary intervention (PCI), following thrombolytic therapy in patients with ST-segment elevation myocardial infarction (STEMI). BIV has emerged as a safer anticoagulant than unfractionated heparin (UFH) during primary PCI; however, its use in patients who receive thrombolytic therapy has not been established. A consecutive series of 104 patients who presented with STEMI treated with full-dose thrombolytics and who subsequently received PCI within 6 hr was identified and analyzed. BIV use was compared with UFH for in-hospital bleeding and ischemic events. The primary end points were the rate of major bleeding and the rate of net adverse clinical events as defined in the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction trial. The study cohort consisted of 104 patients, of whom 47 (45%) received BIV and 57 (55%) received UFH. Patients on BIV were more frequently preloaded with clopidogrel, while intraprocedural glycoprotein IIb/IIIa inhibitors were used only in UFH patients. In-hospital death, ischemic events, and thrombolysis in myocardial infarction major bleeding occurred more frequently in patients treated with UFH. The net adverse clinical events rate was lower in the intraprocedural BIV group (3 [6.4%] vs. 12 [21.1%] UFH, P = 0.034). The use of BIV in patients presenting with STEMI who were pretreated with thrombolytic therapy and who subsequently underwent PCI is safe and is associated with less ischemic and bleeding events when compared with UFH, and should be considered as the first line anticoagulant for these patients during PCI.

The Role of Bivalirudin in Percutaneous Coronary Intervention

plus GP IIb/IIIa inhibitor (7.7% and 7.3%, respectively). There were also similar rates of major bleeding (5.3% and 5.7%). As compared with heparin plus GP IIb/IIIa inhibitor, bivalirudin, alone, led to noninferior rates of ischemia (7.8% and 7.3%, respectively; P=0.32), and significantly reduced major bleeding (3.0% vs. 5.7%; P<0.001). [7] Bivalirudin also underwent evaluation in the setting of STEMI patients. In the Bivalirudin during Primary PCI in Acute Myocardial Infarction(HORIZONS-AMI trial) [8]. This was a multicenter trial that enrolled 3602 patients with ST-segment elevation myocardial infarction who were undergoing primary PCI. The patients were randomized to a regimen of heparin plus a GP IIb/IIIa inhibitor versus bivalirudin alone. Treatment with bivalirudin alone, as compared with heparin plus GP IIb/IIIa inhibitors was associated with a significant reduction in the 30-day primary endpoint of net adverse clinical events which was predominantly driven by a lower rate of major bleeding. It also lowered 30-day rates of death from cardiac causes (1.8% vs. 2.9% P=0.03) as well as death from all causes (2.1% vs. 3.1% P=0.047). Follow up at one, two, and three years showed that the reduction in the incidence of net adverse clinical events and major bleeding was robustly maintained in the bivalirudin monotherapy group. [8] Conclusion Bivalirudin represents an attractive option as an antithrombotic agent in the cardiac catheterization laboratory. It has several advantages over heparin, and based upon evidence from many clinical trials, it has been proven to be safer than and at least as effective as heparin in the STEMI, NSTEMI/UA, and elective PCI population. We expect that the use of this agent as an antithrombotic therapy during PCI will continue to gain traction in the next few years.

Clinical expert consensus statement on best practices in the cardiac catheterization laboratory: Society for cardiovascular angiography and interventions

The cardiac catheterization laboratory (CCL) is a setting in which elective, urgent, and emergent percutaneous procedures are performed. This poses challenges to maintaining and prioritizing high quality care and patient safety. Nonetheless, process expectations of a high-quality CCL include appropriate periprocedural communication, clinical management, documentation, and universal protocol. Regulations primarily targeted at open surgical operating rooms have the potential to negatively impact care because they may mandate focus on performance measures that are not necessarily relevant to the cardiac catheterization laboratory. For example, routine site marking for percutaneous access is irrelevant for most patients since failure to obtain access on one side (e.g., right femoral artery) simply leads to attempting access on the other side (e.g., left femoral artery). Instead, directives should be tailored to the percutaneous procedure setting to assure quality and optimal patient safety. This document will therefore provide expert consensus opinion on a number of issues pertaining to ‘‘best practices’’ within the CCL, focusing on quality and safety during each step of the process. The writing committee acknowledges a dearth in high-quality published studies in this area, making many of the enclosed recommendations based primarily on expert consensus. Although references are provided when available, further research specifically in catheterization laboratory processes and quality improvement is needed. The document is divided into ‘‘best practices’’ that should be performed during the preprocedure, intraprocedure, and postprocedure settings for diagnostic cardiac catheterization and coronary intervention, to be consistent with the typical patient flow into and out of the CCL. Despite the long history of cardiac catheterization that dates back several decades, a document describing these ‘‘best practices’’ has not yet been written. The purpose of this document is not to represent all acceptable practices, but to provide consensus opinion on what would currently be considered ‘‘best practices’’ as future goals for catheterization laboratories.

Safety and efficacy of bivalirudin for percutaneous coronary intervention with rotational atherectomy

Safety and efficacy of bivalirudin for percutaneous coronary intervention with rotational atherectomy

Safety and Efficacy of Bivalirudin for Percutaneous Coronary Intervention with Rotational Atherectomy

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.

Eptifibatide-Associated Acute, Profound Thrombocytopenia

To describe 3 cases of eptifibatide-associated acute, profound thrombocytopenia. A 40-year-old black female received eptifibatide 180-microg/kg double bolus followed by a continuous infusion of 2 microg/kg/min for percutaneous coronary intervention (PCI). The platelet count decreased from 308 x 10(3)/mm3 to 2 x10(3)/mm3 4 hours after initiation of eptifibatide. Eptifibatide was discontinued and platelets were transfused. The patient developed a hematoma and petechiae. A 67-year-old white female received the same dosage regimen of eptifibatide for PCI with no serious adverse effects, with the treatment repeated one month later. At that time, she developed chest and back pain, dyspnea, wheezing, and hypotension after the first bolus. Her platelet count decreased from 334 x10(3)/mm3 to 6 x10(3)/mm3 24 hours after initiation. Eptifibatide was discontinued and platelets were transfused. The patient died due to shock. A 72-year-old white male received eptifibatide 180-microg/kg double bolus followed by a continuous infusion of 2 microg/kg/min for acute coronary syndrome. His platelet count decreased from 189 x10(3)/mm3 to 17 x10(3)/mm3, and eptifibatide was discontinued. Eptifibatide was readministered with bivalirudin for PCI once the platelet count increased to 94 x10(3)/mm3. Sixteen hours later, the platelet count decreased to 1 x 10(3)/mm3. Eptifibatide was discontinued and platelets were transfused. The patient developed a hematoma. Acute, profound thrombocytopenia is a rare complication of glycoprotein IIb/IIIa inhibitor therapy characterized by a precipitous decline in platelet count to <20 x10(3)/mm3 within 24 hours of therapy. An objective causality assessment revealed that the adverse drug event was probable in 2 cases and possible in the other. Increasing use of the glycoprotein IIb/IIIa inhibitors and enhanced recognition of the potential for acute, profound thrombocytopenia reinforce the need for more vigilant monitoring and alternative management strategies.

Safe and efficacious use of bivalirudin for percutaneous coronary intervention with adjunctive platelet glycoprotein IIb/IIIa receptor inhibition

22 (13%) 16 (10%) 0.32 Prior MI 57 (33%) 53 (33%) 0.97 Prior coronary angioplasty 76 (44%) 62 (38%) 0.08 Prior coronary bypass 62 (36%) 66 (41%) 0.21 Smoker 34 (20%) 24 (15%) 0.38 Chronic renal insufficiency 6 (3.4%) 6 (3.7%) 0.92 ACE inhibitor 38 (22%) 42 (26%) 0.28 blockers 57 (33%) 39 (24%) 0.07 Thienopyridines 60 (35%) 66 (41%) 0.33 Statins 69 (40%) 65 (40%) 0.92 GP IIb/IIIa inhibitor use 155 (90%) 133 (82%) 0.02 Ejection fraction 50% 12% 50% 11% 0.12 ACC/AHA score B2/C 84 (49%) 96 (59%) 0.19 Closure device 115 (67%) 104 (64%) 0.12 Multivessel intervention 29 (17%) 24 (15%) 0.45 Stents 138 (80%) 125 (77%) 0.41

Evolving role of bivalirudin in percutaneous coronary interventions; impact of the REPLACE-2 study

Percutaneous coronary interventions are being used with increasing frequency nowadays for the treatment of patients with coronary heart disease. Acute thrombotic complications remain one of the major limitations of these procedures for which unfractionated heparin has been the standard foundation anticoagulant. It has, however, many limitations and disadvantages that necessitated research and development of alternative anticoagulant therapies. The direct thrombin inhibitor bivalirudin has been approved as a substitute for heparin in patients undergoing angioplasty for unstable angina based on data in higher-risk patients where bivalirudin resulted in lower rates of ischaemic and bleeding complications compared to heparin. This evidence was collected prior to the widespread use of platelet glycoprotein (GP) IIb/IIIa receptor blockers, thienopyridines and intracoronary stents, considered standard practice for such patients today. The REPLACE-2 study was carried out to establish whether, in the current era, bivalirudin used with provisional GP IIb/IIIa blockade if necessary during the procedure could provide equivalent protection from ischaemic events compared with the gold standard of heparin plus routine GP IIb/IIIa blockade. With advantages with regards to bleeding, ease of use and reduced cost, bivalirudin use with provisional GP IIb/IIIa inhibitors in low-to-moderate risk percutaneous coronary interventions allows GP IIb/IIIa receptor antagonists to be used in a selective fashion, rather than in all patients. In this article, background rationale for bivalirudin use in this setting is reviewed as well as past research in this area. Additionally, the implications of the REPLACE-2 study in establishing where bivalirudin fits into our current interventional cardiology practice and future directions are presented.