Impact of home warfarin use on the treatment and outcomes of patients undergoing percutaneous coronary intervention

The periprocedural management, bleeding risks, and outcomes of patients taking warfarin previous to percutaneous coronary intervention (PCI) have not been well characterized. All patients undergoing PCI in the National Cardiovascular Data Registry from January 1, 2004 to March 31, 2006 were analyzed (n = 307,443). Multivariable modeling was used to evaluate the association between home warfarin use and in-hospital mortality and bleeding (requiring blood transfusion and/or prolonging hospital stay and/or causing hemoglobin drop >3.0 g/dl). Patients undergoing elective PCI and urgent PCI (primary/rescue/facilitated PCI with symptoms fewer than 24 hours) were analyzed separately. Overall, 11,173 patients (3.6%) were taking warfarin previous to PCI. Compared with patients not taking warfarin, patients taking warfarin were older and had greater burden of comorbidities. Patients taking warfarin were less likely to receive aspirin, theinopyridines, and glycoprotein IIb-IIIa antagonists during PCI. Unadjusted bleeding rates (elective PCI = 3.2% vs 1.9%; urgent PCI = 8.2% vs 4.8%) and in-hospital mortality (elective PCI = 1.4% vs. 0.6%; urgent PCI = 8.6% vs. 4.5%) were higher among patients taking warfarin. After adjustment for clinical characteristics, the risk of in-hospital mortality was similar with and without previous warfarin use. However, the adjusted risk of bleeding was significantly higher in patients receiving warfarin, for both elective (odds ratio = 1.26, 95% confidence interval = 1.09 to 1.46) and urgent PCI (odds ratio = 1.42, 95% confidence interval = 1.14 to 1.76). In conclusion, while fewer than 5% of patients undergoing PCI are taking previous warfarin, these patients have a higher risk of in-hospital bleeding events but a similar risk of mortality despite lower use of antiplatelet agents.     

Percutaneous coronary intervention in patients receiving enoxaparin or unfractionated heparin after fibrinolytic therapy for ST-segment elevation myocardial infarction in the ExTRACT-TIMI 25 trial.

OBJECTIVES: We sought to evaluate whether enoxaparin (ENOX) is superior to unfractionated heparin (UFH) as adjunctive therapy for patients with ST-segment elevation myocardial infarction (STEMI) who receive fibrinolytic therapy and subsequently undergo percutaneous coronary intervention (PCI) by analyzing data from the ExTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction 25) trial. BACKGROUND: Limited data are available on the use of ENOX compared with UFH as adjunctive therapy in STEMI patients treated with fibrinolytic therapy and subsequent PCI. METHODS: A total of 20,479 STEMI patients who received fibrinolytic therapy were randomized to a strategy of ENOX throughout index hospitalization or UFH for at least 48 h, with blinded study drug to continue if PCI was performed. The primary end point of death or recurrent MI through 30 days was compared for ENOX versus UFH among the patients who underwent subsequent PCI (n = 4,676). RESULTS: After initial fibrinolysis, fewer patients underwent PCI through 30 days in the ENOX versus the UFH group (22.8% vs. 24.2%; p = 0.027). Among patients who underwent PCI by 30 days, the primary end point occurred in 10.7% of ENOX and 13.8% of UFH patients (0.77 relative risk; p < 0.001). There were no differences in major bleeding for ENOX versus UFH (1.4% vs. 1.6%; p = NS). Results were similar when PCI was carried out in patients receiving blinded study drug during PCI (n = 2,178). CONCLUSION: Among patients treated with fibrinolytic therapy for STEMI who underwent subsequent PCI, ENOX administration was associated with a reduced risk of death or recurrent MI without difference in the risk of major bleeding. The strategy of ENOX support for fibrinolytic therapy followed by PCI is superior to UFH and provides a seamless transition from the medical management to the interventional management phase of STEMI without the need for introducing a second anticoagulant in the cardiac catheterization laboratory.     

Efficacy and safety of triple antiplatelet therapy with and without concomitant anticoagulation during elective percutaneous coronary intervention (the REMOVE trial)

Adjunctive glycoprotein IIb/IIIa inhibition decreases ischemic events after percutaneous coronary intervention (PCI) but is associated with increased bleeding. We hypothesized that maximal antiplatelet therapy with aspirin, a thienopyridine, and a glycoprotein IIb/IIIa inhibitor without unfractionated heparin (UFH) would result in fewer bleeding complications and maintain efficacy in elective PCI. A total of 159 patients undergoing elective PCI were randomized to intraprocedural eptifibatide alone or eptifibatide plus UFH. Patients received aspirin 325 mg and clopidogrel 300 mg before the procedure. The primary end point was the Landefeld bleeding index. Secondary end points included the composite clinical outcome of in-hospital death, myocardial infarction, urgent target vessel revascularization, and Thrombolysis In Myocardial Infarction major bleeding, and a composite bleeding outcome of major, minor, and nuisance bleeding. The Landefeld bleeding index was significantly lower in the eptifibatide-only group compared with the eptifibatide-plus-UFH group (3.0 vs 3.9, p = 0.03). There was no significant difference in the composite clinical end point between groups (eptifibatide only 17% vs eptifibatide plus UFH 15%, p = 0.7). There was a trend toward a decrease in the composite bleeding end point in the eptifibatide-only compared with the eptifibatide-plus-UFH group (43% vs 56%, p = 0.10). In conclusion, during elective PCI, a strategy of aggressive antiplatelet therapy using aspirin, clopidogrel, and eptifibatide without anticoagulant therapy appears to decrease bleeding complications.     

Bivalirudin in PCI: an overview of the REPLACE-2 trial

The Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial is one of the largest acute randomized controlled trials evaluating the efficacy of two anticoagulant strategies during contemporary urgent or elective percutaneous coronary intervention (PCI). The direct thrombin inhibitor, bivalirudin, with provisional use of glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitor was compared to low-dose unfractionated heparin (UFH) plus planned GP IIb/IIIa inhibitor. At 30-day follow-up, the primary quadruple composite endpoint (death, myocardial infarction (MI), urgent repeat revascularization, or in-hospital major bleeding) occurred in 9.2% of patients in the bivalirudin group versus 10.0% of patients in the UFH plus GP IIb/IIIa inhibitor group. The secondary triple composite endpoint (death, MI, urgent repeat revascularization) occurred in 7.6% of patients in the bivalirudin group compared with 7.1% of patients in the UFH plus GP IIb/IIIa inhibitor group. Both endpoints met formal statistical criteria for noninferiority to UFH plus GP IIb/IIIa inhibitor. By imputed comparison from historic GP IIb/IIIa trials between bivalirudin versus UFH alone, REPLACE-2 demonstrated that bivalirudin was superior to UFH alone with respect to the quadruple and triple composite endpoints. Furthermore, bivalirudin plus provisional GP IIb/IIIa blockade was associated with a significant reduction in in-hospital bleeding (2.4% vs. 4.1%; p < 0.001). At 6 months' follow-up, there was no significant difference in rates of death, MI, or revascularization between the two groups. Furthermore, there was no evidence that the early, nonsignificant 0.5% excess non-Q-wave MI in the bivalirudin group translated into later mortality. There was a trend toward decreased mortality at 6 months in the bivalirudin arm (0.95% vs. 1.35%; p = 0.148). The relative efficacy of bivalirudin versus UFH plus GP IIb/IIIa inhibitor was similar in several high-risk subgroups, including patients with diabetes mellitus or prior MI, women, the elderly (age > 65 years), and patients undergoing PCI of bypass grafts. Bivalirudin represents an exciting alternative to UFH plus GP IIb/IIIa inhibitor in patients undergoing urgent and elective PCI with similar suppression of ischemic events, fewer bleeding complications, and the potential for greater cost savings and ease of administration.     

Efficacy and safety of enoxaparin versus unfractionated heparin in patients with ST-segment elevation myocardial infarction also treated with clopidogrel.

OBJECTIVES: The purpose of this study was to determine the efficacy and safety of enoxaparin (ENOX) versus unfractionated heparin (UFH) in patients with ST-segment elevation myocardial infarction (STEMI) receiving fibrinolytic therapy with and without clopidogrel. BACKGROUND: The efficacy and safety of ENOX and clopidogrel given together in STEMI remains to be defined. METHODS: We compared the rates of major adverse cardiovascular events (MACE) as well as the rates of bleeding in medically managed patients randomized to ENOX versus UFH in the ExTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction 25) trial, stratified by concomitant clopidogrel use. RESULTS: Enoxaparin significantly reduced the rate of the composite of death, recurrent myocardial infarction, myocardial ischemia, or stroke, compared with UFH, both in patients (n = 2,173) treated with clopidogrel (10.8% vs. 13.9%, adjusted odds ratio [OR(adj)] 0.70, p = 0.013) and in patients (n = 12,918) not treated with clopidogrel (13.3% vs. 15.3%, OR(adj) 0.85, p = 0.003) with no evidence of heterogeneity (p(interaction) = 0.21). The excess risk of TIMI major bleeding with ENOX versus UFH was numerically but not statistically significantly higher in patients treated with clopidogrel (2.7% vs. 1.0%) versus those who were not (2.1% vs. 1.2%) (p(interaction) = 0.61). Net clinical benefit (MACE and major bleeding) favored treatment with ENOX over UFH, either with concomitant clopidogrel (absolute risk reduction 2.4%, 95% confidence interval [CI] -0.5% to 5.3%) or without (absolute risk reduction 1.7%, 95% CI 0.5% to 3.0%) (p(interaction) = 0.61). CONCLUSIONS: In patients with STEMI receiving fibrinolytic therapy, the net benefit of ENOX is similar in patients who are and are not treated with clopidogrel. The totality of trial data suggest that the combination of a fibrinolytic, aspirin, clopidogrel, and ENOX offers an attractive pharmacologic reperfusion strategy in STEMI.     

Enoxaparin vs. unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction in elderly and younger patients: results from ExTRACT-TIMI 25.

AIMS: To determine the effects of age on outcomes in patients with STEMI treated with a strategy of enoxaparin (ENOX) vs. unfractionated heparin (UFH). METHODS AND RESULTS: In the ExTRACT-TIMI 25 trial, 20,479 patients with STEMI were randomized in a double-blind fashion to UFH or ENOX. A novel reduced dose of ENOX was administered to patients >or=75 years, and a reduced dose in those with an estimated creatinine clearance of < 30 mL/min. Anti-Xa levels were measured in a subset of patients (n = 73). The exposure to anti-Xa over time was lower in the elderly (AUC(0-12 h) P < 0.0001; AUC(steady-state) P = 0.0046). The relative risk reduction (RR) with ENOX on the primary endpoint, i.e. death or non-fatal recurrent myocardial infarction, was greater in patients < 75 years (20%) than > 75 years (6%), but the absolute benefits were similar. When compared with UFH, ENOX was associated with an RR of 1.67 for major bleeding, but the magnitude of the excess risk tended to be lower (RR = 1.15) in patients >or= 75 years assigned to ENOX. CONCLUSION: A dose reduction of ENOX in the elderly appears to be helpful in ameliorating bleeding risk. A strategy of ENOX was superior to UFH in both young and elderly patients with STEMI treated with fibrinolysis.     

Bleeding risk and outcomes of Bivalirudin versus Glycoprotein IIb/IIIa inhibitors with targeted low-dose unfractionated Heparin in patients having percutaneous coronary intervention for either stable or unstable angina pectoris

For patients undergoing elective percutaneous coronary intervention (PCI), procedural anticoagulation with bivalirudin was previously shown to significantly reduce bleeding complications at the cost of a modest increase in ischemic events compared with unfractionated heparin (UFH) and glycoprotein IIb/IIIa inhibitors (GPIs). However, the excess bleeding in patients treated with UFH and GPIs may have been caused by excessively high UFH doses and increased activated clotting times. This study sought to determine the bleeding risk of targeted low-dose UFH with GPIs compared with bivalirudin in patients undergoing elective PCI. Of 1,205 patients undergoing elective PCI, 602 underwent PCI with adjunctive UFH and GPIs with the UFH dose targeted to an activated clotting time of approximately 250 seconds, and 603 patients matched for baseline characteristics underwent PCI with bivalirudin. Outcomes were analyzed for major bleeding (hematocrit decrease >15%, gastrointestinal bleed, or major hematoma) and 6-month major adverse cardiac events (death, myocardial infarction, and target-lesion revascularization). The maximum activated clotting time achieved was 261.7 +/- 61.6 seconds in the UFH/GPI group and 355.4 +/- 66.6 in the bivalirudin group (p <0.001). In-hospital major bleeding rates were similar between groups (1.8% UFH/GPI vs 1.7% bivalirudin; p = 0.83), as were transfusion requirements (1.2% UFH/GPI vs 0.5% bivalirudin; p = 0.61). The 6-month major adverse cardiac event rate was also similar between groups (9.5% UFH/GPI vs 9.0% bivalirudin; p = 0.81). In conclusion, there were no significant differences in major bleeding and 6-month major adverse cardiac events for patients undergoing elective PCI treated with targeted low-dose UFH and GPIs compared with those treated with bivalirudin.     

A novel point-of-care enoxaparin monitor for use during percutaneous coronary intervention. Results of the Evaluating Enoxaparin Clotting Times (ELECT) Study

OBJECTIVES: The aim of this study was to discern a target range of anticoagulation for enoxaparin during percutaneous coronary intervention (PCI) as measured by the Rapidpoint ENOX (Pharmanetics Inc., Morrisville, North Carolina), a new point-of-care test. BACKGROUND: In the U.S., enoxaparin has been used in only a small proportion of PCI procedures, partly because a rapid enoxaparin-specific assay was unavailable. METHODS: We analyzed data from 445 enrolled patients receiving subcutaneous or intravenous enoxaparin in a prospective, multicenter study. Serial anticoagulation measurements and clinical outcomes were recorded. RESULTS: The in-hospital composite occurrence of death, myocardial infarction, and urgent target vessel revascularization was 5.4%, and Thrombolysis In Myocardial Infarction (TIMI) major bleeding, minor bleeding, and any reported bleeding occurred in 0.2%, 1.3%, and 7.9% of patients, respectively. No significant association between procedural ENOX times and ischemic events was observed (p = 0.222), although the event rate was 4.0% among those with ENOX times between 250 to 450 s versus 7.2% for those outside this range (p = 0.134). Increasing ENOX time at sheath removal was correlated with any bleeding (p = 0.010) with a 1% increase for every approximately 30-s rise. CONCLUSIONS: Ischemic events were infrequent, and the rate appeared lowest in the mid-range of ENOX times. Bleeding events increased with increasing ENOX times. These observations, combined with a suggested procedural anti-Xa level of 0.8 to 1.8 IU/ml, translate into a recommended ENOX time range of 250 to 450 s for PCI and <200 to 250 s for sheath removal.     

A strategy of using enoxaparin as adjunctive antithrombin therapy reduces death and recurrent myocardial infarction in patients who achieve early ST-segment resolution after fibrinolytic therapy: the ExTRACT-TIMI 25 ECG study.

AIMS: To determine the relationship between a strategy of enoxaparin (ENOX), early ST-segment resolution (STRes), and clinical outcomes on patients with ST-segment elevation myocardial infarction (STEMI) after fibrinolysis. METHODS AND RESULTS: Baseline and 180 min ECGs were analysed in 3208 of the 20 479 patients in the ExTRACT-TIMI 25 trial, which randomifzed patients with STEMI to ENOX vs. unfractionated heparin (UFH) as adjunctive therapy. STRes was defined as complete (70%), partial (30-70%), or none (<30%). There was no evidence for a difference in STRes between the groups assigned to the ENOX or UFH (median 69.4 vs. 67.2%; P = 0.13). Among patients with complete STRes (n = 1100), ENOX significantly reduced death or non-fatal recurrent MI at 30 days when compared with UFH (4.4 vs. 9.9%; OR(adj) 0.39; P < 0.001), whereas there was no difference in patients with only partial or no STRes [14.2 vs. 12.5%; OR(adj) 1.0; P = 0.98 (n = 368) and 16.2 vs. 15.9%; OR(adj) 1.0; P = 0.97 (n = 830), P for interaction = 0.008]. CONCLUSION: When compared with UFH, a strategy of ENOX significantly reduces death or non-fatal recurrent MI in patients who achieved complete STRes, but not in patients with less STRes. These data suggest that a strategy of ENOX improves outcomes by preventing re-occlusion in patients achieving initial successful reperfusion after fibrinolytic therapy rather than by facilitating initial reperfusion.     

Efficacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: results from the OASIS-5 trial.

OBJECTIVES: This study reports a prospectively planned analysis of patients with acute coronary syndrome who underwent early percutaneous coronary intervention (PCI) in the OASIS-5 (Fifth Organization to Assess Strategies in Ischemic Syndromes) trial. BACKGROUND: In the OASIS-5 trial, fondaparinux was similar to enoxaparin for short-term efficacy, but reduced major bleeding by one-half and 30-day mortality by 17%. METHODS: The OASIS-5 trial was a double-blind, randomized comparison of fondaparinux and enoxaparin in 20,078 patients with acute coronary syndrome. A total of 12,715 patients underwent heart catheterization during the initial hospitalization, and 6,238 patients underwent PCI. In the fondaparinux group, intravenous fondaparinux was given for PCI. In the enoxaparin group, no additional anticoagulant was given if PCI was <6 h from last subcutaneous dose, and additional intravenous unfractionated heparin (UFH) was given if PCI was >6 h. RESULTS: Fondaparinux compared with enoxaparin reduced major bleeding by more than one-half (2.4% vs. 5.1%, hazard ratio [HR] 0.46, p < 0.00001) at day 9, with similar rates of ischemic events, resulting in superior net clinical benefit (death, myocardial infarction, stroke, major bleeding: 8.2% vs. 10.4%, HR 0.78, p = 0.004). Fondaparinux reduced major bleeding 48 h after PCI irrespective of whether PCI was performed <6 h of the last enoxaparin dose (1.6% vs. 3.8%, HR 0.42, p < 0.0001) or >6 h when UFH was given (1.3% vs. 3.4%, HR 0.39, p < 0.0001). Catheter thrombus was more common in patients receiving fondaparinux (0.9%) than enoxaparin alone (0.4%), but was largely prevented by using UFH at the time of PCI, without any increase in bleeding. CONCLUSIONS: Upstream therapy with fondaparinux compared with upstream enoxaparin substantially reduces major bleeding while maintaining efficacy, resulting in superior net clinical benefit. The use of standard UFH in place of fondaparinux at the time of PCI seems to prevent angiographic complications, including catheter thrombus, without compromising the benefits of upstream fondaparinux.     

Impact of anticoagulation regimens on sheath management and bleeding in patients undergoing elective percutaneous coronary intervention in the STEEPLE trial

Objective: To evaluate the impact of sheath management on bleeding rates. Background: The procedural characteristics and anticoagulant regimen determine the frequency of postoperative bleeding complications following percutaneous coronary intervention (PCI). Methods: This subanalysis of the SafeTy and Efficacy of Enoxaparin in PCI patients, an internationaL randomized Evaluation (STEEPLE) trial evaluated the relative impact of enoxaparin or unfractionated heparin (UFH) on the rate of non‐coronary artery bypass graft‐related major and minor bleeding, according to sheath management procedures in 3,528 patients undergoing elective PCI with a femoral approach. Results: Sheaths were removed at a median time of 54 min with enoxaparin 0.5 mg/kg, compared with 3 hr 14 min with enoxaparin 0.75 mg/kg and 2 hr 24 min with UFH. Early sheath removal (within 30 min from the end of PCI) was associated with reduced bleeding in patients receiving 0.5 or 0.75 mg/kg enoxaparin compared with UFH (enoxaparin 0.5 mg/kg: 4.9% vs. 10.8%; P < 0.001; enoxaparin 0.75 mg/kg: 5.0% vs. 10.8%; P < 0.001). Compared with UFH, major and minor bleeding was halved when enoxaparin (0.5 mg/kg and 0.75 mg/kg) was used in combination with a closure device (4.4% and 5.3% vs. 10.5% with UFH) or smaller (<7 Fr) sheath sizes (4.9% and 6.0% vs. 9.3%). Conclusion: This analysis shows that early sheath removal can be performed safely following elective PCI in patients receiving enoxaparin. Enoxaparin use was associated with less major and minor bleeding compared with UFH, when either a closure device or a smaller sheath size was used. © 2009 Wiley‐Liss, Inc.     

Comparison of outcomes of percutaneous coronary interventions in patients of three age groups (<60, 60 to 80, and >80 years) (from the New York State Angioplasty Registry)

Octogenarians have been under-represented in percutaneous coronary intervention (PCI) trials despite an increase in referrals for PCI. As the United States population ages, the number of high-risk PCIs in the elderly will continue to increase. This study investigated the effect of age on short-term prognosis after PCI in 3 age groups. Using the 2000/2001 New York State Angioplasty Registry, we compared in-hospital mortality and major adverse cardiac events (MACEs; death, stroke, or coronary artery bypass grafting) in emergency and elective PCI cohorts across 3 age categories of patients: 10,964 patients who underwent emergency PCI (<60 years of age, n = 5,354; 60 to 80 years of age, n = 4,939; >80 years of age, n = 671) and 71,176 patients who underwent elective PCI (<60 years of age, n = 24,525; 60 to 80 years of age, n = 40,869; >80 years of age, n = 5,782). Patients were considered to have undergone an emergency PCI if they had an acute myocardial infarction within 24 hours, had thrombolytic therapy within 7 days, or presented with hemodynamic instability or shock. Elderly patients had more co-morbidities, including more extensive coronary atherosclerosis, hypertension, peripheral vascular disease, and renal insufficiency, and presented more frequently with hemodynamic instability or shock. In the emergency PCI group, in-hospital mortality (1.0% vs 4.1% vs 11.5%, p <0.05) and MACEs (1.6% vs 5.2% vs 13.1%, p <0.05) increased incrementally by age group. In the elective PCI group, rates of in-hospital complications were considerably lower, with an incremental increase in mortality (0.1% vs 0.4% vs 1.1%, p <0.05) and MACEs (0.4% vs 0.7% vs 1.6%, p <0.05). Age was strongly predictive of in-hospital mortality for emergency and elective PCI by multivariate analysis. In conclusion, elective PCI in the elderly has favorable outcome and acceptable short-term mortality in the stent era. Elderly patients, in particular octogenarians undergoing emergency PCI, have a substantially higher risk of in-hospital death.     

The impact of renal dysfunction on outcomes in the ExTRACT-TIMI 25 trial.

OBJECTIVES: The ExTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction 25) trial provided the opportunity to evaluate the impact of renal dysfunction on outcomes in patients with ST-segment elevation myocardial infarction (STEMI) and compare enoxaparin (ENOX) and unfractionated heparin (UFH). BACKGROUND: It is unclear how renal dysfunction influences the balance between benefit and risk of antithrombotic therapy. METHODS: In the ExTRACT-TIMI 25 trial, 20,479 patients were randomized to UFH or ENOX. A reduced ENOX dose was administered to patients age > or =75 years and those with an estimated creatinine clearance (CrCl) <30 ml/min. RESULTS: A powerful relationship was observed between the severity of renal dysfunction (per 10 ml/min decrement in CrCl) and death, stroke, intracranial hemorrhage, and major and minor bleeding (p < 0.001 for each). There was a progressive increase in the treatment benefit with ENOX on death or nonfatal myocardial infarction (p < 0.01) with better renal function. Net clinical benefit (death, nonfatal MI, or nonfatal major bleeding) was significantly superior with ENOX (p < 0.001) for patients with a CrCl >60 ml/min (79.1% of the study population). Major bleeding and intracranial hemorrhage did not differ for patients with preserved renal function (CrCl >90 ml/min), but in those with renal dysfunction there was a progressively greater increase in the risk of major and minor bleeding with ENOX. CONCLUSIONS: Enoxaparin was superior to UFH for the majority of subjects. With more severe renal dysfunction, the net clinical benefit between ENOX and UFH did not differ, despite the rise in adverse events in both treatment groups. Future studies should take renal dysfunction into account when assessing antithrombotic regimens.     

Novel Approaches for Preventing or Limiting Events (Naples) III Trial: Randomized Comparison of Bivalirudin Versus Unfractionated Heparin in Patients at Increased Risk of Bleeding Undergoing Transfemoral Elective Coronary Stenting

ObjectivesThis 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).BackgroundBivalirudin, a synthetic direct thrombin inhibitor, determines a significant decrease of in-hospital bleeding following PCI.MethodsThis 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.ResultsThe 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).ConclusionsThe 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)     

Safety and effectiveness of enoxaparin following fibrinolytic therapy: Results of the Acute Myocardial Infarction (AMI)-QUEBEC registry

BACKGROUND:

Previous randomized controlled trials and meta-analyses demonstrated the superior efficacy of enoxaparin (ENOX) over unfractionated heparin (UFH) in patients with ST segment elevation myocardial infarction (STEMI). The external validity of randomized controlled trials may be limited by selective inclusion of patients who are younger and healthier than the ‘real-life’ population.

OBJECTIVE:

To evaluate the safety and effectiveness of ENOX compared with UFH in unselected STEMI patients.

METHODS:

The safety and effectiveness of ENOX and UFH were compared in STEMI patients who received fibrinolytic therapy at 17 Quebec hospitals in 2003.

RESULTS:

A total of 498 STEMI patients received systemic anticoagulation, with ENOX and UFH administered in 114 and 384 patients, respectively. There were no differences in baseline characteristics between the two patient groups. The rates of in-hospital major adverse cardiac or cerebral events were 11.4% in the ENOX group compared with 14.0% in the UFH group (P=0.51). In-hospital death or nonfatal reinfarction occurred in 7.9% of patients who received ENOX compared with 9.9% of patients who received UFH (P=0.52). Major bleeding occurred in 4.4% of patients who received ENOX versus 6.0% in patients who received UFH (P=0.51).

INTERPRETATION:

There was no significant difference in the rates of in-hospital adverse events in the ENOX group compared with the UFH group, when used in the real-life context. Larger observational studies may further confirm the safety, effectiveness and optimal duration of the administration of ENOX in unselected STEMI patients treated with fibrinolysis.     

Outcomes of 1,090 consecutive, elective, nonselected percutaneous coronary interventions at a community hospital without onsite cardiac surgery

We evaluated the efficacy and safety of elective percutaneous coronary intervention (PCI) at a hospital without onsite cardiac surgery. A growing number of hospitals without onsite cardiac surgery perform elective PCI. Few hospitals have reported outcomes, despite controversy surrounding this practice. From August 2003 to December 2005, 1,090 elective PCI were performed at Saint Luke's South Hospital (SLS), a hospital without onsite cardiac surgery, for which the referral center is the Mid America Heart Institute (MAHI). The elective PCI program used experienced interventionalists, technicians, and nurses; a tested helicopter transport protocol; a well-equipped catheterization laboratory; and a quality assurance process. Baseline characteristics, procedural success, and adverse clinical outcomes were compared. Observed frequencies of in-hospital death, a combined end point of Q-wave myocardial infarction (MI)/emergency coronary artery bypass grafting (CABG) surgery, and vascular complications were compared with prediction models. SLS, with lower risk characteristics than MAHI, had unadjusted frequencies of procedural success (93% vs 94%, p = NS), Q-wave MI (0.3% vs 0.3%, p = NS), emergency CABG surgery (0.2% vs 0.03%, p = 0.09), vascular complications (0.6% vs 0.6%, p = NS), and in-hospital death (0.1% vs 0.8%, p = 0.002) that compared favorably with MAHI. Two patients transferred from SLS to MAHI for emergency CABG surgery without adverse effects. Fewer in-hospital deaths and vascular complications were observed at SLS than predicted by models. In conclusion, favorable clinical outcomes were achieved for elective PCI at a hospital without onsite cardiac surgery that used strict program requirements.     

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

Background: 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. Methods: 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 ≥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). Results: 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. Conclusion: Bivalirudin use seems to be as safe and effective as UFH in patients undergoing RA. (J Interven Cardiol 2010;23:223–229)     

Heparin or enoxaparin anticoagulation for primary percutaneous coronary intervention

Objectives : The aim of this study was to compare efficacy and safety outcomes among patients receiving enoxaparin or unfractionated heparin (UFH) while undergoing percutaneous coronary intervention (PCI) for ST‐segment elevation myocardial infarction (STEMI). Background : Primary PCI (pPCI) for ST elevation has traditionally been supported by UFH. The low molecular weight heparin enoxaparin may provide better outcomes when used for pPCI. Methods : Consecutive eligible patients (580) undergoing pPCI enrolled in the prospective electronic Pitié‐Salpêtrière registry of ischemic coronary syndromes (e‐PARIS) registry were grouped according to whether they received UFH or enoxaparin as the sole anticoagulant. Logistic regression modeling, propensity‐weighted adjustment, and sensitivity analyses were used to evaluate efficacy and safety endpoints for enoxaparin vs. UFH. Results : Enoxaparin was administered to 346 patients and UFH to 234 without ACT or anti‐Xa guided dose adjustment. PCI was performed through the radial artery in 90%, with frequent (75%) use of GPIIb/IIIa antagonists. Patients receiving enoxaparin were more likely to be therapeutically anticoagulated during the procedure (68% vs. 50%, P < 0.0001) and were less likely to experience death or recurrent myocardial infarction (MI) in hospital (adjusted OR 0.28 95% CI (0.12–0.68) or by 30 days (adjusted OR 0.35 95% CI 0.16–0.81). All cause mortality was also reduced in hospital (adjusted OR 0.32, 95% CI (0.12–0.85) and to 30 days (adjusted OR 0.40 95% CI 0.17–0.99). Other ischemic endpoints were similarly reduced with enoxaparin. Thrombolysis in myocardial infarction (TIMI) major bleeding events were numerically fewer among patients receiving enoxaparin (1.2% vs. 2.6%, P = 0.2). Conclusions : In patients with STEMI presenting for PCI, enoxaparin was associated with a reduction in all ischemic complications, more frequent therapeutic anticoagulation, and no increase in major bleeding when compared against unfractionated heparin. © 2010 Wiley‐Liss, Inc.     

Relation of preprocedural statin therapy to in-hospital procedural complications following percutaneous coronary interventions in patients with hyperlipidemia

We investigated whether the observed protective effect of hyperlipidemia is stronger in patients who take statins and, if so, whether that effect is likely due to patient characteristics associated with statin use. In-hospital complications and long-term outcomes of patients with hyperlipidemia (cholesterol level > or = 240 mg/dl) undergoing percutaneous coronary interventions (PCI) on statins (group Ia, n = 2,052) and not on statins (group Ib, n = 1,650) were compared with 726 patients with lower cholesterol levels (group II). Despite a higher prevalence of co-morbidities and worse angiographic characteristics in patients with hyperlipidemia, patients in group Ia had significantly lower in-hospital mortality (0% vs 2% in the other 2 groups, p < 0.001), a lower increase in the postprocedure creatine kinase-MB fraction (14% vs 27% in group Ib and 28% in group II, p < 0.001), and fewer PCI complications (15% vs 30% in groups Ib and II, p < 0.001). After adjustment, patients in group Ia had a significant decrease in complications (odds ratio 0.72, 95% confidence interval 0.65 to 0.92, p = 0.009). In contrast, those in group Ib had outcomes similar to those of patients with lower cholesterol. After application of propensity analysis to adjust for the likelihood of receiving statins based on clinical, angiographic, and procedural characteristics, group Ia had fewer in-hospital complications (odds ratio 0.75, 95% confidence interval 0.62 to 0.90, p = 0.002) and lower in-hospital mortality (odds ratio 0.32, 95% confidence interval 0.12 to 0.84, p = 0.021). After successful PCI, overall survival after dismissal and survival free of myocardial infarction and target vessel revascularization were similar. In conclusion, hyperlipidemia per se is not associated with lower in-hospital complications after PCI. The benefit is largely limited to patients on statin treatment.     

Bivalirudin versus Unfractionated Heparin during Percutaneous Coronary Intervention in Patients at High Risk for Bleeding

Low/medium-bleeding-risk populations undergoing percutaneous coronary intervention (PCI) show significantly less bleeding with bivalirudin (BIV) than with unfractionated heparin (UFH), but this has not been established for high-risk patients. We performed a randomized double-blind prospective trial comparing efficacy and safety of BIV versus UFH combined with dual antiplatelet therapy during PCI among 100 high-risk patients with non-ST elevation myocardial infarction (NSTEMI) or angina pectoris. The baseline characteristics were similar in both treatment arms. A radial approach was used in 84% of patients with a higher rate in the BIV group (90 vs. 78%, p < 0.05). Study end points were: major and minor bleeding, port-of-entry complications, major adverse cardiac events (MACE) in-hospital, and at long-term follow-up. There was one case of major gastrointestinal bleeding in the BIV group and 7% minor bleeding complications in both categories. Rate of periprocedural myocardial infarction (PPMI) in the BIV group was twice that in the UFH group (20 vs. 10%, p < 0.16). In-hospital MACE rate was higher in BIV patients as well (12 vs. 2%, p = 0.1). By univariate analysis, the femoral approach was the predictor of PPMI and in-hospital MACE. In a multivariate model, the independent predictor of PPMI was previous MI (odds ratio, 7.7; p < 0.0158). PPMI was 49.7 times more likely with the femoral approach plus BIV than the nonfemoral approach plus UFH (p < 0.0021). At 41.5 ± 14 months'' follow-up, end points did not significantly differ between the groups. In patients at high risk for bleeding undergoing PCI, BIV was not superior to UFH for bleeding complications, and early and late clinical outcomes.