Glycoprotein IIb/IIIa Inhibitors Use Research Articles

Anticoagulation for percutaneous coronary intervention: a contemporary review.

Optimal anticoagulation is needed to prevent ischemic complications during percutaneous coronary interventions (PCIs). The efficacy and safety of new anticoagulants to support PCI in different clinical scenarios have been evaluated in large clinical trials. This review summarizes the major issues and current practices for anticoagulation during PCI. It is known that thrombotic events during PCI correlate with poor prognosis. However, the prognostic impact of bleeding is similar or even worse compared with ischemic complications. Therefore, the use of more predictable anticoagulants and safe practices in the catheterization laboratory to balance ischemia and bleeding is an important goal. Mindful of this notion, new anticoagulants with a safer profile, such as bivalirudin, have become popular to avoid bleeding. However, this paradigm shift has resulted in increased rates of acute stent thrombosis after primary PCI. Individual factors associated with increased bleeding risk should be considered in the choice of anticoagulants during PCI. It is now known that the higher bleeding risk observed with heparin-based regimens can be attributed to excessive doses or concomitant use of glycoprotein IIbIIIa inhibitors. In addition to the right anticoagulant choice, operators can avoid bleeding by implementing transradial access and ultrasound-guided and fluoroscopic-guided vascular access.

Bivalirudin versus heparin in patients treated with percutaneous coronary intervention: a meta-analysis of randomised trials.

Current recommendations on the use of bivalirudin in patients treated with percutaneous coronary intervention (PCI) are mostly based on trials comparing bivalirudin versus heparin plus planned glycoprotein IIb/IIIa inhibitor (GPI). Whether bivalirudin is also superior to heparin alone is still not well established. This meta-analysis investigates the efficacy and safety of bivalirudin versus heparin in patients treated with PCI without planned use of GPI. Scientific databases and websites were searched for randomised controlled trials. The primary efficacy and safety outcomes were the 30-day incidence of death and major bleeding, respectively. The secondary outcomes were the 30-day incidence of myocardial infarction (MI), definite stent thrombosis (ST), urgent target vessel revascularisation (TVR), and overall death at the longest available follow-up. Odds ratio (OR) and 95% confidence interval (95% CI) served as summary statistics. Ten trials were identified including a total of 18,065 PCI patients randomised to bivalirudin (n=9,033) versus heparin (n=9,032). At 30 days, bivalirudin versus heparin showed a comparable risk of death (1.09 [0.83-1.41], p=0.54), and MI (1.10 [0.83-1.46], p=0.50) with a trend towards a higher risk of urgent TVR (1.37 [0.96-1.96], p=0.08). The risk of major bleeding was lower with bivalirudin (0.57 [0.40-0.80], p=0.001) and the bleeding reduction was more evident when high doses of heparin were used as comparator (p for interaction <0.001). The risk of definite ST (2.09 [1.26-3.47], p=0.005) and, in particular, the risk of acute ST (3.48 [1.66-7.28], p<0.001) was increased by bivalirudin. Patients undergoing PCI randomised to therapy with either bivalirudin or heparin display a similar mortality. Bivalirudin as compared to heparin appears to reduce the risk of major bleeding at the expense of a higher risk of acute ST.

Bivalirudin in stable angina and acute coronary syndromes.

A parenteral anticoagulant is indicated in patients with acute coronary syndromes. Which anticoagulant should be preferred in each setting is not clearly established. Bivalirudin administration was considered in acute coronary syndromes after several clinical trials showed decreased bleeding risk with its use compared with the association of unfractionated heparin (UFH) with glycoprotein IIb/IIIa inhibitors (GPIs). Most recent data demonstrate that the bleeding benefit identified in the previous studies was not due to bivalirudin's properties but to higher bleeding incidence in the comparator arm due to the disproportional use of GPIs with heparin. This paper reviews clinical evidence on bivalirudin as anticoagulant in stable angina and acute coronary syndromes.

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.

Abstract 16476: Safety Profile of Bivalirudin in the Treatment of ST-Segment Elevation Myocardial Infarction Patients in Clinical Practice - Results From the Bremen STEMI Registry

Introduction: Previous studies demonstrated that treatment of patients (pts) being affected by ST-segment elevation myocardial infarction (STEMI) with bivalirudin (biv) instead of heparin (hep) reduced rates of major bleedings. Results regarding a reduction in all-cause mortality are inconclusive, stent thromboses however were slightly increased. Real world data in pts with STEMI treated with biv in the era of new anti-thrombotic treatment are still spare. The aim of this study was to evaluate safety of biv for all-comers. Methods: All pts with STEMI from the metropolitan area of Bremen (Germany) are admitted to the Bremen heart center and documented in the Bremen STEMI-registry (BSR) since 2006. In May 2013 we adapted our anticoagulation strategy to the current guidelines from hep with glycoprotein IIb/IIIa inhibitors (GPI) to biv with provisional use of GPI. Pts receiving biv were compared to all pts until April 2013 in the BSR without chronic renal failure. Results: Baseline and interventional characteristics of 530 consecutive pts treated with biv and 5197 pts treated with hep are shown in table 1. Despite a higher portion of pts after resuscitation (10.3% vs 8.6%; p&lt;0.01) and a higher incidence of Killip class 3 or 4 (15% vs 8%; p&lt;0.001) in the biv group inhospital all-cause mortality showed no difference (biv: 6.8% vs hep: 7.3%, p=0.66). However pts treated with biv demonstrated highly significant lower bleeding rates (TIMI major/minor bleedings: 0.8% vs 3.7%, p&lt;.01). Stent-thromboses showed a trend towards an increased event rate with biv (1.3%, 7pts vs 1.0%, 52pts, p=0.07). Conclusions: In one of the largest all-comers registries treatment with biv was associated with significantly lower minor and major bleedings. There is only a trend for a higher rate of stent thromboses in the biv group. Therefore, data from our all-comers registry support the beneficial safety profile of biv observed in clinical studies.

TCT-825 Bleeding events are reduced and survival improved by use of radial access during primary percutaneous coronary intervention for patients receiving glycoprotein inhibitors

access during primary percutaneous coronary intervention for patients receiving glycoprotein inhibitors Control Number: 2917 Submission Type: Abstract Presentation Format: Poster Only New Device/Innovation: No Author(s): Adam J Brown, Nikil K Rajani, Liam M McCormick, Stephen P Hoole, Nick E West Institution(s): University of Cambridge, Cambridge, United Kingdom, Papworth Hospital, Cambridge, United Kingdom Presenter Poster: Dr Adam J Brown, MB BChir View Disclosure University of Cambridge Background: Use of glycoprotein IIb/IIIa inhibitors (GPI) during primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) is known to improve myocardial perfusion and reduce further ischemic events, but is associated with an increase in bleeding risk. Performing PPCI via radial access (rPPCI) is thought to reduce post-procedural bleeding complications and may improve overall survival. We sought to assess whether rPPCI is associated with improved outcomes in patients receiving GPI at our institution. Methods: Consecutive patients undergoing PPCI for STEMI over a four-year period were included. All patients were preloaded with 600mg clopidogrel and 300mg aspirin en-route to PPCI. Interventional strategy and GPI use were left to operator discretion. Patient data and outcome measures were obtained by interrogation of notes and national databases. Bleeding complications were categorized using Bleeding Academic Research Consortium (BARC) definitions. Results: 2,019 patients were included in the analysis (mean age 64.2±12.4yrs, 75.9% male), with 863 receiving GPI. Patients that received GPI were younger (62.7±11.8yrs vs. 64.8±12.6yrs, p< 0.001), more likely to be male (80.5% vs. 73.9%, p< 0.001) but had a higher incidence of cardiogenic shock (5.6% vs. 2.7%, p=0.002). Other baseline demographics were similar. Overall, BARC defined bleeding was more prevalent in those receiving GPI (BARC ≥2 3.0% vs. 0.7%, p< 0.001; BARC ≥3 2.6% vs. 0.2%, p< 0.001). However, patients undergoing rPPCI with GPI had lower bleeding rates when compared with femoral access (0.8% vs. 3.7%, p=0.05). For patients receiving GPI, rPPCI resulted in a significant improvement in 1-year survival (99.2% vs. 93.5%, p=0.01; OR 0.12, 95%CI 0.02-0.87, p=0.04). However, in patients not receiving GPI, no survival benefit for rPPCI was observed (94.4% vs. 93.7%, p=0.70; OR 0.87, 95%CI 0.44-1.71, p=0.69). Conclusions: rPPCI results in lower rates of bleeding and improved survival in patients receiving GPI during PPCI. rPPCI should be considered in patient groups where subsequent use of GPI is likely. CORONARY: STEMI and NSTEMI

Efficacy of Pre-Hospital Use of Glycoprotein IIb/IIIa Inhibitors in ST-Segment Elevation Myocardial Infarction Before Mechanical Reperfusion in a Rapid-Transfer Network (from the Acute Myocardial Infarction Registry of Brittany)

Previous studies investigating prehospital use of glycoprotein IIb/IIIa inhibitors (GPIs) in patients with ST-segment elevation myocardial infarction reached conflicting conclusions. The benefit of this strategy in addition to in-ambulance loading of dual-antiplatelet therapy remains controversial. The aim of this study was to analyze data from a prospective registry of patients with ST-segment elevation myocardial infarctions admitted <24 hours after symptom onset (July 2006 to May 2012). A total of 2,052 patients managed in a physician-staffed mobile intensive care unit (MICU)<12 hours after symptom onset and scheduled for primary percutaneous coronary intervention (PPCI) were retrospectively included. Patients who received GPIs in the MICU were compared with those who did not. The primary end point was infarct-related artery patency, defined as pre-PPCI Thrombolysis In Myocardial Infarction (TIMI) flow grade 3. GPIs were administered in the MICU to 737 patients (36%), including 430<2 hours after symptom onset, and 1,315 patients (64%) did not received prehospital GPIs. Pre-PPCI TIMI flow grade 3 rate was lower in patients treated in the MICU (17.2% vs 21.3%, p=0.03) because of patients treated >2 hours after symptom onset, of whom only 12.7% reached the primary end point. There was no significant difference between groups in the rate of in-hospital major adverse cardiac events. In conclusion, prehospital GPI use in patients with ST-segment elevation myocardial infarctions<12 hours after symptom onset scheduled for PPCI neither improved pre-PPCI infarct-related artery patency nor reduced in-hospital major adverse cardiac events.

Direct stenting is an independent predictor of improved survival in patients undergoing primary percutaneous coronary intervention for ST elevation myocardial infarction

Randomised trials have shown that direct stenting (DS) is associated with improved markers of reperfusion during primary percutaneous coronary intervention (PPCI) for ST elevation myocardial infarction (STEMI). However, data evaluating its impact on long-term clinical outcomes are lacking. We set out to evaluate the effect of DS on mortality in a contemporary population of patients undergoing PPCI for STEMI. Consecutive patients undergoing PPCI for STEMI at two high-volume UK heart attack centres between September 2008- December 2010 (n=1562) were included in the analysis. Local databases were analysed for patient demographics, as well as details on PPCI strategy, including use of DS versus predilatation (PD) followed by stenting, manual thrombus aspiration (MT) and glycoprotein IIb/IIIa inhibitors (GPIs). National databases were interrogated for in-hospital, 30-day and one-year mortality. To determine the impact of PPCI strategy on one-year survival, multivariate logistic analysis was performed. Altogether 489 patients underwent DS (31.3%) and 1073 (68.7%) received PD prior to stenting. Patients receiving DS had reduced mortality at 30 days (2.04 versus 4.66%, p=0.01) and one year (3.27 versus 8.48%, p=0.0001). After multivariate adjustment, PD remained an independent predictor of one-year mortality (odds ratio 2.42, 95% confidence interval 1.08-5.45, p=0.032) along with age, cardiogenic shock, number of diseased vessels, and left main or proximal left anterior descending artery intervention. However, neither GPI use nor MT improved survival in either univariate or multivariate analyses. In a contemporary, unselected population of patients undergoing PPCI for STEMI, DS - when compared with stenting after PD - is independently predictive of improved 30-day and one-year survival.

Glycoprotein IIb-IIIa inhibitors for acute ischaemic stroke

Glycoprotein (GP) IIb-IIIa inhibitors are antiplatelet agents that act by antagonising GP IIb-IIIa receptors on the platelet surface and block the final common pathway to platelet aggregation by preventing the binding of fibrinogen molecules that form bridges between adjacent platelets. Thus, GP IIb-IIIa inhibitors could favour endogenous thrombolysis by reducing thrombus growth and preventing thrombus re-formation through competitive inhibition with fibrinogen and, due to their mechanism of action, are likely to have a more profound antiplatelet effect with more rapid onset than conventional antiplatelet agents, such as aspirin or clopidogrel. Currently used in clinical practice for the treatment of individuals with acute coronary syndromes and during coronary angioplasty, GP IIb-IIIa inhibitors could also be useful for the treatment of people with acute ischaemic stroke. To assess the use of GP IIb-IIIa inhibitors in people with acute ischaemic stroke to evaluate whether such treatments (1) reduce the proportion of patients who die or remain dependent, and (2) are sufficiently safe for general use. We wished to examine the effects GP IIb-IIIa inhibitors alone or in combination with thrombolytic agents. We searched the Cochrane Stroke Group trials register (last searched 10 June 2013), MEDLINE (1966 to June 2013), EMBASE (1980 to June 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 5, 2013), and major ongoing clinical trials registers (June 2013). We also searched reference lists and contacted trial authors and pharmaceutical companies. We aimed to analyse unconfounded randomised controlled trials (RCTs) of GP IIb-IIIa inhibitors in the treatment of people with acute ischaemic stroke. Only individuals who started treatment within six hours of stroke onset were included. We independently selected trials for inclusion, assessed trial quality and extracted the data. We included four trials involving 1365 participants. Three trials compared the intravenous GP IIb-IIIa inhibitor Abciximab with intravenous placebo (1215 participants) and one trial compared the intravenous GP IIb-IIIa inhibitor Tirofiban with intravenous aspirin (150 participants). Treatment with either of these GP IIb-IIIa inhibitors did not significantly reduce long-term death or dependency (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.77 to 1.22, for the comparison between Abciximab and placebo; OR 1.00, 95% CI 0.52 to 1.92, for the comparison between Tirofiban and aspirin) and had no effect on deaths from all causes (OR 1.08, 95% CI 0.77 to 1.53, for the comparison between Abciximab and placebo; OR 1.00, 95% CI 0.35 to 2.82, for the comparison between Tirofiban and aspirin). Abciximab was associated with a significant increase in symptomatic intracranial haemorrhage (OR 4.6, 95% CI 2.01 to 10.54) and with a non-significant increase in major extracranial haemorrhage (OR 1.81, 95% CI 0.96 to 3.41), whereas the only small trial comparing Tirofiban with aspirin showed no increased risk of bleeding complications with Tirofiban (OR 0.32, 95% CI 0.03 to 3.19, for symptomatic intracranial haemorrhage; OR 3.04, 95% CI 0.12 to 75.83, for major extracranial haemorrhages). There was no significant inconsistency across the studies. The available trial evidence showed that, for individuals with acute ischaemic stroke, GP IIb-IIIa inhibitors are associated with a significant risk of intracranial haemorrhage with no evidence of any reduction in death or disability in survivors. These data do not support their routine use in clinical practice. The conclusion is driven by trials of Abciximab, which contributed 89% of the total number of study participants considered.

The impact of radial access on in-hospital mortality of patients undergoing primary PCI. Data from the Portuguese interventional cardiology registry

Aims: Radial access was associated with a significant reduction in major bleeding, compared to femoral access, in the treatment of ST segment Elevation Myocardial Infarction (STEMI). It is not yet clear its impact on in-hospital mortality. The aims of this study are to compare in-hospital mortality in patients undergoing primary PCI via radial access or femoral access, based on the Portuguese Interventional Cardiology Registry (PICR), and evaluate the interaction with the use of glycoprotein IIbIIIa (GP IIbIIIa) inhibitors. Methods and results: 6559 consecutive pts with STEMI undergoing primary PCI prospectively included in the PICR from Jan/2007 to Dec/2012. Radial access was used in 1384 pts (21%) and femoral access in 5175 (81.9%). We compared demographic and clinical variables between the 2 groups. Independent predictors of in-hospital mortality were identified by multivariate analysis. The interaction with the use of GP IIbIIIa inhibitors was also evaluated. In-hospital mortality occurred in 3.3% of pts undergoing primary PCI via femoral access and in 0.8% of pts undergoing primary PCI via radial access (p <0.01). After multivariate analysis, radial access was an independent predictor of in-hospital mortality (OR 0,3; IC 0,125-0,699, p=0,006). Other predictors identified in the model were age ≥65 years (OR 3.1, IC 1.940-4.816, p<0.001), history of heart failure (OR 3.0, IC 1.144-7.910, p=0.026), history of peripheral artery disease (OR 8.5, IC 4.693-15.472, p<0.001), history of smoking (OR 0.5, IC 0.332-0.862, p=0.010), hemodynamic support (OR 8.9, IC 5.622-14.194, p<0.001), left main PCI (OR 4.7, IC 2.246-9.834, p<0.001), right coronary artery PCI (OR 1.7, IC 1.182-2.559, p=0.005). The benefit of choosing radial access over femoral access was independent from Gp IIbIIIa inhibitors use (p for interaction NS). Conclusion: In this population of STEMI pts undergoing primary PCI, radial access was associated to a lower in-hospital mortality regardless the use of Gp IIbIIIa inhibitors.

Pharmacodynamic response to clopidogrel and outcomes in the ARCTIC randomized trial

Background: The ARCTIC trial failed to demonstrate improvements in outcomes with platelet-function monitoring and treatment adjustment for PCI Aim: To analyze clinical outcome according to clopidogrel pharmacodynamic (PD) response using the VerifyNow assay just before PCI. Methods: Among patients randomized in the monitoring arm of the ARCTIC trial (n=1213), 419 (34.5%) had high on-treatment platelet reactivity (HPR patients) before PCI and underwent treatment adjustment. We compared the occurrence of the composite primary end point (PEP) of death, MI, stent thrombosis, stroke, or urgent revascularization 1 year after stent implantation in patients presenting HPR to clopidogrel before PCI (n=419), non-HPR patients (n=794) and patients randomized in the conventional arm without PD evaluation (n=1227). Safety bleeding endpoints were also analyzed. Results: HPR to clopidogrel was associated with higher age, female gender, higher bodyweight, diabetes and PPI use (all p <0.05). HPR patients underwent more aggressive antiplatelet strategy than non-HPR patients due to the study protocol, with significant more frequent use of GPIIbIIIa inhibitors (79.2% vs. 5.2%, p<0.01), clopidogrel LD (80.2% vs 3.5%, p<0.001) or prasugrel LD before PCI (3.3% vs 0.1%, p<0.001) as compared with non-HPR patients. High clopidogrel MD (150mg or more) (82.6% vs. 32.1%, p<0.001) or prasugrel 10mg MD (18.6% vs. 4.4%%, p<0.001) was also significantly more frequent in HPR patients at discharge as compared with non-HPR patients. The PEP occurred in 34.6% of the patients with HPR who underwent treatment adjustment, in 34.6% of the non-HPR patients (HR 0.97 [0.80; 1.19], p= 0.8) and in 31.1% of the patients randomized in the conventional arm (HR 1.11 [0.91; 1.34] p= 0.31 and 1.14 [0.97; 1.33], p=0.11) for both comparisons). Despite using a much stronger antiplatelet strategies in HPR patients, major bleeding did not differ between HPR patients as compared with non-HPR patients (2.6% vs. 2.1%, respectively, HR 1.19 [0.56; 2.54] p= 0.65) or from patients randomized in the conventional arm of the ARCTIC study (2.6% vs. 3.3%, HR 0.78 [0.40; 1.53] p= 0.47). Conclusion: In ARCTIC, the prognosis of patients with HPR before PCI leading to antiplatelet therapy adjustment did not differ from patients without HPR and without adjustment of therapy. Although, this subgroup analysis comforts the main finding of the study, the hypothesis that tailoring might have corrected impaired prognosis associated with HPR in this high-risk group of patients cannot be eliminated by the ARCTIC study.

Glycoprotein IIb/IIIa inhibitors with or without thienopyridine pretreatment improve outcomes after primary percutaneous coronary intervention in high‐risk patients with ST elevation myocardial infarction—a meta‐regression of randomized controlled trials

Recent studies have casted a doubt on usefulness of routine glycoprotein IIb/IIIA inhibitors (GPI) in patients, pretreated with aspirin and clopidogrel, undergoing primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI). We aimed to investigate the effect of relevant factors, particularly thienopyridine pretreatment, on clinical benefit from GPI in randomized controlled trials (RCT). We searched electronic databases for RCT comparing GPI to control in patients with STEMI undergoing primary PCI. Relevant study covariates and clinical outcomes were extracted. A random effect cumulative and subgroup analyses (thienopyridine non-pretreated studies vs. pretreated studies) were performed. A weighted random effect meta-regression to determine the effect of thienopyridine pretreatment, enrollment year, control group mortality, and ischemic time on mortality benefit from GPI use was conducted. Twenty studies (9 non-pretreated, 11 pretreated) with a total of 7,414 patients (3,811 GPI, 3,603 control) were included. GPI use reduces mortality (risk ratio, RR = 0.75 95% confidence interval (CI) 0.57-0.97, P = 0.03), target vessel revascularization (TVR) (RR = 0.63, 95% CI 0.50-0.80, P = 0.0002), but not reinfarction (RR = 0.66, 95% CI 0.44-1.0, P = 0.05) at 30 days. There was no effect of thienopyridine pretreatment on reduction in mortality (P = 0.39), reinfarction (P = 0.46), or TVR (P = 0.95) in subgroup analysis. Meta-regression analyses showed significant effect of control group mortality risk (B = -12.15, P = 0.034) but not of thienopyridine pretreatment, enrollment year or control group ischemic time on mortality reduction from GPI use. The benefit from GPI use in primary PCI for STEMI appears to depend on mortality risk, and not on thienopyridine pretreatment.

Abstract 19450: Manual Thrombus Aspiration is not Associated with Reduction in Infarct Size Assessed by Delayed Enhancement MDCT

Objective: We sought to assess whether manual thrombus aspiration could reduce infarct size in patients with acute ST-elevation myocardial infarction (MI) undergoing primary percutaneous coronary intervention (PCI). Background: The efficacy of manual thrombus aspiration during primary PCI for acute MI remains controversial. Methods: Between April 2009 and Mar 2011, 86 consecutive patients presenting with first acute STEMI (Killip≤II) within 12 hours after the symptom onset were randomized to manual thrombus aspiration (group I, N=44) or conventional PCI without thrombus aspiration (group II, N=42). The use of glycoprotein IIb/IIIa inhibitor (GPI) was left to the discretion of the operator. All patients received aspirin 300 mg and clopidogrel 600 mg before PCI and underwent delayed enhancement (DE) multi-detector computed tomography (MDCT) immediately after PCI without injection of an additional contrast media for assessment of infarct size, determined as the total volume of myocardium showing DE. DE MDCT was repeated at 2 months after PCI. The primary endpoint was infarct size reduction at 2 months. Results: Baseline clinical characteristics and angiographic findings were similar between the 2 groups. There were no differences between group I and II in symptom-to-door time, door-to-balloon time, PCI-to-MDCT time, Pre-PCI TIMI 0/1, post-PCI TIMI 3, or the use of GPI. Markers of myocardial reperfusion showed better outcome in group I but without statistical difference: ST-resolution rate &gt;70% (74% vs. 65%), myocardial blush grade 3 (88% vs. 68%), and corrected TIMI frame count &lt;28 (31% vs. 24%). Initial infarct size determined by DE MDCT and left ventricular ejection fraction (LVEF) by 2-dimensional echocardiography were similar between group I and II (17±18 mL vs. 22±23 mL and 58±11% vs. 55±10%, respectively). At 2 months, there was no difference in infarct size and left ventricular ejection fraction between the groups: 14±10 mL vs. 17±12 mL and 62±12% vs. 60±2%, respectively. No adverse cardiac events occurred in either group during the 2-month clinical follow-up. Conclusion: Manual thrombus aspiration was not associated with reduction in infarct size in patients with acute ST-elevation MI undergoing primary percutaneous coronary intervention.

Bivalirudin versus unfractionated heparin in percutaneous coronary interventions of patients having received initial fondaparinux treatment: a propensity matched study

Fondaparinux is an indirect, Factor Xa inhibitor that requires co-administration of another anticoagulant with anti-Factor IIa activity for percutaneous coronary intervention (PCI) per guideline recommendations. In this setting, the use of bivalirudin, a direct Factor IIa inhibitor, is not well established. Using the Premier hospital database, we identified 971 patients who underwent elective or urgent PCI after receiving fondaparinux as the initial anticoagulant. They were treated with either bivalirudin ± glycoprotein IIb/IIIa inhibitor (GPI) (Group A=618) or unfractionated heparin (UFH) ± GPI (Group B=353) during PCI. A 2:1 propensity score matching (PSM) process was performed to control for patient and hospital level characteristics. The primary endpoints were to determine in-hospital death, bleeding and post-PCI length of stay (LOS) between treatment groups. After PSM, 512 matched patients were analysed (Group A=348 and Group B=174). In-hospital death was 1.4% in Group A vs. 2.9% in Group B (p=0.26). Clinically apparent bleeding occurred in 4.0% of Group A vs. 9.2% of Group B patients (p<0.02). Clinically apparent bleeding requiring transfusion was lower in Group A patients (0.6% vs. 2.9%; p=0.04). Post-PCI LOS was 1.9 ± 3.8 days for Group A and 2.4 ± 5.8 days for Group B (p=0.36). GPI use during PCI occurred in 9.2% of Group A vs. 44.8% of Group B patients (p<0.0001). After initial administration of fondaparinux, a bivalirudin-based strategy for PCI is associated with significantly reduced bleeding, with similar mortality and post-PCI LOS when compared with an UFH-based strategy.

Comparative Effectiveness Analysis of Anticoagulant Strategies in a Large Observational Database of Percutaneous Coronary Interventions

Percutaneous coronary intervention (PCI) is the most commonly used procedure for coronary revascularization. There are multiple adjuvant anticoagulation strategies available. In this era of cost containment, we performed a comparative effectiveness analysis of clinical outcomes and cost of the major anticoagulant strategies across all types of PCI procedures in a large observational database. A retrospective, comparative effectiveness analysis of the Premier observational database was conducted to determine the impact of anticoagulant treatment on outcomes. Multiple linear regression and logistic regression models were used to assess the association of initial antithrombotic treatment with outcomes while controlling for other factors. A total of 458,448 inpatient PCI procedures with known antithrombotic regimen from 299 hospitals between January 1, 2004 and March 31, 2008 were identified. Compared to patients treated with heparin plus glycoprotein IIb/IIIa inhibitor (GPI), bivalirudin was associated with a 41% relative risk reduction (RRR) for inpatient mortality, a 44% RRR for clinically apparent bleeding, and a 37% RRR for any transfusion. Furthermore, treatment with bivalirudin alone resulted in a cost savings of $976 per case. Similar results were seen between bivalirudin and heparin in all end-points. Combined use of both bivalirudin and GPI substantially attenuated the cost benefits demonstrated with bivalirudin alone. Bivalirudin use was associated with both improved clinical outcomes and decreased hospital costs in this large "real-world" database. To our knowledge, this study is the first to demonstrate the ideal comparative effectiveness end-point of both improved clinical outcomes with decreased costs in PCI.

Efficacy and Safety of Unfractionated Heparin Plus Glycoprotein IIb/IIIa Inhibitors During Revascularization for an Acute Coronary Syndrome: A Meta‐Analysis of Randomized Trials Performed With Stents and Thienopyridines

Early studies of glycoprotein IIb/IIIa inhibitors (GPIs) demonstrated benefit during percutaneous coronary intervention for acute coronary syndromes (ACS). Since their introduction, the magnitude of benefit of GPIs has become unclear. We hypothesized that adding a GPI to unfractionated heparin in ACS patients treated with stents and thienopyridines is beneficial. We searched the MEDLINE, Cochrane, and clinicaltrials.gov databases for randomized clinical trials that studied the use of GPIs during ACS. We required that patients be randomly assigned to unfractionated heparin plus a GPI versus unfractionated heparin plus placebo (or control). Additional inclusion criteria included the use of coronary stents and periprocedural thienopyridines. Outcomes were assessed at 30 days. Random effects DerSimonian-Laird summary risk ratios (RR) and 95% confidence intervals (CIs) were constructed. Sixteen studies with 7611 patients were included. Myocardial infarction was 3.1% with GPI versus 4.4% with control (RR = 0.74; 95% CI, 0.59-0.94, P = 0.014); revascularization, 1.7% versus 2.7% (RR = 0.64; 95% CI, 0.46-0.89, P = 0.008); major bleeding, 2.5% versus 2.1% (RR = 1.21; 95% CI, 0.89-1.63, P = 0.22); minor bleeding, 5.5% versus 4.1% (RR = 1.37; 95% CI, 1.06-1.78, P = 0.016); and mortality, 2.2% versus 2.9% (RR = 0.79; 95% CI, 0.59-1.06, P = 0.12), respectively. Among ACS patients treated with stents and thienopyridines, GPIs were associated with reduced myocardial infarction and revascularization. Minor, but not major bleeding was increased with GPIs. Mortality was similar between the groups. © 2011 Wiley Periodicals, Inc. Supporting information may be found in the online version of this article This work was supported by an unrestricted grant from the Florida Heart Research Institute, which had no role in the study design, data collection, analysis, or interpretation, manuscript writing, or decision to proceed with publication. Anthony A Bavry has received research support from Novartis Pharmaceuticals and serves as a contractor for American College of Cardiology Cardiosource. The other authors have no funding, financial relationships, or conflicts of interest to disclose.

Long-term outcomes after coronary bare-metal-stent and drug-eluting-stent implantations

Drug-eluting stents (DESs) have been reported to be more efficacious compared with bare-metal stents (BMSs) in reducing the need for target vessel revascularization (TVR). However, the long-term benefits for patients with diabetes with small vessel disease are less certain. We aim to determine the clinical outcome of patients with diabetes with diffuse small vessel coronary artery disease who undergo percutaneous coronary intervention. This is a single-center prospective registry of all patients with diabetes with target lesions implanted with stents that were 2.25 mm or less in diameter and approximately 20 mm in total stent length between January 2002 and October 2008. Primary outcome was combined major adverse cardiovascular events: death, nonfatal myocardial infarction and TVR up to 5 years. Outcomes were adjusted for age, sex and cardiovascular risk factors. There were 544 patients (63% males, mean age 62±10 years) with 1010 lesions that were followed up for a mean duration of 3±2 years. Two hundred and thirty-nine patients (439 lesions) received BMS whereas 305 (571 lesions) received DES. DES lesions were longer (mean length 23.3±6.96 vs. 17.8±5.02 mm, P<0.001) than BMS lesions. Procedural success was similar for BMS and DES patients (86.2 vs. 86.6%, P=0.90). DES patients had less TVR at 6 months [3.9 vs. 9.2%, odds ratio (OR): 4.90, 95% confidence interval (CI): 1.53-15.65, P=0.007], 1 year (1 vs. 3.8%, OR: 8.01, 95% CI: 1.25-51.10, P=0.028) and 3 years (13.8 vs. 18.0%, OR: 5.50, 95% CI: 3.74-8.13, P=0.043). By 5 years, the primary outcome was lower in DES patients (21.6 vs. 28%, OR: 1.79, 95% CI: 1.14-2.80, P=0.011). Independent predictors of TVR at 6 months were above or equal to 59 years of age (OR: 0.95, 95% CI: 0.90-1.00, P=0.032) and use of glycoprotein-IIbIIIa inhibitors (OR: 0.02, 95% CI: 0.001-0.50, P=0.018). Stent length was not a significant predictor of TVR. Our observational analysis suggests that DES seems to have short-term and mid-term advantages over BMS in reducing TVR and overall major adverse cardiovascular events. Percutaneous coronary intervention with DES may be considered as an option in these patients with limited revascularization options.

Economic Impact of Switching to Bivalirudin for a Primary Percutaneous Coronary Intervention in a US Hospital

Background: The addition of glycoprotein IIb/IIIa inhibitors (GPIs) to heparin in percutaneous coronary intervention (PCI) procedures has been demonstrated to reduce ischemic complications; however, GPI use is known to increase the risk of bleeding events, which are linked to increased mortality, longer hospital length of stay, greater medical resource utilization, and increased costs. New antithrombotic therapies have the potential to improve clinical outcomes and decrease costs. The Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) study of bivalirudin demonstrated significantly reduced clinical event rates (mortality and bleeding) compared with an unfractionated heparin (UFH) + GPI regimen. Objective: The potential clinical and economic value of implementing a bivalirudin-based strategy for ST-segment elevation myocardial infarction (STEMI) patients receiving primary PCI (PPCI) is compared with current UFH + GPI-based practice from a US hospital perspective. Methods: A budget impact model was developed to compare treatment of STEMI patients undergoing PPCI with a bivalirudin- or UFH + GPI-based strategy. Clinical data for the model were derived from the HORIZONS-AMI trial, and included 30-day event rates for major complications (eg, protocol bleeding, Q-wave MI, repeat PCI, and coronary artery bypass graft procedures). United States cost data and clinical practice data were derived from a Premier Perspective™ database analysis and published sources. Results: Overall, average procedure costs per UFH + GPI-treated patient were $18 561. Treating patients with bivalirudin (incorporating 7.2% provisional GPI use per HORIZONS-AMI) may save $1690 per patient (average procedural cost, $16 872). In extrapolating these benefits to the American College of Cardiology/American Heart Association recommended institutional minimum of 36 PPCIs annually, 1 major bleeding event (3.7%) and 3 minor bleeding events (6.8%) could be averted with use of bivalirudin. In addition, introducing a bivalirudin-based strategy to treat a minimum cohort of 36 STEMI patients would save the hospital budget $60 807 (9%) per year. Conclusion: Using a bivalirudin-based strategy in STEMI patients undergoing PPCI is associated with favorable clinical and economic outcomes when compared with an UFH + GPI-based strategy in a US hospital setting.

Use of glycoprotein IIb/IIIa inhibitors in primary percutaneous coronary intervention: insights from the APEX-AMI trial

Controversy exists regarding the early use of glycoprotein IIb/IIIa inhibitors (GPIs) in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). The Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial provides a unique opportunity to examine early vs. late or non-use of GPIs in a large STEMI cohort treated with PCI. In the APEX-AMI trial, 3969 of 5707 patients received one of three GPIs at the operator's discretion (abciximab, eptifibatide, tirofiban). Of GPI-treated patients, the median time from symptom onset to GPI administration was 180 min (25th, 75th percentile: 130, 258); 1125 received the agent prior to arriving in the catheterization laboratory [pre-sheath; GPI to sheath insertion: 37 min (16, 66)], whereas 2844 patients were treated after arrival in the catheterization laboratory [in-lab; sheath insertion to GPI: 16 min (10, 27)]. The pre-sheath use of GPIs was associated with a significantly lower hazard of 90-day mortality [adjusted hazard ratio (HR) 0.68, 95% confidence interval (CI) 0.48-0.95, P = 0.025] and of 90-day composite of death/CHF/shock (adjusted HR 0.81, 95% CI 0.65-1.00, P = 0.054). In-hospital severe and moderate bleeding was not related to the use of GPIs. This retrospective analysis from a large patient cohort with acute STEMI undergoing PCI suggests that pharmacological pre-treatment of PCI with GPIs, particularly abciximab, was associated with significantly lower occurrence of 90-day clinical outcomes and supports the pre-procedural administration of GPIs in this clinical setting.

Optimizing primary PCI beyond “door to intervention time”—are we there yet?

To assess the effects of shortened door-to-intervention (DTI) time on appropriate clinical decisions regarding the four most critical and costly decisions during primary percutaneous coronary intervention (PCI): cath-lab activation (CLA), use of glycoprotein IIb/IIIa inhibitors (GPI), use of PCI, and deployment of drug-eluting stent (DES). STEMI PCI patients are frequently subject to decision making based on abbreviated medical encounter and limited medical information. Clinical data were prospectively collected in a STEMI registry over 19 months. Retrospective chart reviews were conducted to determine the level of appropriateness of the above-mentioned decisions. Between June 2006 and December 2007, 200 EKGs with suspected STEMI were transmitted; 88 (44%) resulted in CLA. Compared to prior year, DTI times decreased from 145.7 to 69.9 min (P=.00001). DTI was longer during nights and weekends (87.5 vs. 51.8 min, P=.001) and the initial 6 months of the registry (86.8 vs. 66.8 min, P=.07). Nineteen (21.6%) of the patients undergoing angiography did not require revascularization, 56 (63.6%) received GPIs, and 65 patients (73.8%) underwent at least one vessel PCI, and at least one DES was used in 39 patients (60% of PCI cohort). When assessed for appropriateness, CLA was appropriate in 81.8% of the time and rendered borderline or inappropriate in 5.7% and 12.5%, respectively. GPI use was appropriate in 66% of the patients but seemed borderline or inappropriate in 28.5% and 5.4%, respectively. PCI was appropriate in 90% of the lesions treated, and borderline or inappropriate in 7.1% and 2.9%, respectively. DES use was viewed appropriate in 38.4%, and borderline or inappropriate in 51% and 10.2% of the DES deployments, respectively. (1) In view of expedited care, certain information required for decision-making process is either not available or ignored during primary PCI. (2) Appropriate use of resources in primary PCI needs to be better defined. (3) Measures of extracting patients' previous medical records and imaging studies along with in-lab immediate blood work and echocardiography and establishing new "time-out" protocols for STEMI patients may improve resource utilization and patient care and outcome.