Glycoprotein IIb/IIIa Inhibitors Use Research Articles

Bivalirudin or Heparin in Patients Undergoing Invasive Management of Acute Coronary Syndromes

BackgroundContrasting evidence exists on the comparative efficacy and safety of bivalirudin and unfractionated heparin (UFH) in relation to the planned use of glycoprotein IIb/IIIa inhibitors (GPIs). ObjectivesThis study assessed the efficacy and safety of bivalirudin compared with UFH with or without GPIs in patients with acute coronary syndrome (ACS) who underwent invasive management. MethodsIn the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX) program, 7,213 patients were randomly assigned to receive either bivalirudin or UFH with or without GPIs at discretion of the operator. The 30-day coprimary outcomes were major adverse cardiovascular events (MACEs) (a composite of death, myocardial infarction, or stroke), and net adverse clinical events (NACEs) (a composite of MACEs or major bleeding). ResultsAmong 3,603 patients assigned to receive UFH, 781 (21.7%) underwent planned treatment with GPI before coronary intervention. Bailout use of GPIs was similar between the bivalirudin and UFH groups (4.5% and 5.4%) (p = 0.11). At 30 days, the 2 coprimary endpoints of MACEs and NACEs, as well as individual endpoints of mortality, myocardial infarction, stent thrombosis or stroke did not differ among the 3 groups after adjustment. Compared with the UFH and UFH+GPI groups, bivalirudin reduced bleeding, mainly the most severe bleeds, including fatal and nonaccess site−related events, as well as transfusion rates and the need for surgical access site repair. These findings were not influenced by the administered intraprocedural dose of UFH and were confirmed at multiple sensitivity analyses, including the randomly allocated access site. ConclusionsIn patients with ACS, the rates of MACEs and NACEs were not significantly lower with bivalirudin than with UFH, irrespective of planned GPI use. However, bivalirudin significantly reduced bleeding complications, mainly those not related to access site, irrespective of planned use of GPIs. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of AngioX [MATRIX]; NCT01433627)

Morphine Analgesia Pre-PPCI Is Associated with Prothrombotic State, Reduced Spontaneous Reperfusion and Greater Infarct Size.

URL: http://www.clinicaltrials.gov. Unique identifier: NCT02562690.

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.

Glycoprotein Iib/Iiia Inhibitors in Acute ST-Segment Elevation Myocardial Infarction: Evaluation of Clinical Practice and Cost/Efficacy Analysis

Associated to primary percutaneous coronary intervention (pPCI), pharmacotherapy in acute ST-Segment elevation myocardial infarction (STEMI) patients have transformed the management of the acute phase. Use of glycoprotein IIb/IIIa inhibitors (GPI) remains debatable, level of guidelines has been modified in the successive editions of guidelines. In the latest European Society of Cardiology guidelines, GPI have a IIb B level in upstream use and IIa C in bail out during pPCI procedure. In front of the varying recommendations, we analysed clinical characteristics of patients with ST-Segment elevation myocardial infarction according to the use of GPI. We evaluate complications during hospitalization, particularly bleeding events. The cost of patients’ management was also analysed. We conducted a retrospective, descriptive and monocentric study from January 2010 to December 2012 including all consecutive STEMI patients with symptoms evolving for less than 12 hours treated by pPCI. GPI were administered as recommended in patients with high thrombotic risk, low bleeding risk, with early presentation and more likely anterior location. Despite an initial more severe clinical presentation, no statistical difference among each group on in-hospital complications and duration of hospital stay was observed. Nevertheless patients treated with abciximab have a significant higher cost of overall management compared to HNF only (+30%) or other GPI (+37%). In selected clinical indications, in line with the European guidelines, GPI use appears safe, efficient and cost effective with regards to eptifibatide/tirofiban.

Combined thrombectomy and intracoronary administration of glycoprotein IIb/IIIa inhibitors improves myocardial reperfusion in patients undergoing primary percutaneous coronary intervention: a meta-analysis.

BackgroundSuboptimal myocardial reperfusion is common in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Furthermore, it results in increased infarct size and mortality rates. We performed a meta-analysis to evaluate the role of aspiration thrombectomy (AT) combined with intracoronary administration of glycoprotein IIb/IIIa inhibitors (GPI) in the improvement of myocardial reperfusion and clinical outcomes.MethodsPubMed, Embase, Web of Science, and CENTRAL databases were searched for randomized controlled trials (RCTs) investigating combined AT and intracoronary GPI treatment versus AT alone. Outcomes of interest were thrombolysis in myocardial infarction myocardial perfusion grade (TMPG), infarct size (IS) assessed by cardiac magnetic resonance imaging, left ventricular ejection fraction (LVEF), major adverse cardiac events (MACE) at short-term (≤ 1 month) and long-term (6–12 months) follow-up, and bleeding complications during the hospital stay.ResultsEight trials involving 923 patients were included. Compared with AT alone, combined AT and intracoronary GPI significantly increased TMPG 3 flow (RR: 1.15, 95% CI: 1.04 to 1.26), reduced IS [mean difference (MD): –3.46, 95% CI: –5.18 to –1.73], and improved LVEF (MD: 1.44, 95% CI: 0.54 to 2.33). Furthermore, GPI use decreased the risk of MACE at long-term follow-up (RR: 0.60, 95% CI: 0.37 to 0.98). There was no significant difference between the two groups in the incidence of minor and major bleeding complications.ConclusionsOur findings showed that compared with AT alone, combined AT and intracoronary GPI treatment resulted in improved myocardial reperfusion, better cardiac function, and MACE-free survival benefits at the long-term follow-up for patients with STEMI undergoing PPCI.

Practice Patterns and In-Hospital Outcomes Associated With Bivalirudin Use Among Patients With Non–ST-Segment–Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention in the United States

Practice patterns in anticoagulant strategies used during percutaneous coronary intervention (PCI) in the United States for patients with non-ST-segment-elevation myocardial infarction and the comparative outcomes between bivalirudin and unfractionated heparin (UFH) have not been well described. Trends in anticoagulant use were examined among 553 562 PCIs performed by 9254 operators at 1538 hospitals for non-ST-segment-elevation myocardial infarction from 2009 to 2014 within the CathPCI Registry. To compare bivalirudin with UFH, propensity score matching and instrumental variable (IV) methods with operator preference for bivalirudin as the instrument were used. To determine whether differences in outcomes were because of differences in glycoprotein IIb/IIIa inhibitor (GPI) use, a test of mediation was performed using the IV. Outcomes were in-hospital bleeding and mortality. Bivalirudin use increased from 2009 to 2013 but declined during 2014. GPI use was 50.5% during UFH PCIs and 12.0% during bivalirudin PCIs. Before GPI adjustment, bleeding reductions with bivalirudin ranged from 2.04% (IV: 95% confidence interval [CI]: 1.81%, 2.27%) to 2.29% (propensity score: 95% CI: 2.14%, 2.44%) and mortality reductions ranged from 0.16% (IV: 95% CI: 0.03%, 0.28%) to 0.25% (propensity score: 95% CI: 0.17%, 0.33%). After GPI adjustment in the IV, more than half the bleeding reduction with bivalirudin was because of the lower use of GPIs (risk difference, -0.84%; 95% CI: -1.11%, -0.57%), and no survival benefit was apparent (risk difference, -0.10%; 95% CI: -0.24%, 0.05%). Bleeding reductions with bivalirudin were largest for transfemoral PCI (GPI-adjusted risk difference, -1.11%; 95% CI: -1.43%, -0.80%) and negligible for transradial PCI (GPI-adjusted risk difference, 0.09%; 95% CI: -0.32%, 0.50%). In the largest comparative analysis of bivalirudin versus UFH for non-ST-segment-elevation myocardial infarction to date, bivalirudin was associated with lower in-hospital bleeding and mortality given current practices with respect to GPI use and access site. Bleeding differences were, in part, explained by the greater use of GPIs with UFH. Reductions in bleeding were largest among those undergoing transfemoral PCI, whereas no bleeding benefit was observed for those treated with transradial PCI.

P3697Prognostic role of non-ST resolution and glycoprotein IIbIIIa inhibitors use in STEMI patients treated with primary PCI

P3697Prognostic role of non-ST resolution and glycoprotein IIbIIIa inhibitors use in STEMI patients treated with primary PCI

Impact of anticoagulation strategy with bivalirudin or heparin on nonaccess site bleeding in percutaneous coronary interventions: A meta-analysis of randomized trials.

Transradial approach has significantly decreased the rate of access site bleeding in patients undergoing percutaneous coronary interventions (PCI), therefore potentially mitigating the benefits offered by bivalirudin in lowering major bleeding complications as compared to heparin. However, nonaccess site bleeding, that represent the majority of hemorrhagic complications, still carry negative prognostic consequences for these patients and no study has so far defined the exact impact of bivalirudin on nonaccess site bleeding, that was therefore the aim of present meta-analysis. Literature archives (Pubmed, EMBASE, Cochrane) and main scientific sessions were scanned comparing bivalirudin vs. heparin in patients undergoing PCI. Primary endpoint was the occurrence of nonaccess site bleeding within 30 days. Secondary endpoints were 30 days mortality and the occurrence of access-site bleeding. A total of nine randomized clinical trials were finally included, involving 32,587 patients, 55.8% randomized to bivalirudin. Bivalirudin significantly reduced the rate of nonaccess site bleeding (2.6 vs. 3.8%, OR [95% CI] = 0.68 [0.60-0.77], P < 0.00001, Phet = 0.10). However, the reduction of hemorrhagic events was more pronounced when bivalirudin was compared to heparin plus glycoprotein IIbIIIa inhibitors than when it was compared to heparin alone (r = -0.01 (-0.02; -0.001), P = 0.02). Similar results were observed for access-site bleeding (OR [95% CI] = 0.67 [0.57-0.79], P < 0.000001, Phet = 0.10), with a significant role of glycoprotein IIbIIIa inhibitors use (r = -0.02 (-0.04; -0.004), P = 0.017). Moreover, the observed benefits in hemorrhagic complications did not translate into mortality benefits (OR [95% CI] = 0.89 [0.76-1.05], P = 0.18; Phet = 0.12; r = 0.21 (-1.12; 1.53), P = 0.76). The present meta-analysis shows that bivalirudin can provide a significant reduction of both access and nonaccess site bleeding in patients undergoing PCI. However, these hemorrhagic benefits did not impact on survival, and moreover, were significantly conditioned by the association of heparin with potent antithrombotic strategies, such as glycoprotein IIbIIIa inhibitors, rather than by heparin or bivalirudin alone. Therefore, we could not provide any clinical evidence for the routine use of bivalirudin as preferred anticoagulation strategy for PCI. © 2017 Wiley Periodicals, Inc.

Cangrelor With and Without Glycoprotein IIb/IIIa Inhibitors in Patients Undergoing Percutaneous Coronary Intervention

BackgroundCangrelor, an intravenous, reversible P2Y12 antagonist, is approved for use in patients undergoing percutaneous coronary intervention (PCI). ObjectivesThis study sought to evaluate the efficacy and safety of cangrelor compared with clopidogrel in subgroups that did and did not receive glycoprotein IIb/IIIa inhibitors (GPIs). MethodsThis pooled, patient-level analysis of the 3 CHAMPION (Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trials analyzed all randomized patients who underwent PCI and received the study drug (n = 24,902). Only bailout/rescue GPI use was permitted, except in CHAMPION PCI, in which routine or bailout/rescue GPI use was at the site investigator’s discretion. The primary efficacy endpoint was the composite of all-cause mortality, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 h after randomization. ResultsOverall, 3,173 patients (12.7%) received a GPI, most commonly eptifibatide (69.4%). Despite variation in indications for GPIs, baseline characteristics were well balanced between the cangrelor and clopidogrel arms in subsets receiving and not receiving GPIs. Rates of the primary composite endpoint were lower with cangrelor compared with clopidogrel in patients who did (4.9% vs. 6.5%; odds ratio [OR]: 0.74; 95% confidence interval [CI]: 0.55 to 1.01) or did not receive a GPI (3.6% vs. 4.4%; OR: 0.82; 95% CI: 0.72 to 0.94; Pint = 0.55). Cangrelor did not increase the primary safety endpoint, GUSTO-defined severe/life-threatening bleeding, in patients who did (0.4% vs. 0.5%; OR: 0.71; 95% CI: 0.25 to 1.99) or did not receive GPIs (0.2% vs. 0.1%; OR: 1.56; 95% CI: 0.80 to 3.04; Pint = 0.21). GPI use was associated with increased risk of bleeding in both treatment arms. ConclusionsCangrelor’s efficacy in reducing ischemic complications in patients undergoing PCI was maintained irrespective of GPI administration. GPI use was associated with substantially higher bleeding rates, regardless of the randomization to cangrelor or clopidogrel. (A Clinical Trial to Demonstrate the Efficacy of Cangrelor [PCI]: NCT00305162; Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition [PLATFORM]: NCT00385138; A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI] [CHAMPION PHOENIX] [CHAMPION]: NCT01156571)

Pre-Hospital Ambulance Notification for ST Elevation Myocardial Infarction (STEMI) Leads to Rapid Reperfusion But No Effect on Early Mortality: Insights from the Melbourne Interventional Group (MIG) Registry

Background: Guidelines for acute coronary syndrome management advocate a 12-lead electrocardiogram should be taken en route and transmitted to prenotify the receiving medical facility. The aim is to obtain a door-to-balloon time (DTBT) <90mins. We sought to analyse the benefits of prenotification. Method: Excluding cardiac arrest, consecutive patients undergoing primary PCI for STEMI between 2011-2016 from the MIG registry were included with analysis separated into prenotified and non-prenotified groups. Results: 1134 prenotified (38.6%) and 1806 non-prenotified (61.4%) cases were compared. The prenotified group has a higher proportion of patients >75yo (29.0% vs 22.8%, p = 0.01) and have an eGFR<60 mL/min/1.73m2 (28.2% vs 22.7%, p<0.01), but a similar cardiogenic shock rate (6.7% vs 5.2%, p = 0.12). The prenotified group has a higher thrombus aspiration use (30.2% vs 22.4%, p < 0.001), glycoprotein IIbIIIa inhibitor use (66.6% vs 53.4%, p < 0.001), RCA intervention (47.1% vs 36.5%, p < 0.001) and bare metal stent use (40.5%vs36.0%, p < 0.05) with similar procedural success (95.7% vs 95.2%, p = 0.54). Prenotification leads to a 36 min shorter DTBT (52mins vs 88mins, p < 0.001). Prenotification increases total DTBT < 90mins (88.9% vs 51.3%, p < 0.001), increases in hours DTBT<90mins (93.3% vs 61.6%, p < 0.001) and after hours DTBT < 90mins (85.6 vs 46.0%, p < 0.001). Prenotification has a higher in-hospital (4.6% vs 2.9%, p < 0.05) and 30-day mortality (5.1% vs 3.6%, p < 0.05). Prenotification is not an independent predictor for 30-day mortality (HR 1.37, 95% CI 0.91-2.07). Conclusion: Although prenotification dramatically improves DTBTs (especially after hours) and reduces total ischaemic time, early mortality is not lower. The effect on long term mortality after STEMI is eagerly awaited.

Antithrombotic therapy before, during and after emergency angioplasty for ST elevation myocardial infarction.

The first three hours after symptom onset hold the maximum potential for myocardial reperfusion and salvage in ST-elevation myocardial infarction (STEMI) patients. During this period timely primary percutaneous coronary intervention (PPCI) or, when PPCI is not promptly feasible, pre-hospital administration of fibrinolyis or a glycoprotein IIb/IIIa-inhibitor (GPI) have been shown to restore coronary patency and reperfusion and even result in myocardial infarction (MI) abortion. On the other hand, oral antiplatelet therapy may not yet guarantee sufficient platelet inhibition. Patients presenting after this golden time have less, if any, benefit from an aggressive antithrombotic treatment prior to PPCI. Antithrombotic treatment during primary angioplasty should be tailored on the basis of the coronary thrombotic burden, vascular approach and the patient's risk of bleeding complications. A GPI-based approach may be favourable in patients presenting early with large MI and high thrombus burden, whereas a bivalirudin-based approach without GPI may be preferred in patients with higher bleeding risk. There are no data to support the use of GPI in bailout conditions. The powerful oral P2Y12 inhibitors, prasugrel and ticagrelor, have been clearly shown to prevent stent thrombosis and recurrent ischaemic events after emergency percutaneous coronary intervention in STEMI patients. Open issues remaining are the treatment of patients with high bleeding risk, such as the elderly and those requiring anticoagulation, as well as the duration of dual antiplatelet therapy after STEMI.

Safety of glycoprotein IIb/IIIa inhibitors in patients under therapeutic hypothermia admitted for an acute coronary syndrome

BackgroundMild therapeutic hypothermia (MTH) is associated with an increased risk of both thrombotic and bleeding events. Although little is known about the use of Glycoprotein IIb-IIIa inhibitors (GPi) in this setting, the early action and the intravenous administration of these agents in patients who cannot swallow might potentially translate into clinical benefits in patients with acute coronary syndromes (ACS). AimsTo assess the incidence of bleeding/thrombotic events in patients with ACS under MTH after an Out-of-hospital cardiac arrest (OHCA) who received GPi or not. Methods and ResultsFrom January 2010 to September 2015, 110 patients were treated with MTH after an OHCA. Among them, 88 (80%) had an ACS and 71 patients (80.6%) underwent percutaneous coronary intervention (PCI). In 17 (24%) GPi were administered in the cath-lab. During hospitalization, 11.7% in the GPi and 9.25%in the non GPi group presented thrombotic events (stent thrombosis, deep vein thrombosis, pulmonary embolism) without significant differences between groups (p= 0.762). The incidence of any bleeding (64.7% vs. 14.8%; p<0.0001), and major bleeding (41.1% vs. 3.7; p<0.0001) was significantly higher in patients receiving GPi. Finally, in-hospital mortality did not differ between groups (24% vs. 35, 2%; p=0.385). ConclusionsIn this study, the use of GPi in patients with ACS undergoing PCI under MTH was associated with an increased bleeding risk without reduction of thrombotic events. According to these results, the use of GPi should be carefully considered in this setting.

Trends in primary angioplasty in Portugal from 2002 to 2013 according to the Portuguese National Registry of Interventional Cardiology

Introduction and ObjectivesThe aim of the present paper was to report trends in coronary angioplasty for the treatment of ST-elevation myocardial infarction (STEMI) in Portugal. MethodsProspective multicenter data from the Portuguese National Registry of Interventional Cardiology (RNCI) and official data from the Directorate-General for Health (DGS) were studied to analyze percutaneous coronary intervention (PCI) procedures for STEMI from 2002 to 2013. ResultsIn 2013, 3524 primary percutaneous coronary intervention (p-PCI) procedures were performed (25% of all procedures), an increase of 315% in comparison to 2002 (16% of all interventions). Between 2002 and 2013 the rate increased from 106 to 338 p-PCIs per million population per year. Rescue angioplasty decreased from 70.7% in 2002 to 2% in 2013. During this period, the use of drug-eluting stents grew from 9.9% to 69.5%. After 2008, the use of aspiration thrombectomy increased, reaching 46.7% in 2013. Glycoprotein IIb-IIIa inhibitor use decreased from 73.2% in 2002 to 23.6% in the last year of the study. Use of a radial approach increased steadily from 8.3% in 2008 to 54.6% in 2013. ConclusionDuring the reporting period there was a three-fold increase in primary angioplasty rates per million population. Rescue angioplasty has been overtaken by p-PCI as the predominant procedure since 2006. New trends in the treatment of STEMI were observed, notably the use of drug-eluting stents and radial access as the predominant approach.

Why we need intravenous antiplatelet agents.

Oral ADP-receptor antagonists combined with aspirin are the standard for dual antiplatelet therapy (DAPT) during percutaneous coronary intervention (PCI). However, the oral route of administration of ADP-receptor antagonists leaves them vulnerable to unpredictable and often inadequate platelet inhibition at the time of PCI, while their prolonged effects often lead to the decision not to load them prior to PCI. Intravenous antiplatelet agents, including glycoprotein IIb/IIIa inhibitors (GPI) and cangrelor, a reversible P2Y12 inhibitor, address these shortcomings. In June 2015, the US FDA approved cangrelor for the prevention of thrombotic events associated with coronary stenting. This review examines the current state of peri-PCI DAPT and demonstrates that the selective use of GPIs and intravenous ADP-antagonist agents reduces the risk of periprocedural thrombosis.

Impact of glycoprotein IIb/IIIa inhibitors on the efficacy and safety of ticagrelor compared with clopidogrel in patients with acute coronary syndromes: Analysis from the Platelet Inhibition and Patient Outcomes (PLATO) Trial

Ticagrelor reduced cardiovascular events compared with clopidogrel in PLATO without increasing overall major bleeding. We evaluated whether the use of glycoprotein IIb/IIIa inhibitor (GPI) impacts the relative efficacy and safety of ticagrelor compared with clopidogrel. PLATO randomized 18,624 subjects with acute coronary syndrome to ticagrelor versus clopidogrel. The primary efficacy end point was cardiovascular death/myocardial infarction/stroke, and the primary safety end point was major bleeding. The use of GPI was at the physician's discretion and open-label. We evaluated outcomes at 30 days stratified by GPI use in the subgroup of 9,983 patients who underwent percutaneous coronary intervention (PCI) within 72 hours. A total of 4,020 (40%) received a GPI. Those receiving a GPI were more likely to be younger, be male, and undergo multivessel PCI. There was no interaction between treatment and GPI use for the primary efficacy and safety end points. Patients treated without GPI had a lower rate of definite stent thrombosis and higher rate of minor/major bleeding with ticagrelor compared with clopidogrel (P < .05), whereas there was no such difference with GPI (P interaction < .05). In patients with acute coronary syndrome undergoing early PCI, the efficacy and safety of ticagrelor as compared with clopidogrel were not modified by GPI use according to the primary efficacy and safety end point of the trial, although there were indications of greater benefit on definite stent thrombosis and more major or minor bleeding with ticagrelor in patients without (vs with) GPI treatment.

The Current Role of Glycoprotein IIb/ IIIa Inhibitors in Percutaneous Coronary Intervention*

The central role of platelets in acute coronary syndromes (ACS) and percutaneous coronary interventions (PCI) is well appreciated. The various platelet activation mechanisms finally lead to the expression and activation of surface glycoprotein IIb/IIIa receptors that mediate platelet aggregation and thrombus formation. Glycoprotein IIb/IIIa inhibitors (GPIs) are the most potent antiplatelent agents and their role in ACS treatment and PCI has been dominant in the recent past. The advent of stents and thienopyridines minimized ischemic complications and in parallel the role of GPIs in low risk PCI. Despite being effective in decreasing PCI-related ischemic complications, the major drawback of GPI use is a relative increase of hemorrhagic complications that can unfavorably affect prognosis. The availability of bivalirudin, which is regarded as an equally effective but safer antithrombotic agent when compared to the combination of heparin and GPIs, despite an ongoing controversy, has also led to a decrease of GPI use in PCI for ACS. Finally the advent of novel potent antiplatelet agents (prasugrel, ticagrelor and soon cangrelor) further contained GPI use in patients with ischemic – thrombotic risk that clearly exceeds bleeding risk and mainly for bail-out in case of a thrombotic event during PCI. A concise overview of accumulated data regarding optimal use of GPIs as determined by large clinical trials and recent guidelines is herein attempted.

Impact of Glycoprotein IIb/IIIa Inhibitors Use on Outcomes After Lower Extremity Endovascular Interventions From Nationwide Inpatient Sample (2006-2011).

The aim of our study was to study the impact of glycoprotein IIb/IIIa inhibitors (GPI) on in-hospital outcomes. There is paucity of data regarding the impact of GPI on the outcomes following peripheral endovascular interventions. The study cohort was derived from Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) database between the years 2006 and 2011. Peripheral endovascular interventions and GPI utilization were identified using appropriate ICD-9 Diagnostic and procedural codes. Two-level hierarchical multivariate mixed models were created. The study outcomes were: primary (in-hospital mortality and amputation studied separately) and secondary (composite of in-hospital mortality and postprocedural complications). Hospitalization costs were also assessed. GPI utilization (OR, 95% CI, P-value) was independently predictive of lower amputation rates (0.36, 0.27-0.49, <0.001). There was no significant difference in terms of in-hospital mortality (0.59, 0.31-1.14, P 0.117), although GPI use predicted worse secondary outcomes (1.23, 1.03-1.47, 0.023). Following propensity matching, the amputation rate was lower (3.2% vs. 8%, P < 0.001), while hospitalization costs were higher in the cohort that received GPI ($21,091 ± 404 vs. 19,407 ± 133, P < 0.001). Multivariate analysis revealed GPI use in peripheral endovascular interventions to be suggestive of an increase in composite end-point of in-hospital mortality and postprocedural complications, no impact on in-hospital mortality alone, significantly lower rate of amputation, and increase in hospitalization costs. © 2016 Wiley Periodicals, Inc.

An updated comprehensive meta-analysis of bivalirudin vs heparin use in primary percutaneous coronary intervention

Despite several randomized controlled trials and meta-analyses, the ideal anticoagulant for patients undergoing primary percutaneous coronary intervention (PCI) remains controversial. We performed an updated meta-analysis including recently reported randomized clinical trials that compare bivalirudin and heparin with or without provisional administration of a glycoprotein IIb/IIIa inhibitor (GPI) for primary PCI. Scientific databases and Web sites were searched for randomized clinical trials. Data from 6 trials involving 14,095 patients were included. The pooled risk ratios (RRs) were calculated using random-effects models. Moderator analyses examined the impact of routine use of GPI, radial access, and P2Y12 inhibitors on safety outcomes. At 30 days, patients receiving bivalirudin had rates of major adverse cardiac events similar to those receiving heparin with or without provisional GPI (RR 1.02, 95% CI 0.87-1.19, P = .800), myocardial infarction (RR 1.41, 95% CI 0.94-2.11, P = .089), target vessel revascularization (RR 1.37, 95% CI 0.91-2.04, P = .122), and net adverse clinical events (RR 0.81, 95% CI 0.64-1.01, P = .069). However, bivalirudin use decreased the risk of all-cause mortality (RR 0.81, 95% CI 0.67-0.99, P = .041) and cardiac mortality (RR 0.68, 95% CI 0.51-0.91, P = .009) at 30 days, There were higher rates of acute stent thrombosis (RR 3.31, 95% CI 1.79-6.10, P < .001) in patients receiving bivalirudin. Bivalirudin use also decreased the risk of major bleeding at 30 days by 37% (RR 0.63, 95% CI 0.44-0.90, P = .012), but bleeding risk varied depending on routine GPI use with heparin (RR 0.44, 95% CI 0.23-0.81, P = .009) vs bailout (RR 0.73, 95% CI 0.42-1.25, P = .252), predominantly radial access (RR 0.54, 95% CI 0.25-1.15, P = .114) vs non-radial access (RR 0.60, 95% CI 0.36-0.99, P = .049), and second-generation P2Y12 inhibitor use with bivalirudin (RR 0.70, 95% CI 0.40-1.24, P = .226) vs clopidogrel use (RR 0.39, 95% CI 0.18-0.85, P = .018). In primary PCI, relative to heparin, bivalirudin reduces the risk for all-cause mortality, cardiac mortality, and major bleeding but yields similar rates of major adverse cardiac event and net adverse clinical event at 30 days. However, the benefit of a reduction in bleeding with bivalirudin appears to be modulated by the concurrent administration of second-generation P2Y12 inhibitors with bivalirudin, using radial access, and avoiding routine GPI use with heparin.

Impact of Glycoprotein IIb/IIIa Inhibition inContemporary Percutaneous CoronaryIntervention for Acute CoronarySyndromes: Insights From the National Cardiovascular Data Registry.

This study investigates the effects of glycoprotein IIb/IIIa inhibitors (GPIs) on outcomes after percutaneous coronary intervention (PCI). Ischemic complications are reduced after PCI when a GPI is added to heparin. However, there are limited data on the safety and efficacy in contemporary PCI. We used the National Cardiovascular Data Registry CathPCI Registry data to assess the association between GPI use and PCI outcomes for acute coronary syndrome between July 2009 and September 2011. The primary outcome was all-cause in-hospital mortality. The secondary outcome was major bleeding. To adjust for potential bias, we used multivariable logistic regression, propensity-matched (PM) analysis, and instrumental variable analysis (IVA). There were 970,865 patients included; 326,283 (33.6%) received a GPI. Unadjusted mortality and major bleeding were more common with a GPI (2.4% vs. 1.4% and 3.7% vs. 1.5%, respectively; p< 0.001 for both). In contrast, GPI use was associated with lower mortality on adjusted analyses; relative risks range from 0.72 (95% confidence interval [CI]: 0.50 to 0.97) with IVA to 0.90 (95% CI: 0.86 to 0.95) with PM. The association of GPI use with bleeding remained in adjusted analyses (multivariable relative risk: 1.93, 95% CI: 1.83 to 2.04; PM relative risk: 1.83, 95% CI: 1.74 to 1.92; and IVA relative risk: 1.53, 95% CI: 1.27 to 2.13). Subgroup analysis revealed enhanced risk reduction with ST-segment elevation myocardial infarction, high predicted mortality, and heparin-based anticoagulation. In unselected acute coronary syndrome patients undergoing PCI, GPI use was associated with reduced in-hospital mortality and increased bleeding. In the modern era of PCI, there may still be a role for the judicious use of GPIs.

Platelet GP IIb-IIIa Receptor Antagonists in Primary Angioplasty: Back to the Future.

Coronary artery disease and acute myocardial infarction still represent the leading cause of mortality in developed countries. Therefore, great efforts have been made in the last decades to improve reperfusion strategies and adjunctive antithrombotic therapies. In fact, despite optimal epicardial recanalisation, a large proportion of patients still experience impaired reperfusion and in-stent thrombosis. The adjunctive use of glycoprotein (GP) IIb-IIIa inhibitors may certainly contribute in the reduction of such complications, especially when administered in the early phase of infarction. In fact, in this phase a larger platelet composition of the thrombus and the presence of a larger amount of viable myocardium, as compared to a delayed phase, may increase the benefits from this therapy and counterbalance the potential higher risk of bleeding. A large body of evidence has been accumulated on the benefits from GP IIb-IIIa inhibitors in terms of prevention of stent thrombosis, and benefits in mortality, especially among high-risk patients and as upstream strategy. Therefore, based on current available data, GP IIb-IIIa inhibitors can be recommended as early as possible (upstream strategy) among high-risk patients, such as those with advanced Killip class or anterior myocardial infarction (MI), and those presenting within the first three hours. Even though it is not universally accepted, in our opinion this strategy should be implemented in a pre-hospital setting (in ambulance) or at first hospital admission (Emergency Room or Coronary Care Unit, irrespective of whether they are in the spoke or hub hospitals). Peri-procedural intracoronary administration of GP IIb-IIIa inhibitors has not provided additional benefits as compared to intravenous administration and therefore cannot be recommended. Even though the vast majority of trials have been conducted with abciximab, several meta-analyses comparing small molecules (mainly high-dose tirofiban rather than eptifibatide) versus abciximab showed similar angiographic and clinical results between the molecules. Several recent investigations and meta-analyses have documented the higher risk of stent thrombosis associated with bivalirudin as compared to unfractionated heparin (UFH). Being that these results are independent from the use of GP IIb-IIIa inhibitors, UFH should still remain the anticoagulation therapy of choice in ST-segment elevation myocardial infarction (STEMI) patients. Minimisation of bleeding complications by extensive use of the radial approach, in the setting of STEMI, may further contribute to the adoption of a more aggressive antithrombotic and antiplatelet therapy incorporating the use of GP IIb-IIIa inhibitors. The establishment of dedicated networks for STEMI, and the large STEMI campaign, will certainly contribute to increase the proportion of patients presenting at first medical contact within the early phase (3h) of infarction and therefore highly suitable for a more aggressive pharmacoinvasive approach with upstream administration of GP IIb-IIIa inhibitors. In fact, although the current therapeutic targets of increased rates of timely reperfusion, mainly by primary percutaneous coronary intervention (PCI), has been achieved, a deep look into the future in the fight against MI will certainly put aborting infarction as the major desirable target to be achieved.