Glycoprotein IIb/IIIa Inhibitors Research Articles

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.

Early Stent Thrombosis and Mortality After Primary Percutaneous Coronary Intervention in ST-Segment-Elevation Myocardial Infarction: A Patient-Level Analysis of 2 Randomized Trials.

Early stent thrombosis (ST) within 30 days after primary percutaneous coronary intervention in ST-segment-elevation myocardial infarction is a serious event. We sought to determine the predictors of and risk of mortality after early ST according to procedural antithrombotic therapy. In a patient-level pooled analysis from the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) and European Ambulance Acute Coronary Syndrome Angiography (EUROMAX) trials, we examined 30-day outcomes in 4935 patients undergoing primary percutaneous coronary intervention with stent implantation at 188 international sites, randomized to either bivalirudin or heparin±a glycoprotein IIb/IIIa inhibitor (GPI). Early ST occurred in 100 patients (2.0%), 20 of whom (20.0%) died. Bivalirudin was associated with higher rates of early ST compared with heparin±GPI (2.5% versus 1.6%, P=0.04), because of more acute (≤24 h) ST (1.5% versus 0.2%, P<0.0001), with the risk limited to the first 4 hours after percutaneous coronary intervention. The rates of subacute (1-30 days) ST were similar with bivalirudin and heparin±GPI (1.0% versus 1.4%, P=0.24). Among patients with early ST, mortality within 30 days occurred in 4 of 60 (6.7%) bivalirudin-treated patients compared with 16 of 40 (40.0%) heparin±GPI-treated patients (adjusted hazard ratio, 0.12; 95% CI, 0.04-0.39; P=0.0004 and adjusted hazard ratio, 0.122; 95% CI, 0.04-0.39; P=0. 0004). Thus, 30-day mortality attributable to early ST occurred in 4 of 2479 (0.2%) bivalirudin-treated patients versus 16 of 2456 (0.7%) heparin±GPI-treated patients (P=0.007). In the present large-scale pooled analysis from 2 multicenter randomized trials, early ST was more frequent in patients treated with bivalirudin compared with heparin±GPI because of increased ST within 4 hours after primary percutaneous coronary intervention. However, the mortality attributable to early ST was significantly lower after bivalirudin than after heparin±GPI. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00433966 (HORIZONS-AMI) and NCT01087723 (EUROMAX).

Safety and Efficacy of Bivalirudin in Patients With Diabetes Mellitus Undergoing Percutaneous Coronary Intervention: From the REPLACE-2, ACUITY and HORIZONS-AMI Trials

Optimal antithrombotic pharmacotherapy in patients affected by diabetes mellitus (DM) undergoing percutaneous coronary intervention is unclear. We sought to evaluate the safety and efficacy of bivalirudin compared with heparin plus a glycoprotein IIb/IIIa inhibitor (GPI) in patients with DM undergoing percutaneous coronary intervention. We pooled patient-level data from the Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events-2, Acute Catheterization and Urgent Intervention Triage strategy, and Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction trials. The primary efficacy end point was the incidence of major adverse cardiac events, defined as the composite of death, myocardial infarction, or unplanned revascularization at 30days. The primary safety end point was the incidence of 30-day non-coronary artery bypass graft-related major bleeding. All-cause mortality was reported at 30days and 1year. Of the 14,737 patients included in the pooled database, 3,641 (24.7%) had DM. Patients with DM had higher rates of 30-day major bleeding and 30-day and 1-year all-cause mortality. There were no differences in 30-day major adverse cardiac events between bivalirudin versus heparin plus GPI in patients with DM (6.9% vs 7.8%; relative risk [RR] 0.89, 95% CI 0.71 to 1.12) or without DM (7.5% vs 6.7%; RR 1.11, 95% CI 0.97 to 1.27; pinteraction= 0.10). Bivalirudin treatment was associated with reduced risk of major bleeding in similar magnitude in patients with DM (4.3% vs 6.6% RR 0.68, 95% CI 0.51 to 0.89) or without DM (3.2% vs 6.1%; RR 0.51, 95% CI 0.43 to 0.61; pinteraction= 0.15). The hemorrhagic benefit of bivalirudin was noted for both access site- and non-access site-related bleeding. Overall, bivalirudin treatment was associated with a significant 1-year mortality benefit (2.7% vs 3.3%; RR 0.82, 95% CI 0.68 to 0.98; p= 0.03), which was consistent between patients with or without DM (pinteraction= 0.30). In conclusion, compared with heparin plus GPI, bivalirudin was associated with similar 30-day antithrombotic efficacy and better 30-day freedom from bleeding and 1-year mortality, irrespective of diabetic status.

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.

CRT-200.83 Comparison of High-Dose Bolus Tirofiban With Other Anticoagulation Strategies for Percutaneous Coronary Intervention: A Network Meta-Analysis of Randomized Controlled Trials

Numerous randomized controlled trials (RCTs) have been conducted comparing different anticoagulation strategies for percutaneous coronary intervention (PCI) but comparison between different glycoprotein IIb/IIIa inhibitors (GPI) is limited. Thus, we performed a Bayesian network meta-analysis to

Trends in use of anti-thrombotic agents and outcomes in patients with non-ST-segment elevation myocardial infarction (NSTEMI) managed with an invasive strategy

ObjectiveTo analyze trends in utilization of anti-thrombotic agents (ATA) and in-hospital clinical outcomes in non-ST-elevation myocardial infarction (NSTEMI) patients managed with an invasive strategy from 2007 to 2010. Methods & resultsUsing ACTION Registry®-GWTG™ data, we analyzed trends in use of ATA and in-hospital clinical outcomes among 64,199 NSTEMI patients managed invasively between 2007 and 2010. ATA included unfractionated heparin (UFH), low molecular weight heparin (LMWH), glycoprotein IIb/IIIa inhibitors (GPI) and bivalirudin. Although the proportion of NSTEMI patients treated with PCI within 48h of hospital arrival was similar in 2007 and 2010, percentage use of bivalirudin (13.4–27.3%; p<0.01) and UFH increased (60.0–67.5%, p<0.01), and that of GPI (62.3–41.0%; p<0.01) and LMWH (41.5–36.8%; p<0.01) declined. Excess dosing of UFH (75.9–59.3%, p<0.01), LMWH (9.6–5.2%; p<0.01) and GPI (8.9–5.9%, p<0.01) was also significantly lower in 2010 compared with 2007. Though in-hospital mortality rates were similar in 2007 and 2010 (2.3–1.9%, p=0.08), the rates of in-hospital major bleeding (8.7–6.6%, p<0.01) and non-CABG related RBC transfusion (6.3–4.6%, p<0.01) were significantly lower in 2010 compared with 2007. ConclusionCompared with 2007, patients with NSTEMI, who were managed invasively in 2010 received GPI and LMWH less often and bivalirudin and UFH more frequently. There were sizeable reductions in the rates of excess dosing of UFH (though still occurred in 67% of patients), GPI and LMWH. In-hospital major bleeding complications and post-procedural RBC transfusion were lower in 2010 compared with 2007.

Impact of Bleeding and Bivalirudin Therapy on Mortality Risk in Women Undergoing Percutaneous Coronary Intervention (from the REPLACE-2, ACUITY, and HORIZONS-AMI Trials)

Women have higher bleeding complication and mortality rates after percutaneous coronary interventions (PCI). The contribution of female gender to bleeding and mortality is poorly understood. We evaluated the effect of gender and bleeding on outcomes of patients treated with bivalirudin during PCI by performing a patient-level pooled analysis of 3 randomized controlled trials (the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events, Acute Catheterization and Urgent Intervention Triage strategY, and Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) comparing bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitor (GPI) treatment in patients undergoing PCI. Of 14,784 patients, 7,413 patients received bivalirudin (1,870 women) and 7,371 patients received heparin + GPI (1,910 women). Women had significantly higher 30-day non-coronary artery bypass grafting (CABG)-related major bleeding rates (7.6% vs 3.8%, p <0.0001). After multivariate adjustment, female gender increased the hazard of major bleeding by 80% (hazard ratio 1.80, 95% confidence interval 1.52 to 2.11, p <0.001). Furthermore, women had a higher 1-year mortality rate (3.7% vs 2.7%, p = 0.002) than men; 30-day major bleeding was the strongest independent predictor of 1-year mortality in women (hazard ratio 2.48, 95% confidence interval 1.57 to 3.91, p = 0.001). Bivalirudin therapy in women reduced 30-day non-CABG-related major bleeding (5.6% vs 9.7%, p <0.0001) and 1-year mortality (2.9% vs 4.4%, p = 0.02) compared to standard therapy. In conclusion, in this cohort of patients treated for acute coronary syndrome and ST-segment elevation myocardial infarction, women have a near 2-fold increase in bleeding complications compared to men after PCI. Bleeding complications rather than gender is the strongest independent predictor of 1-year mortality in patients undergoing PCI. Furthermore, we observed a more pronounced clinical benefit in women treated with bivalirudin including a 44% reduction in major bleeding and a significant reduction in mortality rates at 1 year.

Ischaemic heart disease – a selected review of recent developments

The purpose of this review is to highlight important and interesting advances in the field of ischaemic heart disease that have occurred over the last 18 months. It is focused on research that is likely to lead to changes in clinical practice. There is new evidence on appropriate pharmacotherapy during angioplasty in both stable and unstable patients. The use of pressure wire assessment has been shown to improve patient outcome. The management of patients with ST elevation myocardial infarction (STEMI) is likely to change with a reduction in the use of manual thrombectomy and an increase in the treatment of nonculprit disease. The optimal duration of dual antiplatelet therapy in percutaneous coronary intervention remains an intensely debated topic with contradictory results from major trials. Pressure wire guided coronary intervention reduces the need for urgent revascularization. The use of fractional flow reserve computed tomography has the potential to revolutionize functional testing. The treatment of patients presenting with ST elevation myocardial infarction is likely to change dramatically. Heparin with bailout glycoprotein IIbIIIa-inhibitor (GPIIbIIIa-I) appears superior to bivalirudin alone, although there is no longer a role for routine manual thrombectomy. Multivessel PCI to establish complete revascularization may become the gold standard in patients presenting with STEMI, although larger trials are needed. Novel therapies are being devised for the treatment of patients with intractable angina, but further work is required in this area.

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.

GW26-e1352 Bivalirudin Versus Heparin Plus Glycoprotein IIb/IIIa Inhibitors in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: a Meta-Analysis of Randomized Controlled Trials

This study sought to examine the 30-day safety and efficacy of bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitors (GPI) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). We included data from 12 randomized controlled trials (RCT)

Bivalirudin versus unfractionated heparin: a meta-analysis of patients receiving percutaneous coronary intervention for acute coronary syndromes

ObjectiveAcute coronary syndrome (ACS) encompasses ST segment elevation myocardial infarction (STEMI), with generally high thrombus burden and non-ST segment elevation ACS (NSTE-ACS), with lower thrombus burden. In the setting of...

Long-term results of the randomized comparison of everolimus-eluting stents and sirolimus-eluting stent in patients with ST elevation myocardial infarction (RACES-MI trial)

BackgroundSeveral concerns have emerged about the higher risk of very late stent thrombosis (ST) with first generation drug-eluting stent (DES), especially in ST-segment elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI). New generation DES have demonstrated reduction in ST at mid-term follow-up, however no data are available on long-term follow-up. Therefore, the aim of this study was to report long-term results of the RACES-MI trial conducted to compare Everolimus-Eluting Stent (EES) vs Sirolimus-Eluting Stent (SES) in patients undergoing primary PCI. MethodsThe RACES-MI trial enrolled consecutive STEMI patients admitted within 12h of symptom onset, undergoing primary PCI with stent implantation at a tertiary center with 24-hour primary PCI capability, who were randomly assigned to SES or EES. Primary endpoint of this analysis is major adverse cardiac events (MACE) at long-term follow-up. Secondary endpoints are 1) death; 2) reinfarction; 3) definite or probable ST; 4) target-vessel revascularization (TVR) at long-term follow-up. ResultsFrom April 2007 to May 2009 500 patients with STEMI were randomized to EES (n=250) or SES (n=250). No difference was observed between the groups either in baseline clinical characteristics, in the number of implanted stent or total stent length per patient. However, a larger reference diameter was observed with SES (3.35±0.51mm vs 3.25±0.51mm, p=0.001), whereas patients randomized to EES received Gp IIb–IIIa inhibitors more often (54.4% vs 42.4%, p=0.006). At long-term follow-up (2132±528days), EES was associated with a significant reduction in MACE (23.8 vs 34.1%, adjusted p=0.028), ST (2.5% vs 7.7%, adjusted p=0.009), without any difference in death (8.7% vs 11.4%, adjusted p=0.47), reMI (9.3% vs 13.1%; adjusted p=0.18) and TVR (8.6% vs 12.3%, adjusted p=0.31). ConclusionsThis study shows that among STEMI patients undergoing primary PCI EES, as compared to SES, is associated with significant reduction in MACE and ST at long-term follow-up.

ST-segment resolution with bivalirudin versus heparin and routine glycoprotein IIb/IIIa inhibitors started in the ambulance in ST-segment elevation myocardial infarction patients transported for primary percutaneous coronary intervention: The EUROMAX ST-segment resolution substudy.

Myocardial reperfusion after primary percutaneous coronary intervention (PCI) can be assessed by the extent of post-procedural ST-segment resolution. The European Ambulance Acute Coronary Syndrome Angiography (EUROMAX) trial compared pre-hospital bivalirudin and pre-hospital heparin or enoxaparin with or without GPIIb/IIIa inhibitors (GPIs) in primary PCI. This nested substudy was performed in centres routinely using pre-hospital GPI in order to compare the impact of randomized treatments on ST-resolution after primary PCI. Residual cumulative ST-segment deviation on the single one hour post-procedure electrocardiogram (ECG) was assessed by an independent core laboratory and was the primary endpoint. It was calculated that 762 evaluable patients were needed to show non-inferiority (85% power, alpha 2.5%) between randomized treatments. A total of 871 participated with electrocardiographic data available in 824 patients (95%). Residual ST-segment deviation one hour after PCI was 3.8±4.9 mm versus 3.9±5.2 mm for bivalirudin and heparin+GPI, respectively ( p=0.0019 for non-inferiority). Overall, there were no differences between randomized treatments in any measures of ST-segment resolution either before or after the index procedure. Pre-hospital treatment with bivalirudin is non-inferior to pre-hospital heparin + GPI with regard to residual ST-segment deviation or ST-segment resolution, reflecting comparable myocardial reperfusion with the two strategies.

Utilization of anticoagulants and outcomes in STEMI patients undergoing PPCI in the US hospitals: Bivalirudin, heparin plus GPI or heparin alone?

Objective. Despite major trials showing the opposite, one of three small randomized trials conducted outside the US has raised questions about whether heparin alone is a viable antithrombotic strategy for primary percutaneous coronary interventions (PPCI). We determined the frequency and in-hospital outcomes of anticoagulation strategies in patients undergoing PPCI. Methods. We analyzed records from 2008 through 2013 in the Premier Research Database of patients hospitalized with ST-segment elevation myocardial infarction (STEMI) undergoing PPCI. Patients were categorized into one of four anticoagulation strategies: bivalirudin alone, bivalirudin plus glycoprotein IIb/IIIa inhibitors (GPI), unfractionated or low-molecular-weight heparin alone or heparin plus GPI. In-hospital clinical outcomes were compared between treatment groups after propensity score matching. Results. Among 114,134 eligible STEMI patients, heparin alone was the least frequent anticoagulation strategy, used in 14.4% to 18.1% of cases per year. Bivalirudin alone nearly tripled during the study period, from 12.7% to 37.8% and surpassed that of heparin plus GPI by 2013. Bivalirudin alone performed better than heparin alone for mortality (4.7% vs 5.3%, p = 0.010), clinically apparent bleeding (5.7% vs 6.7%, p < 0.001), transfusion rates (4.1% vs 4.8%, p = 0.003) and mean length of stay (4.1 vs 4.2 days, p < 0.001). The in-hospital death rate was lower with heparin plus GPI than with heparin alone (4.9% vs 5.9%, p < 0.001), but clinically apparent bleeding was higher in heparin plus GPI than in heparin alone (9.4% vs 7.1%, p < 0.001). Conclusion: In patients hospitalized for STEMI undergoing PPCI, heparin alone is not commonly used and is inferior to bivalirudin for mortality, bleeding and length of stay outcomes. Heparin is also inferior to heparin plus GPI for ischemic protection but associated with less bleeding.

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.

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.