Glycoprotein IIb/IIIa Inhibitors Use Research Articles

Safety and effectiveness of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: insights from the SPUM-ACS study

Abstract Aims Data on Glycoprotein IIb/IIIa inhibitors (GPI) use in real world ACS patients following the introduction of potent P2Y12 inhibitors and newer generation stents are scant. Here, we aimed to assess the utilization, effectiveness, and safety of GPI in a large prospective cohort of contemporary ACS patients. Methods SPUM-ACS is a prospective, multicentre study in which ACS patients between 2009 and 2017 were recruited. The primary endpoint of the present study was major adverse cardiovascular events (MACE), a composite of all-cause death, non-fatal myocardial infarction (MI) and non-fatal stroke at one year. Any bleeding events, BARC 3-5 bleeding, and net adverse cardiovascular events (NACE) comprised the secondary endpoints. Results A total of 4395 ACS patients were included in the analysis. GPI-treated patients had more total coronary artery occlusion (56% vs 35%, p<0.001) and thrombus (60% vs 35%, p<0.001) at angiography. Among the propensity score matched (PSM) population (1992 patients equally split into two groups), GPI-treated patients showed lower MACE risk (PSM adjusted HR 0.70, 95% CI 0.49-0.99) but a higher risk of any (PSM adj HR 1.46, 95% CI 1.06-1.99) and major bleedings (PSM adj HR 1.73, 95% CI 1.09-2.76), resulting in a neutral effect on NACE (PSM adj HR 0.87, 95% CI 0.65-1.17). These results remained consistent across all subgroups. When including only patients treated with potent P2Y12, the incidence of MACE was not different between the two groups, (log rank p=0.50 and PSM adjusted HR 0.94, 95% CI 0.60-1.48). In the PSM population, GPI use (HR 0.76, 95% CI 0.59-0.99, p=0.04), TIMI 3 at the end of the procedure (HR 0.16, 95% CI 0.08-0.30, p<0.001) and potent P2Y12 inhibitor use (HR 0.70, 95% CI 0.49-0.99, p=0.04) were protective independent predictors of MACE at follow-up, while oral anticoagulation at discharge (4.48, 95% CI 2.10-9.52, p<0.001), multivessel disease (HR 1.95, 95% CI 1.09-3.48, p=0.02) and KILLIP class ≥ 2 at admission (HR 1.98, 95% CI 0.99-3.95, p=0.05) were adverse independent predictors. Conclusion In ACS patients undergoing PCI and broadly treated with potent P2Y12 inhibitors, GPI use reduced the risk of MACE at 1 year, while increasing the risk of major bleedings, with a neutral effect on NACE. The routine use of these pharmacological agents should be discouraged, while in selected patients GPI use should be considered following personalized balancing between ischaemic and bleeding risk.Events in PSM populationEvents in PSM population

Bivalirudin versus heparin in patients with or without bail-out GPI use: a pre-specified subgroup analysis from the BRIGHT-4 trial

BackgroundConflicting results comparing bivalirudin versus heparin anticoagulation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), in part due to the confounding effect of glycoprotein IIb/IIIa inhibitors (GPI). The aim of the study was to compare the safety and effectiveness of bivalirudin plus a post-PCI high-dose infusion vs heparin with or without bail-out GPI use.MethodsWe conducted a pre-specified subgroup analysis from the BRIGHT-4 trial that randomized 6016 STEMI patients who underwent primary PCI to receive either bivalirudin plus a post-PCI high-dose infusion for 2–4 h or heparin monotherapy. GPI use was only reserved as bail-out therapy for procedural thrombotic complications. The primary outcome was a composite of all-cause death or Bleeding Academic Research Consortium (BARC) types 3–5 bleeding at 30 days.ResultsA total of 5250 (87.4%) patients received treatment without GPI while 758 (12.6%) received bail-out GPI. Bail-out GPI use was associated with an increased risk of the primary outcome compared to non-GPI use (5.28% vs. 3.41%; adjusted hazard ratio (aHR), 1.62; 95% confidence interval (CI), 1.13–2.33; P = 0.009) and all-cause death (5.01% vs. 3.12%; aHR, 1.74; 95% CI, 1.20–2.52; P = 0.004) but not in the risk of BARC types 3–5 bleeding (0.53% vs. 0.48%; aHR, 0.90; 95% CI, 0.31–2.66; P = 0.85). Among patients without GPI use, bivalirudin was associated with lower rates of the primary outcome (2.63% vs. 4.21%; aHR, 0.55; 95% CI, 0.39–0.77; P = 0.0005), all-cause death (2.52% vs. 3.74%; aHR, 0.58; 95% CI, 0.41–0.83; P = 0.003), and BARC types 3–5 bleeding (0.15% vs. 0.81%; aHR, 0.19; 95% CI, 0.06–0.57; P = 0.003) compared with heparin. However, among patients requiring bail-out GPI, there were no significant differences observed in the rates of the primary outcome (5.76% vs. 4.87%; aHR, 0.77; 95% CI, 0.36–1.66; P = 0.50; Pinteraction = 0.07) or its individual components between bivalirudin and heparin groups.ConclusionsBivalirudin plus a post-PCI high-dose infusion was associated with significantly reduced 30-day composite rate of all-cause death or BARC types 3–5 bleeding compared with heparin monotherapy in STEMI patients undergoing primary PCI without GPI use. However, these benefits might be less pronounced in patients requiring bail-out GPI due to thrombotic complications during primary PCI.Trial registrationClinicalTrials.gov NCT03822975.

Safety and effectiveness of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: insights from the SPUM-ACS study.

Data on glycoprotein IIb/IIIa inhibitor (GPI) use in real-world acute coronary syndrome (ACS) patients following the introduction of potent P2Y12 inhibitors and newer-generation stents are scant. Here, we aimed to assess the utilization, effectiveness, and safety of GPI in a large prospective multicentre cohort of contemporary ACS patients. SPUM-ACS prospectively recruited patients presenting with ACS between 2009 and 2017. The primary endpoint of the present study was major adverse cardiovascular events (MACE), a composite of all-cause death, non-fatal myocardial infarction, and non-fatal stroke at 1 year. Secondary endpoints were defined as any bleeding events, Bleeding Academic Research Consortium (BARC) 3-5 bleeding, and net adverse cardiovascular events (NACE). A total of 4395 ACS patients were included in the analysis. GPI-treated patients had more total coronary artery occlusion (56%vs. 35%, P<0.001) and thrombus (60%vs. 35%, P<0.001) at angiography. Among the propensity score-matched (PSM) population (1992 patients equally split into two groups), GPI-treated patients showed lower risk of MACE [PSM adjusted hazard ratio (HR) 0.70, 95% CI 0.49-0.99], but a higher risk of any (PSM adjusted HR 1.46, 95% CI 1.06-1.99) and major bleedings (PSM adjusted HR 1.73, 95% CI 1.09-2.76), resulting in a neutral effect on NACE (PSM adjusted HR 0.87, 95% CI 0.65-1.17). These results remained consistent across all subgroups. In patients with ACS undergoing percutaneous coronary intervention and receiving potent P2Y12 inhibitors, we observed a reduced risk of MACE and an increased risk of major bleedings at 1 year in patients treated with GPI. Although the routine use of GPI is currently not recommended, they might be considered in selected patients following a personalized balancing between ischaemic and bleeding risks.

Use of Glycoprotein IIb-IIIa Inhibitors in Patients Undergoing Carotid Artery Stenting in the Vascular Quality Initiative

Antiplatelet therapies with thromboxane inhibitors and adenosine 5'-diphosphate antagonists have been widely used following carotid artery stenting (CAS). However, these therapies may not apply to patients who are intolerant or present acutely. Glycoprotein IIb/IIIa inhibitors (GPI) are a proposed alternative therapy in these patients; however, their use has been limited due to concerns of increased risk for intracranial bleeding. Thus, this study aims to assess the safety profile of GPI in patients undergoing CAS. All patients undergoing CAS in the Society of Vascular Surgery - Vascular Quality Initiative database from 2012 to 2021 was included and grouped into GPI versus non-GPI therapy (control). The primary outcome was in-hospital stroke or death, and secondary outcomes included in-hospital stroke/transient ischemic attack (TIA), death, myocardial infarction, and intracranial hemorrhage (ICH)/seizure. Patients were stratified by surgical approach (Transcarotid artery revascularization using flow reversal (TCAR) and transfemoral carotid artery stenting), and stepwise backward logistic regression analysis was conducted to evaluate major primary and secondary outcomes. A total of 50,628 patients underwent carotid revascularization. Of these, 4.4% of the patients received GPI. Mean age was similar between control versus GPI (71.35(9.67) vs. 71.36(10.20) years). Compared to the control group, patients who receive GPI are less likely to be on optimal medical therapy, including aspirin (83.0% vs. 88.1%), P2Y12 inhibitor (73.0% vs. 82.7%), and statin (82.3% vs. 86.0%) (All P<0.05). In addition, patients in the GPI group were more likely to undergo TCAR for carotid revascularization (52.2% vs. 48.4%) for emergent/urgent (29.4% vs. 16.8%) and symptomatic indications (55.5% vs. 49.7%) (All P<0.001). After stratifying by surgical approach, if patients underwent TFCAS and received a GPI, they were at increased odds of developing stroke/death (1.77(1.25-2.51)), death (odds ratio (OR) (95% CI): 1.67(1.07-2.61)), stroke/TIA (OR (95% confidence interval (CI)): 1.65(1.09-2.51)), and ICH/seizure (OR (95% CI): 2.13(1.23-3.68)) (All P<0.05). No difference was seen in outcomes between the 2 groups if undergoing TCAR. Patients who receive GPI were more likely to be symptomatic at presentation and less likely to be medically optimized before their carotid revascularization. Transfemoral access in patients receiving GPI was associated with increased odds of morbidity and mortality. However, this was not observed if undergoing TCAR. TCAR can be considered for its overall favorable results in high-risk patients who are not medically optimized.

Thrombus containing lesions strategies during primary percutaneous coronary interventions in ST-segment elevation myocardial infarction: insights from ORPKI National Registry

In the era of potent P2Y12 inhibitors, according to current guidelines, treatment with glycoprotein IIb/IIIa inhibitors (GPIs) should be limited to bail-out and/or highly thrombotic situations. Similarly, the recommendation for aspiration thrombectomy (AT) is downgraded to very selective use. We examine the prevalence, and predictors of GPI and AT use in STEMI patients referred to primary percutaneous coronary intervention (PCI). Data on 116,873 consecutive STEMI patients referred to primary PCI in Poland between 2015 and 2020 were analyzed. GPIs were administered in 29.3%, AT was used in 11.6%, and combined treatment with both in 6.1%. There was a mild trend toward a decrease in GPI and AT usage during the analyzed years. On the contrary, there was a rapid growth of the ticagrelor/prasugrel usage rate from 6.5 to 48.1%. Occluded infarct-related artery at baseline and no-reflow during PCI were the strongest predictors of GPI administration (OR 2.3; 95% CI 2.22–2.38 and OR 3.47; 95% CI 3.13–3.84, respectively) and combined usage of GPI and AT (OR 4.4; 95% CI 4.08–4.8 and OR 3.49; 95% CI 3.08–3.95 respectively) in a multivariate logistic regression model. Similarly, the administration of ticagrelor/prasugrel was an independent predictor of both adjunctive treatment strategies. In STEMI patients in Poland, GPIs are selectively used in one in four patients during primary PCI, and the combined usage of GPI and AT is marginal. Despite the rapid growth in potent P2Y12 inhibitors usage in recent years, GPIs are selectively used at a stable rate during PCI in highly thrombotic lesions.

Abstract 13639: Bivalirudin versus Heparin in Patients With STEMI Undergoing PCI: Individual-Patient-Data Pooled Analysis of the 6 Major Randomized Trials

Background: Given differences in prior trial designs, the treatment tradeoffs between bivalirudin and heparin in patients with STEMI undergoing PCI remain uncertain. Study-level meta-analyses lack granularity to provide conclusive answers or assess subgroups. Methods: We performed an individual-patient-data pooled analysis from all 6 large (n&gt;1000) RCTs of bivalirudin vs heparin in STEMI pts undergoing PCI (BRIGHT, EUROMAX, HEAT-PPCI, HORIZONS-AMI, MATRIX, and VALIDATE-SWEDEHEART). The primary efficacy outcome was the 30-day rate of all-cause mortality. Subgroup analyses were performed according to planned use of glycoprotein IIb/IIIa inhibitors (GPI), and administration of a post-PCI bivalirudin infusion. Results: A total of 15,254 patients with STEMI undergoing PCI were included (7,306 randomized to bivalirudin and 7,948 to heparin [43.6% with planned GPI use]). Thirty-day mortality was not significantly different between bivalirudin vs heparin (aHR: 0.80; 95% CI: 0.64, 1.01); 30-day cardiac mortality was reduced with bivalirudin (aHR: 0.72; 95% CI: 0.57, 0.91). There was a higher risk of 30-day MI (aHR: 1.29, 95% CI: 1.02, 1.64) and stent thrombosis (aHR: 1.42; 95 % CI: 1.05, 1.91) but lower risk of serious bleeding (aHR: 0.57 (0.47, 0.68) with bivalirudin vs heparin. At 1 year, net adverse clinical events were reduced with bivalirudin (aHR: 0.84; 95% CI: 0.77, 0.93) (Table). All-cause mortality was reduced with bivalirudin when a post-PCI infusion was used. A high-dose post-PCI infusion mitigated the 30-day MI and ST risks, irrespective of planned GPI use with heparin. Conclusions: In patients with STEMI undergoing PCI, procedural anticoagulation with bivalirudin did not reduce all-cause mortality. Cardiac mortality and serious bleeding were reduced with bivalirudin at the cost of increased rates of MI and ST. Full analyses will be presented at AHA 2022.

Association Between Platelet Glycoprotein IIb/IIIa Inhibition and In-Hospital Outcomes in ST-Elevation Myocardial Infarction Patients Treated with Coronary Thrombus Aspiration: Findings from the CCC-ACS Project.

Thrombus aspiration in ST-elevation myocardial infarction (STEMI) with high thrombus burden did not improve clinical outcomes. The clinical efficacy of the bailout use of platelet glycoprotein IIb/IIIa inhibitors (GPIs) in this clinical scenario remains unknown. We assessed associations between GPI use and in-hospital major bleeds, ischemic events, and mortality among STEMI patients treated with percutaneous coronary intervention (PCI) and thrombus aspiration in a nationwide acute coronary syndrome registry (the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project). A total of 5896 STEMI patients who received thrombus aspiration were identified, among which 56.3% received GPI therapy. In a 1-to-1 propensity-score-matched cohort, compared with STEMI patients not treated with GPI, GPI use was associated with a 69% increase in major in-hospital bleeds, with an odds ratio (OR) of 1.69, a 95% confidence interval (CI) of 1.08 to 2.65, and a nonsignificant reduction in ischemic events (OR: 0.61, 95% CI: 0.36 to 1.06), as well as a neutral effect on mortality (OR: 0.93, 95% CI: 0.55 to 1.58). However, among patients aged < 60years, GPI use was associated with a reduction in ischemic events (OR: 0.27, 95% CI: 0.08 to 0.98), and no significant increase in major bleeds was observed. In a nationwide registry, routine use of GPI following thrombus aspiration was not associated with reduced in-hospital ischemic events and mortality but at the cost of increased major bleeding. However, for patients aged < 60years, there may be a potential net benefit.

Glycoprotein IIb/IIIa inhibitor use in cardiogenic shock complicating myocardial infarction: The Portuguese Registry of Acute Coronary Syndromes

Introduction and objectivesCardiogenic shock (CS) complicates 5–10% of cases of myocardial infarction (MI). Whether glycoprotein IIb/IIIa inhibitors (GPIs) are beneficial in these patients is controversial. Our aim is to assess the prognostic impact of GPI use on in-hospital mortality and outcomes in patients with MI and CS undergoing percutaneous coronary intervention (PCI). MethodsBetween October 2010 and December 2019, 27578 acute coronary syndrome (ACS) patients were included in the multicenter Portuguese Registry of Acute Coronary Syndromes. Of these, 357 with an MI complicated by CS were included in the analysis and grouped based on whether they received GPI therapy (with GPI, n=107 and without GPI, n=250). The primary endpoint was in-hospital mortality. Secondary endpoints included successful PCI and in-hospital reinfarction and major bleeding. ResultsDemographics and cardiovascular risk factors did not differ between groups. ST-elevation MI patients were more likely to receive GPIs (95% vs. 83%, p=0.002). In-hospital mortality was similar between groups (OR 1.80, 95% CI 0.96–3.37). Only age and the use of inotropes or intra-aortic balloon pump were predictors of mortality. Also, no differences between groups were noted for successful PCI (OR 0.33, 95% CI 0.62–4.06), reinfarction (OR 0.77, 95% CI 0.15–3.90), or major bleeding (OR 1.68, 95% CI 0.75–3.74). ConclusionThe use of GPIs in the context of MI with CS did not significantly impact in-hospital outcomes.

Use of Glycoprotein IIb-IIIa Inhibitors in patients undergoing Carotid Artery Stenting

Antiplatelet therapies with thromboxane inhibitors and adenosine 5'-diphosphate antagonists have been widely used following carotid artery stenting (CAS). These therapies may not be applicable in patients that are intolerant or nonresponders. Glycoprotein IIb/IIIa inhibitors (GPI) are a proposed alternative therapy for these patients, however, its use has been limited due to concern of increased hemorrhage. Thus, the purpose of this study is to assess the safety profile of GPI in patient’s undergoing transfemoral CAS (TF-CAS) and transcarotid artery revascularization using flow-reversal (TCAR).

European Stroke Organisation guidelines on treatment of patients with intracranial atherosclerotic disease.

The aim of the present European Stroke Organisation guideline is to provide clinically useful evidence-based recommendations on the management of patients with intracranial atherosclerotic disease (ICAD). The guidelines were prepared following the Standard Operational Procedure of the European Stroke Organisation guidelines and according to GRADE methodology. ICAD represents a major cause of ischemic stroke worldwide, and patients affected by this condition are exposed to a high risk for future strokes and other major cardiovascular events, despite best medical therapy available. We identified 11 relevant clinical problems affecting ICAD patients and formulated the corresponding Population Intervention Comparator Outcomes (PICO) questions. The first two questions refer to the asymptomatic stage of the disease, which is being increasingly detected thanks to the routine use of noninvasive vascular imaging. We were not able to provide evidence-based recommendations regarding the optimal detection strategy and management of asymptomatic ICAD, and further research in the field is encouraged as subclinical ICAD may represent a big opportunity to improve primary stroke prevention. The second block of PICOs (3-5) is dedicated to the management of acute large vessel occlusion (LVO) ischemic stroke caused by ICAD, a clinical presentation of this disease that is becoming increasingly relevant and problematic, since it is associated with more refractory endovascular reperfusion procedures. An operational definition of probable ICAD-related LVO is proposed in the guideline. Despite the challenging context, no dedicated randomized clinical trials (RCTs) were identified, and therefore the guideline can only provide with suggestions derived from observational studies and our expert consensus, such as the escalated use of glycoprotein IIb-IIIa inhibitors and angioplasty/stenting in cases of refractory thrombectomies due to underlying ICAD. The last block of PICOs is devoted to the secondary prevention of patients with symptomatic ICAD. Moderate-level evidence was found to recommend against the use of oral anticoagulation as preferred antithrombotic drug, in favor of antiplatelets. Low-level evidence based our recommendation in favor of double antiplatelet as the antithrombotic treatment of choice in symptomatic ICAD patients, which we suggest to maintain during 90 days as per our expert consensus. Endovascular therapy with intracranial angioplasty and or stenting is not recommended as a treatment of first choice in high-grade symptomatic ICAD (moderate-level evidence). Regarding neurosurgical interventions, the available evidence does not support their use as front line therapies in patients with high-grade ICAD. There is not enough evidence as to provide any specific recommendation regarding the use of remote ischemic conditioning in ICAD patients, and further RCTs are needed to shed light on the utility of this promising therapy. Finally, we dedicate the last PICO to the importance of aggressive vascular risk factor management in ICAD, although the evidence derived from RCTs specifically addressing this question is still scarce.

494 Glycoprotein IIB/IIIA inhibitors may modulate the clinical benefit of radial access as compared to femoral access in primary percutaneous coronary intervention: a meta-regression and a meta-analysis of randomized trials

Abstract Aims Several randomized controlled trials (RCTs) consistently reported better clinical outcomes with radial as compared to femoral access for primary percutaneous coronary intervention (PCI). Nevertheless, heterogeneous use of potent antiplatelet drugs, such as Gp IIb/IIIa inhibitors (GPI), across different studies could have biased the results in favour of radial access. We performed an updated meta-analysis and meta-regression of RCTs in order to appraise whether the use of GPI had an impact on pooled estimates of clinical outcomes according to vascular access. Methods and results We computed pooled estimates by the random effects model for the following outcomes: mortality, major adverse cardiovascular events (death, myocardial infarction, stroke, and target vessel revascularization), and major bleedings. Additionally, we performed meta-regression analysis to investigate the impact of GPI use on pooled estimates of clinical outcomes. We analysed 14 randomized controlled trials and 11 090 patients who were treated by radial (5497) and femoral access (5593), respectively. Radial access was associated with better outcomes for mortality [risk difference 0.01 (0.00, 0.01), P = 0.03], MACE [risk difference 0.01 (0.00, 0.02), P = 0.003], and major bleedings [risk difference 0.01 (0.00, 0.02), P = 0.02]. At meta-regression, we observed a significant correlation of mortality with both GPI use (P = 0.011) and year of publication (P = 0.0073), whereas no correlation was observed with major bleedings. Conclusions In this meta-analysis, the use of radial access for primary PCI was associated with better clinical outcomes as compared to femoral access. However, the effect size on mortality was modulated by GPI rate, with greater benefit of radial access in studies with larger use of these drugs.

Bivalirudin Versus Heparin Monotherapy in ST-Segment-Elevation Myocardial Infarction.

Bivalirudin was not superior to unfractionated heparin in patients with myocardial infarction (MI) treated with percutaneous coronary intervention and no planned use of GPI (glycoprotein IIb/IIIa inhibitors) in contemporary clinical practice of radial access and potent P2Y12-inhibitors in the VALIDATE-SWEDEHEART randomized clinical trial (Bivalirudin Versus Heparin in STEMI and NSTEMI Patients on Modern Antiplatelet Therapy-Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry). In this prespecified separately powered subgroup analysis, we included patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention with the primary composite end point of all-cause death, MI, or major bleeding event within 180 days. Among the 6006 patients enrolled in the trial, 3005 patients with ST-segment-elevation MI were randomized to receive bivalirudin or heparin. The mean age was 66.8 years. According to protocol recommendations, 87% were treated with potent oral P2Y12-inhibitors before start of angiography and radial access was used in 90%. GPI was used in 51 (3.4%) and 74 (4.9%) of patients randomized to receive bivalirudin and heparin, respectively. The primary end point occurred in 12.5% (187 of 1501) and 13.0% (196 of 1504; hazard ratio [HR], 0.95 [95% CI, 0.78-1.17], P=0.64) with consistent results in all major subgroups. All-cause death occurred in 3.9% versus 3.9% (HR, 1.00 [0.70-1.45], P=0.98), MI in 1.7% versus 2.2% (HR, 0.76 [0.45-1.28], P=0.30), major bleeding in 8.3% versus 8.0% (HR, 1.04 [0.81-1.33], P=0.78), and definite stent thrombosis in 0.5% versus 1.3% (HR, 0.42 [0.18-0.96], P=0.04). In patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention with radial access and receiving current recommended treatments with potent P2Y12-inhibitors rate of the composite of all-cause death, MI, or major bleeding was not lower in those randomized to receive bivalirudin as compared with heparin. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02311231.

Impact of SARS-CoV-2 positivity on clinical outcome among STEMI patients undergoing mechanical reperfusion: Insights from the ISACS STEMI COVID 19 registry

Background and aimsSARS-Cov-2 predisposes patients to thrombotic complications, due to excessive inflammation, endothelial dysfunction, platelet activation, and coagulation/fibrinolysis disturbances. The aim of the present study was to evaluate clinical characteristics and prognostic impact of SARS-CoV-2 positivity among STEMI patients undergoing primary percutaneous coronary intervention (PPCI). MethodsWe selected SARS-CoV-2 positive patients included in the ISACS-STEMI COVID-19, a retrospective multicenter European registry including 6609 STEMI patients treated with PPCI from March 1st until April 30th, in 2019 and 2020. As a reference group, we randomly sampled 5 SARS-Cov-2 negative patients per each SARS-CoV-2 positive patient, individually matched for age, sex, and hospital/geographic area. Study endpoints were in-hospital mortality, definite stent thrombosis, heart failure. ResultsOur population is represented by 62 positive SARS-CoV-2 positive patients who were compared with a matched population of 310 STEMI patients. No significant difference was observed in baseline characteristics or the modality of access to the PCI center. In the SARS-CoV-2 positive patients, the culprit lesion was more often located in the RCA (p < 0.001). Despite similar pre and postprocedural TIMI flow, we observed a trend in higher use of GP IIb-IIIa inhibitors and a significantly higher use of thrombectomy in the SARS-CoV-2 positive patients. SARS-CoV-2 positivity was associated with a remarkably higher in hospital mortality (29% vs 5.5%, p < 0.001), definite in-stent thrombosis (8.1% vs 1.6%, p = 0.004) and heart failure (22.6% vs 10.6%, p = 0.001) that was confirmed after adjustment for confounding factors. ConclusionsOur study showed that among STEMI patients, SARS-CoV-2 positivity is associated with larger thrombus burden, a remarkably higher mortality but also higher rates of in-stent thrombosis and heart failure.

Glycoprotein IIb/IIIa Inhibitors May Modulate the Clinical Benefit of Radial Access as Compared to Femoral Access in Primary Percutaneous Coronary Intervention: A Meta-Regression and Meta-Analysis of Randomized Trials.

Objectives Several randomized controlled trials (RCTs) consistently reported better clinical outcomes with radial as compared to femoral access for primary percutaneous coronary intervention (PCI). Nevertheless, heterogeneous use of potent antiplatelet drugs, such as Gp IIb/IIIa inhibitors (GPI), across different studies could have biased the results in favor of radial access. We performed an updated meta-analysis and meta-regression of RCTs in order to appraise whether the use of GPI had an impact on pooled estimates of clinical outcomes according to vascular access. Methods We computed pooled estimates by the random-effects model for the following outcomes: mortality, major adverse cardiovascular events (death, myocardial infarction, stroke, and target vessel revascularization), and major bleedings. Additionally, we performed meta-regression analysis to investigate the impact of GPI use on pooled estimates of clinical outcomes. Results We analyzed 14 randomized controlled trials and 11090 patients who were treated by radial (5497) and femoral access (5593), respectively. Radial access was associated with better outcomes for mortality (risk difference 0.01 (0.00, 0.01), p=0.03), MACE (risk difference 0.01 (0.00, 0.02), p=0.003), and major bleedings (risk difference 0.01 (0.00, 0.02), p=0.02). At meta-regression, we observed a significant correlation of mortality with both GPI use (p=0.011) and year of publication (p=0.0073), whereas no correlation was observed with major bleedings. Conclusions In this meta-analysis, the use of radial access for primary PCI was associated with better clinical outcomes as compared to femoral access. However, the effect size on mortality was modulated by GPI rate, with greater benefit of radial access in studies with larger use of these drugs.

Intracoronary bolus of glycoprotein IIb/IIIa inhibitor as bridging or adjunctive strategy to oral P2Y12 inhibitor load in the modern setting of ST-elevation myocardial infarction.

In the acute management of ST-elevation myocardial infarction (STEMI), glycoprotein IIb/IIIa inhibitors (GPIs) bolus not followed by intravenous infusion is potentially advantageous given their fast onset and offset of action, but clinical evidence in a contemporary setting is limited. We collected data from consecutive STEMI patients admitted to the cardiac catheterization laboratory of the IRCCS A. Gemelli University Polyclinic Foundation from October 2017 to September 2019. Out of 423 consecutive STEMI patients, 297 met the inclusion and exclusion criteria and were included in the study. Of them, 107/297 (36%) received an intracoronary GPI bolus-only during primary percutaneous coronary intervention (PPCI) not followed by intravenous infusion and 190/297 (64%) received standard antithrombotic therapy. Of the 107 GPI-treated, 22/107 (21%) had P2Y<inf>12</inf> inhibitor pretreatment (adjunctive strategy) and 85/107 (79%) did not (bridging strategy). During hospital staying, there was no difference in the primary safety endpoint of TIMI major+minor bleeding (P=0.283), TIMI major (P=0.267) or TIMI minor (P=0.685) bleeding between groups. No stroke event occurred in the GPI group. Despite patients receiving GPI having a significantly higher intraprocedural ischemic burden, no significant differences were found in the efficacy outcomes between groups. Consistent findings were observed for patients receiving GPIs bolus before (bridging strategy) or after (adjunctive strategy) P2Y<inf>12</inf> inhibitors, compared to those receiving standard therapy. Multivariate logistic regression analyses did not find any independent predictors significantly associated to the primary and secondary composite endpoints. In a contemporary real-world population of STEMI patients undergoing PPCI, the use of intracoronary GPIs bolus-only in selected patients at high ischemic risk is safe and could represent a useful antithrombotic strategy both in those pretreated and in those naïve to P2Y<inf>12</inf> inhibitors.

Primary percutaneous coronary intervention in nonagenarian patients

Abstract Background Given the continuous increase in life expectancy, elderly patients with ST segment elevation myocardial infarction (STEMI) are becoming a growing proportion of those referred for primary percutaneous coronary intervention (pPCI). However, this population is usually excluded from randomized trials and limited data are available to guide clinical decisions. The aim of this study-level meta-analysis was to describe and analyze the determinants of outcomes in this population. Methods We searched the literature for studies reporting ischemic and hemorrhagic outcomes and/or mortality in nonagenarian patients undergoing pPCI. An analysis of the heterogeneity between studies in outcome reports was performed with I2 test. A univariate meta-regression analysis was conducted to explore the relationship between outcomes of interest and classic cardiovascular risk factors, gender, previous myocardial infarction (MI), MI location, PCI characteristics, hemodynamic instability, vascular access, intra-aortic balloon pump (IABP) and Glycoprotein IIb/IIIa inhibitor (GPI) use. Results Overall, 15 observational studies met our inclusion criteria, with a total of 6787 patients; mean age was 92.4 and 35% were male. The incidence of in-hospital death was 21.3%, 1.4% of our population suffered an in-hospital ischemic stroke and 11.1% faced acute renal failure; in-hospital major bleedings affected 1.7% of the population, but blood-transfusion was needed in 6.9%. Long-term mortality rate was 21.5%. Killip III-IV at admission was related with increased in-hospital mortality (β: 0.2%; p: 0.041), but lower incidence of ARF (β: −0.6%; p: 0.004). Angiographic success was associated with a lower incidence of long-term all-cause mortality (β: −1.7%; p: 0.017) and higher incidence of ARF (β: 1.7%, p&amp;lt;0.001). A higher number of coronary stents implanted was associated with a lower incidence of long-term all-cause mortality (β: −73%; p: 0.01). A higher long-term all-cause mortality was related with male gender (β: 0.9%; p: 0.027) and previous MI (β: 1.5%; p: 0.007). Diabetes was associated with a lower incidence of long-term all-cause mortality (β: −0.8%; p: 0.014) despite a higher incidence of in-hospital blood transfusion (β: 0.5%, p: 0.05), while a history of MI (β: 0.1%; p: 0.049), as well as the use of GPI (β: 0.04) was related with a higher incidence of in-hospital major bleeding. The use of IABP was related with a lower incidence of long-term all-cause death (β: 6.5%; p&amp;lt;0.001) and in-hospital major bleeding (β: −0.4%; p: 0.038). Discussion Our meta-analysis, pooling the largest cohort of nonagenarians undergoing pPCI confirms the feasibility of urgent percutaneous coronary intervention also in this frail population. In particular, although angiographic success increased the incidence of in-hospital ARF, it was associated with a higher long-term survival underling the pivotal role of myocardial reperfusion. Funding Acknowledgement Type of funding source: None

Safety and benefit of Glycoprotein IIb/IIIa inhibitors in out of hospital cardiac arrest patients treated with percutaneous coronary intervention

BackgroundOut of hospital cardiac arrest (OHCA) patients requiring percutaneous coronary intervention (PCI) are at higher risk of both stent thrombosis and bleeding. The use of aggressive antiplatelet therapy could lead to a higher risk of bleeding in these patients. Indeed, data on glycoprotein IIb/IIIa inhibitor (GPi) use in this specific indication is scarce. AimWe sought to evaluate the benefit and safety of GPi use in OHCA patients requiring PCI. Methods and resultsBetween January 2007 and December 2017, we retrospectively included all consecutive patients treated with PCI for an OHCA from cardiac cause. Clinical, procedural data and in-hospital outcomes were collected. Three hundred and eighty-five patients were included. GPi were administrated in 41.3% of cases (159 patients). Patients who received GPi were younger, had less prior PCI, more often a TIMI 0 or 1 flow before PCI and thromboaspiration use. There were no differences regarding in-hospital definite stent thrombosis among the two groups (11.9% in the GPi group vs 7.1% in the non-GPi group, p = 0.10) or in-hospital mortality (48.6% vs 49.3%, p = 0.68). The incidence of any bleeding (33.3% vs. 19.6%; p = 0.002), and major bleeding (BARC 3−5) (21.9% vs. 16.8%; p = 0.007) was significantly higher in patients receiving GPi. Indeed, using multivariate analysis, GPi use was predictor of major bleeding (OR: 1.81; 95% CI: 1.06−3.08; p = 0.03). ConclusionsIn patients treated with PCI for OHCA from cardiac cause, GPi use was associated with an increased risk of major bleeding events, without difference on in-hospital stent thrombosis or death.

Safety and Efficacy of Glycoprotein IIb/IIIa Inhibitors in Patients With Acute Myocardial Infarction in the Presence of Intracoronary Thrombus: An Analysis From the Grand Drug-eluting Stent Registry

PurposeTo evaluate the safety and efficacy of glycoprotein IIb/IIIa inhibitors (GPIs) in patients with acute myocardial infarction (AMI) in the presence of intracoronary thrombus undergoing percutaneous coronary interventions. MethodsThis study, performed from January 1, 2004, to November 31, 2014, at 55 centers in Korea, was based on the Grand Drug-Eluting Stent registry, which is a Korean, nationwide, multicenter, pooled registry of drug-eluting stents. The registry enrolled all-comers without any exclusion criteria except patient withdrawal of consent. A total of 1329 patients with AMI who had an overt intracoronary thrombus at the initial coronary angiography were analyzed. The efficacy end point was a 1-year major adverse cardiovascular event, defined as a composite of all death, myocardial infarction, target lesion revascularization, and stent thrombosis. The primary safety end point was any 30-day bleeding event. FindingsGPIs were associated with a significantly higher rate of any bleeding events at 30 days (0.9% vs 2.9% in the non-GPI and GPI groups, respectively; P = 0.015), whereas GPI use was the only significant independent predictor of 30-day bleeding events by multivariable Cox proportional hazards regression analysis (hazard ratio = 4.76; 95% CI, 1.66–13.64; P = 0.004). Regarding the efficacy end points, no significant differences were noted according to GPI use (7.0% vs 9.0%, P = 0.287), and GPI use has no significant effect on 1-year major adverse cardiovascular events (hazard ratio = 1.33; 95% CI, 0.82–2.15; P = 0.253). ImplicationsEarly upstream use of GPIs should not be considered even in the presence of an intracoronary thrombotic occlusion. ClinicalTrials.gov identifier: NCT03507205.

Antithrombotic regimens for percutaneous coronary intervention of the left main coronary artery: The EXCEL trial.

We compared the effect of bivalirudin or heparin and use or nonuse of glycoprotein IIb/IIIa inhibitors (GPI) on the outcome of left main coronary artery (LMCA) percutaneous coronary intervention (PCI) in the randomized EXCEL trial. The optimal antithrombotic regimen to support PCI of the LMCA remains controversial because of low representation of this subset in clinical trials. The PCI cohort (n = 928) in EXCEL was divided according to bivalirudin versus heparin antithrombin treatment and compared for the primary composite endpoint of death, myocardial infarction (MI), or stroke at 30 days and 5 years. Bivalirudin was used in 319 patients (34.4%). The composite endpoint at 30 days occurred in 7.2% versus 3.8% bivalirudin and heparin patients, respectively, p = .02; at 5 years, the composite endpoint occurred in 26.3% versus 19.9% bivalirudin and heparin patients, respectively, p = .02. Major bleeding was more frequent in bivalirudin patients (4.1% versus 1.3%, p = .008). There were no differences in stent thrombosis between the groups. Bivalirudin use was an independent predictor of the 30-day composite endpoint (OR 2.88, 95% CI 1.28-6.48, p = .01) but not of the 5-year composite endpoint (OR 1.30, 95% CI 0.84-2.02, p = .23). GPI use was infrequent (n = 67, 7.2%) and was not associated with adverse outcomes. Among patients undergoing LMCA PCI in the EXCEL trial, procedural use of bivalirudin was associated with greater rates of periprocedural MI and the 30-day composite endpoint without reducing bleeding complications. Five-year outcomes were similar. GPIs were used infrequently and were not associated with clinical outcomes.

Bivalirudin Versus Heparin During Intervention in Acute Coronary Syndrome: A Systematic Review of Randomized Trials.

Introduction: Bivalirudin and heparin are the two most commonly used anticoagulants used during Percutaneous Coronary Intervention (PCI). The results of Randomized Controlled Trials (RCTs) comparing bivalirudin versus heparin monotherapy in the era of radial access are controversial, questioning the positive impact of bivalirudin on bleeding. The purpose of this systematic review is to summarize the results of RCTs comparing the efficacy and safety of bivalirudin versus heparin with or without Glycoprotein IIb/IIIa Inhibitors (GPI).Methods:This systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA statements for reporting systematic reviews. We searched the National Library of Medicine PubMed, Clinicaltrial.gov and the Cochrane Central Register of Controlled Trials to include clinical studies comparing bivalirudin with heparin in patients undergoing PCI. Sixteen studies met inclusion criteria and were reviewed for the summary.Findings: Several RCTs and meta-analyses have demonstrated the superiority of bivalirudin over heparin plus routine GPI use in terms of preventing bleeding complications but at the expense of increased risk of ischemic complications such as stent thrombosis. The hypothesis of post- PCI bivalirudin infusion to mitigate the risk of acute stent thrombosis has been tested in various RCTs with conflicting results. In comparison, heparin offers the advantage of having a reversible agent, of lower cost and reduced incidence of ischemic complications.Conclusion:Bivalirudin demonstrates its superiority over heparin plus GPI with better clinical outcomes in terms of less bleeding complications, thus making it as anticoagulation of choice particularly in patients at high risk of bleeding. Further studies are warranted for head to head comparison of bivalirudin to heparin monotherapy to establish an optimal heparin dosing regimen and post-PCI bivalirudin infusion to affirm its beneficial effect in reducing acute stent thrombosis.