Glycoprotein IIb/IIIa Inhibitors Research Articles

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).

Endovascular Treatment of an Elderly Diabetic Patient with a Circular Myocardial Infarction in Cardiogenic Shock Complicated by Stent Thrombosis

The most common cause of cardiogenic shock (CS) is acute myocardial infarction (AMI), which is diagnosed in approximately 5–8% of patients hospitalized for AMI and is more common in patients with acute ST-segment elevation myocardial infarction (STEMI). CS is caused by severe myocardial dysfunction, which leads to a decrease in cardiac output, hypoperfusion of the end organs, and hypoxia. Mortality in diabetic patients with AMI is high. Besides the fact that type 2 diabetes mellitus (DM2) contributes to the progression of coronary atherosclerosis, coronary pathology in this category of patients occurs against the background of a specific diabetic myocardial lesion – diabetic cardiomyopathy. Against the background of cardiomyopathy, acute heart failure is more often developed with a decrease in global myocardial contractility up to CS, which increases hospital-acquired mortality in MI by more than 15 times. The increased risk of death observed in patients with DM2 in the acute period of myocardial infarction (MI) persists for several years, and therefore, at present, in patients with the acute coronary syndrome (ACS) and diabetes, an early invasive strategy is preferable to a conservative strategy. The SHOCK (Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock) trial demonstrated that in patients with CS complicating AMI, emergency revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) improved long-term survival when compared with initial intensive medical therapy. However, in the CULPRIT-SHOCK (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock) study, stenting of non-infarct-dependent coronary arteries in CS increases the risks of major cardiac events, as well as the number of repeated revascularizations within 30 days and 1 year. Patients with multivessel lesions, in most cases, are elderly patients (75–90 years old) who have age restrictions on taking the loading dose at the prehospital stage. Such a loading dose of clopidogrel may not be sufficient to saturate the patient in fact, despite optimal epicardial recanalization, a large proportion of patients still experience impaired reperfusion and in-stent thrombosis. A large body of evidence has been accumulated on the benefits of glycoprotein (GP) IIb-IIIa inhibitors in terms of prevention of stent thrombosis, and benefits in mortality, especially among high-risk patients, and as an upstream strategy.

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.

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). 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, it’s use has been limited owing 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).

Intracoronary pharmacological therapy versus aspiration thrombectomy in STEMI (IPAT-STEMI): A systematic review and meta-analysis of randomized trials.

BackgroundThrombus load in STEMI patients remains a challenge in practice. It aggravates coronary obstruction leading to impaired myocardial perfusion, worsened cardiac function, and adverse clinical outcomes. Various strategies have been advocated to reduce thrombus burden.ObjectivesThis meta-analysis aimed to evaluate the effectiveness of intracoronary-administered thrombolytics or glycoprotein IIb/IIIa inhibitors (GPI) in comparison with aspiration thrombectomy (AT) as an adjunct to percutaneous coronary intervention (PCI) among patients presenting with ST-segment elevation myocardial infarction (STEMI).MethodsA comprehensive literature search for randomized trials that compared intracoronary-administered thrombolytics or GPI with AT in STEMI patients who underwent PCI, was conducted using various databases (e.g., MEDLINE, EMBASE, CENTRALE). Primary outcome was procedural measures (e.g., TIMI flow grade 3, TIMI myocardial perfusion grade (TMPG) 3, Myocardial blush grade (MBG) 2/3, ST-segment resolution (STR)).ResultsTwelve randomized trials enrolled 1,466 patients: 696 were randomized to intracoronary-administered pharmacological interventions and 553 to AT. Patients randomized to PCI alone were excluded. Thrombolytics significantly improved TIMI flow grade 3 (odds ratio = 3.71, 95% CI: 1.85–7.45), complete STR (odds ratio = 3.64, 95% CI: 1.60–8.26), and TMPG 3 (odds ratio = 5.31, 95% CI: 2.48–11.36). Thrombolytics significantly reduced major adverse cardiovascular events (MACE) (odds ratio = 0.29, 95% CI: 0.13–0.65) without increasing bleeding risk. Trial sequential analysis assessment confirmed the superiority of thrombolytics for the primary outcome. Intracoronary GPI, either alone or combined with AT, did not improve procedural or clinical outcomes.ConclusionsCompared with AT, intracoronary-administered thrombolytics significantly improved myocardial perfusion and MACE in STEMI patients.

The novel subcutaneously administered glycoprotein IIb/IIIa antagonist RUC-4 (Zalunfiban) did not cause thrombocytopenia in the phase 2a study of patients with ST-elevation myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Celecor Therapeutics Background/Introduction Thrombocytopenia is a rare but severe complication (0.5%-2.0%) of all currently available glycoprotein IIb/IIIa inhibitors (GPI). As thrombocytopenia is inherently linked to bleeding, careful consideration is mandated in ST-elevation myocardial infarction (STEMI) patients as they require multiple antithrombotic medications. Moreover, thrombocytopenia is associated with poor clinical outcomes in comparison to patients without thrombocytopenia. Thus, there is a need for safer GPIs that are not associated with drug-induced thrombocytopenia. Zalunfiban is a novel, second-generation GPI primarily designed for the pre-hospital phase to initiate target vessel reperfusion. In addition, Zalunfiban has a unique mechanism of action that locks the receptor into an inactive conformation, potentially decreasing the likelihood of developing thrombocytopenia. In healthy individuals and in patients with stable coronary artery disease treated with Zalunfiban, no thrombocytopenia was seen. Purpose To assess the occurrence of thrombocytopenia of Zalunfiban in STEMI patients. Methods This was a prospective, single centre, open-label, phase 2a study designed to assess the pharmacodynamics, pharmacokinetics, and tolerability of Zalunfiban in patients with STEMI undergoing primary percutaneous coronary intervention. The primary endpoint in this sub-analysis was the occurrence of thrombocytopenia, defined as a platelet count less than 150 × 10^9/L, as measured at 4 time points up to 72 hours after drug administration. Secondary analyses were laboratory assessments including haemoglobin, creatinine and liver function tests. Results A total of 27 patients received a weight-adjusted subcutaneous injection of Zalunfiban in escalating doses (0.075 mg/kg [n=8], 0.090 mg/kg [n=9], or 0.110 mg/kg [n=10]). No thrombocytopenia (0.0%) was observed within the first 72 hours post dose. Also, haemoglobin, creatinine and liver function tests were stable during hospitalisation. Conclusion In this sub-analysis Zalunfiban did not cause thrombocytopenia in the 27 patients enrolled in the study, which is in accord with the lack of thrombocytopenia in the 44 patients receiving Zalunfiban in the Phase 1 studies in healthy volunteers and stable angina patients. The ongoing CELEBRATE study, in which Zalunfiban is administered in the ambulance, is scheduled to enrol 1667 STEMI patients and thus will provide important additional information on Zalunfiban safety and efficacy.

Primary Percutaneous Coronary Intervention with High-Bolus Dose Tirofiban: The FASTER (Favorite Approach to Safe and Effective Treatment for Early Reperfusion) Multicenter Registry.

Objectives To investigate the safety and clinical efficacy of tirofiban during primary percutaneous coronary interventions (pPCI). Background Gp IIb/IIIa inhibitors (GPI) use during pPCI has declined over years, mainly for the increased hemorrhagic risk associated to their use and for the availability of potent, fast-acting oral antiplatelet drugs. However, several pharmacodynamic studies showed suboptimal platelet inhibition with P2Y12-blockers, such as prasugrel or ticagrelor. Methods Patients with ST-segment elevation myocardial infarction (STEMI) undergoing pPCI were prospectively enrolled in a multicenter registry conducted in high-volume centers in Italy. All patients received intraprocedural tirofiban. The primary safety endpoint was the occurrence of in-hospital bleedings according to the Bleeding Academic Research Consortium definition. In-hospital major adverse coronary events (MACE, defined as death, reinfarction, stent thrombosis, and target vessel revascularization), final TIMI flow, myocardial blush grade, and ST-segment resolution were also evaluated. Results A total of 472 patients (mean age 61 ± 11 years, 83% males) were enrolled in 16 Italian centers from October 2015 to June 2018. Mean basal thrombus grade score was 3.47 ± 1.25. PCI was performed by transradial approach in 88% of patients. We observed a very low rate of 30 days BARC bleedings (2.1%) and MACE (0.8%). Complete (>70%) ST-segment resolution was observed in 67% of patients. Conclusions In the FASTER registry, the use of tirofiban during primary PCI, performed with a transradial approach in most cases, in patients with high thrombus burden was associated with high rates of complete ST-segment resolution and low rates of in-hospital bleeding and MACE.

Efficacy and safety of abciximab versus tirofiban in addition to ticagrelor in STEMI patients undergoing primary percutaneous intervention

Platelet glycoprotein IIb/IIIa inhibitors (GPIs) have been part of the adjuvant treatment of acute coronary syndrome for years. However, real-life data regarding the efficacy and safety of GPIs under the current indications are lacking in the setting of potent platelet inhibition. The objectives were to assess the efficacy and safety of abciximab versus tirofiban in patients with ST-elevation acute myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) and pretreated with ticagrelor, and to identify independent predictor factors of efficacy, bleeding and platelet drop. Three hundred sixty-two patients were divided by GPI administered. Clinical, laboratory, angiographic and outcome characteristics were compared. The primary objective was a composite efficacy endpoint (death from any cause, nonfatal myocardial infarction and nonfatal stroke) at 30 days. The secondary objectives were its individual components, safety (bleeding) and the impact on platelet count during hospital stay. The composite efficacy endpoint was similar in the abciximab and tirofiban groups (6.1% vs 7.3%; p = .632). There were also no differences in cardiovascular death (2.5% vs 2.4%; p = .958), nonfatal myocardial infarction (3% vs 4.3%; p = .521) and nonfatal stroke (0.5% vs 1.8%; p = .332). Tirofiban administration was associated with a higher incidence of bleeding (11.6% vs 22%; p = .008) with no differences in BARC ≥ 3b bleeding (3.6 vs 2.5%; p = .760). In STEMI patients undergoing PPCI with ticagrelor, abciximab and tirofiban had similar rates in the composite efficacy endpoint at 30 days. The 30-day bleeding rate was significantly higher in the tirofiban group. Tirofiban administration was an independent predictor of both bleeding and platelet count drop.

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.

Abstract 9500: One-Year Safety and Effectiveness of Bivalirudin in Patients Undergoing Elective Percutaneous Coronary Intervention

Introduction: A lot of large studies (HORIZONS-AMI, BRIGHT, EUROMAX, etc.) have shown that bivalirudin in acute myocardial infarction patients undergoing primary percutaneous coronary intervention (PCI) could reduce the bleeding while prevent thrombosis. However, data on patients undergoing elective PCI are lacking which warrants research attention. Methods: 1152 patients undergoing elective PCI anticoagulated with bivalirudin and 10251 patients anticoagulated with UFH were performed propensity score matching at 1:2 ratio. Finally, 957 and 1713 patients were enrolled in bivalirudin and UFH group respectively. The safe endpoints were according to the Bleeding Academic Research Consortium (BARC). The effective endpoint was major adverse cardiac and cerebrovascular events (MACCE). Results: During one-year follow-up, multivariate Cox analysis showed bivalirudin group had a reduction in the risk of BARC 2, 3 or 5 bleeding (HR: 0.580, 95% CI: 0.340-0.989, P=0.045), but not in the risk of BARC 3 or 5 bleeding (P=0.214) compared with UFH with or without glycoprotein IIb/IIIa inhibitors (GPI) group. To further study, we also analyzed 254 (14.8%) patients with GPI in UFH group and then found the risk of BARC 2, 3 or 5 bleeding in bivalirudin group reduced (P=0.001). As for MACCE, there was no significant difference between bivalirudin group and UFH with or without GPI group (P=0.159). Moreover, there was also no significant difference in the risk of death, revascularization, intrastent thrombosis or stroke, but a reduction in the risk of MI between bivalirudin group and UFH with or without GPI group (P=0.002). Conclusions: In patients undergoing elective PCI, bivalirudin significantly reduced the risk of BARC 2, 3 or 5 bleeding, but not that of BARC 3 or 5 bleeding compared UFH with or without GPI. No significant difference in MACCE between two groups, while bivalirudin significantly reduced the risk of MI.

Intralesional delivery of glycoprotein IIb/IIIa inhibitors in acute myocardial infarction: Review and recommendations.

Plaque rupture leads to a cascade of events culminating in collagen disruption, tissue factor release, platelet activation and thrombus formation. Pro-inflammatory conditions, hyperglycemia and smoking predispose to high thrombus burden (HTB) which is an independent predictor of slow or no-reflow. In patients with acute myocardial infarction (AMI), glycoprotein IIb/IIIa inhibitors (GPI) reduce thrombus burden and improve myocardial perfusion. These agents are typically administered systemically via the intravenous route or locally via an intracoronary (IC) route. However, as higher local concentrations of GPI are associated with enhanced platelet inhibition, intralesional (IL) GPI administration may be particularly effective in cases of HTB. Modest-sized randomized trials comparing IL and IC GPI delivery have reported conflicting outcomes. Some trials have demonstrated improved coronary flow and myocardial perfusion with reduced major adverse cardiac events with IL compared with IC GPI administration, whereas others have shown no significant benefits. Furthermore, although no direct comparison has been made between IL delivery using an aspiration catheter, microcatheter or a dedicated balloon-based "weeping" infusion-catheter, improved outcomes have been most consistent following GPI administration at the site of the lesion and thrombus with the dedicated infusion catheter. This review provides an update on the role and outcomes of IL GPI administration in patients with AMI and HTB. Based on the evidence we offer an algorithm demonstrating when to consider IL administration in patients with AMI undergoing intervention. We conclude with a perspective on the management of patients with STEMI and COVID-19 in whom a prothrombotic state often results in HTB.

Safety and efficacy of prophylactic tirofiban infusion for acute intracranial intraprocedural stent thrombosis

Periprocedural antithrombotic management with glycoprotein IIb/IIIa inhibitors (GPI) for intracranial artery stenting is still controversial. We sought to assess the safety and efficacy of prophylactic tirofiban infusion for acute intracranial intraprocedural stent thrombosis in routine clinical practice. From January 2013 to December 2019, consecutive patients treated with endovascular stenting for symptomatic intracranial atherosclerotic stenosis (ICAS) were identified and dichotomized by whether tirofiban was used. The efficacy and safety outcomes were compared by propensity score matching. A total of 160 consecutive patients in the tirofiban group and 177 patients in the non-tirofiban group were enrolled. Propensity score matching analysis selected 236 matched patients. One acute intraprocedural stent thrombosis (AIST) occurred in patients receiving prophylactic tirofiban, while 8 in the non-tirofiban group. The incidence of AIST in the tirofiban group was significantly lower than that in the non-tirofiban group (0.8% vs 6.8%, P = 0.039). The periprocedural ischemic events (8.5% vs 5.1%, P = 0.424), periprocedural intracranial hemorrhage (4.2% vs 0.8%, P = 0.219) and 30-day total mortality (3.4% vs 0%, P = 0.125) were not statistically different between the two groups. Compared with conventional stenting angioplasty without tirofiban, tirofiban prophylactic infusion can lower the incidence of AIST, without increasing the risk of periprocedural intracranial hemorrhage and 30-day total mortality. However, there is no superiority in reducing periprocedural ischemic events. The current study adds more important insights to the available clinical evidence on the use of tirofiban during stenting of ICAS.

Notre ennemi : le caillot. Thrombose coronaire : stratégie et arsenal thérapeutique

Intra coronary thrombus is frequently encountered during acute coronary syndromes revascularisation procedures. It can also be encountered during angioplasty procedures in a stable angina context, although at a much lesser frequency.In both situations, it harbors a risk of poor angiographic result and poor prognosis. Intracoronnary thrombus may cause coronary occlusion at the angioplasty site or distal embolic flow obstruction. Per procedure thrombus prevention rests on an prior optimal anti thrombotic treatment and in some circumstances the choice to defer the revascularisation procedure in the complex high risk setting. Treating the initiated thrombus remains controversial concerning thrombectomy and GPIIBIIIa inhibitors which are still in use in common practice. No reflow phenomenon is a particularly complex setting during cornary angioplasties, partially but not solely related to a thrombotic complication. It's treatment remains unclear in the absence of related oriented studies.The current mechanical and pharmacological antithrombotic therapies must remain common practice and used appropriately as of the clinical and angiographic setting, until further scientific outbrakes.

Reperfusion After Fibrinolytic Therapy (RAFT): An open-label, multi-centre, randomised controlled trial of bivalirudin versus heparin in rescue percutaneous coronary intervention.

BackgroundThe safety and efficacy profile of bivalirudin has not been examined in a randomised controlled trial of patients undergoing rescue PCI.ObjectivesWe conducted an open-label, multi-centre, randomised controlled trial to compare bivalirudin with heparin ± glycoprotein IIb/IIIa inhibitors (GPIs) in patients undergoing rescue PCI.MethodsBetween 2010–2015, we randomly assigned 83 patients undergoing rescue PCI to bivalirudin (n = 42) or heparin ± GPIs (n = 41). The primary safety endpoint was any ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) bleeding at 90 days. The primary efficacy endpoint was infarct size measured by peak troponin levels as a multiple of the local upper reference limit (Tn/URL). Secondary endpoints included periprocedural change in haemoglobin adjusted for red cells transfused, TIMI (Thrombolysis in Myocardial Infarction) bleeding, ST-segment recovery and infarct size determined by the Selvester QRS score.ResultsThe trial was terminated due to slow recruitment and futility after an interim analysis of 83 patients. The primary safety endpoint occurred in 6 (14%) patients in the bivalirudin group (4.8% GPIs) and 3 (7.3%) in the heparin ± GPIs group (54% GPIs) (risk ratio, 1.95, 95% confidence interval [CI], 0.52–7.3, P = 0.48). Infarct size was similar between the two groups (mean Tn/URL, 730 [±675] for bivalirudin, versus 984 [±1585] for heparin ± GPIs, difference, 254, 95% CI, -283-794, P = 0.86). There was a smaller decrease in the periprocedural haemoglobin level with bivalirudin than heparin ± GPIs (-7.5% [±15] versus -14% [±17], difference, -6.5%, 95% CI, -0.83–14, P = 0.0067). The rate of complete (≥70%) ST-segment recovery post-PCI was higher in patients randomised to heparin ± GPIs compared with bivalirudin.ConclusionsWhether bivalirudin compared with heparin ± GPI reduces bleeding in rescue PCI could not be determined. Slow recruitment and futility in the context of lower-than-expected bleeding event rates led to the termination of this trial (ANZCTR.org.au, ACTRN12610000152022).

Intracoronary pharmacological therapy versus aspiration thrombectomy in patients presenting with ST-segment elevation myocardial infarction (IPAT-STEMI): a systematic review and meta-analysis

Abstract Background Large thrombus load remains a challenge in the interventional cardiology practice. It precludes direct stent implementation and aggravates coronary obstruction leading to impaired myocardial perfusion, worsened cardiac function, and adverse clinical outcomes. Thus, various strategies have been advocated such as aspiration thrombectomy (AT), and/or localized or intracoronary (IC) treatment with thrombolytic agents and/or glycoprotein IIb/IIIa inhibitors (GPI). Purpose To evaluate the effectiveness of IC-administered pharmacological agents alone or combined with AT compared with AT alone as an adjunct to percutaneous coronary intervention (PCI) in STEMI patients with large thrombus burden. Methods The method was conducted according to the Cochrane Handbook for Systematic Reviews and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. A systematic search strategy using MEDLINE, EMBASE, CENTRALE, Scopus, ProQuest Public Health, Web of Science databases was performed on February 22, 2020 and updated on February 13, 2021. Eligible trials were randomized controlled trials (RCT) comparing IC-administered thrombolytic agents and/or GPI with or without AT to AT alone in patients presenting with STEMI who underwent PCI. The primary outcomes included coronary reperfusion indices e.g., thrombolysis in myocardial infarction (TIMI) flow grade 3 (G3), TIMI myocardial perfusion grade (TMPG) 3, Myocardial blush grade (MBG) 2/3, ST-segment resolution (STR). Others included clinical outcomes e.g., major adverse cardiovascular events (MACE). Results Twelve RCT enrolled 1,466 patients were included in the final analysis. The trials were categorized into 3 groups: (1) Thrombolytics [4 RCT], (2) GPI [3 RCT], and (3) GPI+AT [7 RCT]. Groups 2 and 3 included two mutual studies with multiple arms. In comparison with AT alone, thrombolytic therapy, as presented in four RCT, significantly improved TIMI flow G3 (OR = 3.71, 95% CI: 1.85–7.45; P overall effect = 0.0002; heterogeneity = 0%), complete STR (OR = 3.64, 95% CI: 1.60–8.26; P overall effect = 0.002; heterogeneity = 34%) and MACE (OR = 0.47, 95% CI: 0.22–0.99; P overall effect = 0.05; heterogeneity = 46%), but not TMPG 3. Pooling the data of the two studies with similar intervention i.e., thrombolytics + AT further refined the results with statistical improvement of TMPG 3 as well (OR = 5.44, 95% CI: 2.61- 11.34; P overall effect <0.ehab724.211201; heterogeneity = 0%) (Fig. 1). Pooled results for GPI and GPI+AT groups did not show statistical improvement in TIMI flow G3, MBG 2/3, nor complete STR (Fig. 2). Conclusion The findings of this meta-analysis showed that IC-administered thrombolytic agents improved myocardial reperfusion and MACE compared with AT alone in STEMI patients undergoing PCI. Funding Acknowledgement Type of funding sources: None.

Safety and efficacy of bivalirudin in diabetic acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI)

Abstract Background Prevention of hemorrhagic complications has emerged as a priority in patients undergoing Percutaneous Coronary Intervention (PCI) in addition to suppressing thrombotic complications. This goal is challenging to achieve in diabetic Acute Coronary Syndrome (ACS) patients as Diabetes Mellitus (DM) itself is a prothrombotic state with more pronounced vascular injury response and have a worse outcome after PCI compared with non-diabetic patients. In patients with ACS, Bivalirudin has been shown to result in similar rates of composite ischemia as Heparin plus GPI (GP IIb /IIIa inhibitor), while significantly reducing major bleeding and has received class I recommendation for PCI by American College of Cardiology (ACC 2013). Whether Bivalirudin is safe and effective specially in diabetic ACS patients undergoing PCI, as compared with Heparin (UFH) monotherapy, is unknown. Purpose To determine and compare the incidence of in-hospital and 30-day hemorrhagic complications and major adverse cardiac events (MACEs) as evidence of safety and efficacy using Bivalirudin versus Heparin in diabetic ACS patients undergoing PCI. Methods 218 diabetic ACS patients (age>18 years and ≤75 years) who underwent PCI from May 2018 to April 2019 at University Cardiac Centre, BSM Medical University, Dhaka, Bangladesh were randomly assigned to have UFH or Bivalirudin. Before the guide wire crossed the lesion, 111 patients in the UFH group received a bolus of 70–100 U/kg (targeted activated clotting time, ACT: 200–250 s). 107 patients in the Bivalirudin group received a loading dose of 0.75 mg/kg, followed by an infusion of 1.75 mg/kg/h for up to 4 hours. Dual antiplatelet (DAPT) loading as Aspirin 300 mg plus P2Y12 inhibitors (Clopidogrel 600 mg or Prasugrel 60 mg or Ticagrelor 180 mg) was given in all patients before the procedure. The maintenance dose of DAPT was continued for at least one month and patients were followed telephonically up to 30 days. The outcome measures were in-hospital and 30-day hemorrhagic complications and MACEs [death, MI, target vessel revascularization (TVR) and stroke]. Results Patients treated with Bivalirudin compared with Heparin had a significantly lower in-hospital incidence of QMI (0% vs. 6%; p=0.03) and major bleeding (0% vs. 7%; p=0.02). However, the incidence of cardiac death, stent thrombosis, TVR were no differences between two groups (p>0.05). There was only one NQMI in the Bivalirudin group as opposed to 8% in the Heparin group in 30 days following stenting (p=0.04). Conclusion In diabetic ACS patients undergoing PCI, Bivalirudin is safe and effective as it reduces immediate and short-term hemorrhagic complications as well as MACEs as compared with Heparin. Funding Acknowledgement Type of funding sources: None.

Vitamin D deficiency predicts the no-reflow phenomenon in STEMI patients undergoing primary percutaneous coronary intervention

Abstract Background Vitamin D displays a broad spectrum of cardioprotective effects, preventing oxidative stress, inflammation and thrombosis and improving endothelial function. Previous studies have associated vitamin D deficiency with more extended and severe coronary artery disease (CAD) and worse outcome, and especially among patients with ST-segment elevation myocardial infarction (STEMI). Few data have been reported on the association of vitamin D levels with the features of infarct-related lesions and PCI outcomes. Aim We aimed at assessing the relationship between vitamin D and angiographic findings and the procedural results of primary percutaneous coronary intervention (pPCI) in STEMI. Methods A consecutive cohort of patients admitted for STEMI treated with pPCI were included. The levels of 25(OH)D were assessed at admission by chemiluminescence immunoassay kit LIAISON® Vitamin D assay. Hypovitaminosis D was defined for 25(OH)D <10 ng/ml. Results We included in our study 450 patients, divided according to tertiles values of 25(OH)D. Lower vitamin D was associated to higher use of diuretics (p=0.02), higher levels of white blood cells and glycemia (p<0.001), lower prevalence of lesions on bifurcations (p=0.03) and smaller diameter of the target coronary vessel (p=0.03). Procedural characteristics and pre-procedural TIMI flow were not different according to vitamin D levels, but for a higher rate of slow-flow/no-reflow phenomenon (12.8% vs 8.1% vs 5.3%, p=0.03, adjusted OR [95% CI]=2.6 [1.05–6.6], p=0.04 for I vs III tertile), requiring higher use of adenosine (p=0.006) and glycoprotein IIbIIIa inhibitors (p=0.01). Conclusion The present study shows that among patients with STEMI undergoing pPCI, lower levels of vitamin D indepently predict the occurrence of slowflow/no-reflow phenomenon. Future dedicated studies will shed light on the prognostic implications of hypovitaminosis D in these patients and the potential therapeutic perspectives. Funding Acknowledgement Type of funding sources: None.

Effect of GP IIb/IIIa inhibitor duration on the clinical prognosis of primary percutaneous coronary intervention in ST-segment elevation myocardial infarction with no-/slow-reflow phenomenon

BackgroundIn patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) accompanied by the no-/slow-reflow phenomenon, the maintenance duration of GP IIb/IIIa inhibitor (GPI) is controversial. We compare the efficacy and safety of short- and long-term GPI infusion in STEMI patients with the no-/slow-reflow phenomenon. MethodsFrom June 2016 to December 2019, we continuously included patients with on-set STEMI who underwent pPCI, accompanied by the no-/slow-reflow, during interventional procedures at Guangdong Provincial People’s Hospital and Zhuhai Golden Bay Hospital. The hemorrhage events, heart function, and major adverse cardiovascular events (MACE) were compared between < 24 h and ≥ 24 h GPI duration groups. The Kaplan–Meier curve was used to estimate the 1-year MACE-free survival at different GPI utility times. ResultsIn total, 127 patients were divided into two groups based on the duration of tirofiban use (less and more than 24 h). There was no significant difference between two groups in terms of baseline characteristics, plaque condition, and coronary physiological function. The two groups showed similar in-hospital MACE (1 [1.85%] vs. 4 [5.48%], p = 0.394) and 1-year MACE-free survival (log-rank test p = 0.9085). The 1-year MACE remained consistent between the two groups in all subgroups of different risk factors of no-/slow-reflow. There was no significant difference in heart function and in-hospital hemorrhage events (3.7% vs. 1.37%, p = 0.179). ConclusionIn the real world, prolonging the duration of GPI may not significantly improve the clinical outcome in patients with STEMI with no-/slow-reflow.

The safety of the use of GP IIB/IIIA inhibitors with different types of dual antiplatelet therapy (DAPT)

Background and Aims: The risk and benefit of Glycoprotein IIb/IIIa inhibitors (GPI) use in combination with dual anti-platelet therapy (DAPT) especially the newer oral P2Y12 inhibitors in ST-Elevation Myocardial Infarction (STEMI) remain unassessed.