Glycoprotein IIb/IIIa Inhibitors Research Articles

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

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 multi-centre 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 (MI) and non-fatal stroke at one year. Secondary endpoints were defined as any bleeding events, 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 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. In patients with ACS undergoing PCI 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.

Glycoprotein inhibitors as a first line rescue treatment after unsuccessful recanalization of endovascular thrombectomy: A systematic review and meta-analysis.

Intracranial atherosclerotic disease (ICAD) is a major cause of stroke with a high rate of re-occlusion following mechanical thrombectomy (MT). Among the available rescue options, glycoprotein IIb/IIIa inhibitors (GPI) have shown promise as a potential therapeutic strategy. This systematic review and meta-analysis examine studies exploring the use of glycoprotein inhibitors as a first-line treatment for refractory occlusion or high-grade stenosis following EVT in the setting of ICAD. A systematic review and meta-analysis were performed. Studies using GPI as the first-line rescue treatment (GPI-rt) after failed thrombectomy or in the setting with high-grade stenosis (>50%) were included. The primary outcome of interest was good clinical outcomes (defined as a modified Rankin Scale (mRS) score of 0-2 at 90 days). Secondary outcomes of interest were successful recanalization (TICI 2b-3), symptomatic intracranial hemorrhage (sICH), and mortality by 90 days. Our study processed 2111 articles, which yielded eight relevant studies for review, four single and four double arm. These studies comprised 763 patients, divided into GPI-rt (535 patients) and non-GPI-rt (228 patients) cohorts. The GPI-rt group had higher rates of mRS ≤ 2 at 90 days (58.5% vs 38.9%, p = 0.002) and lower mortality rates (7.8% vs 17.5%, p = 0.04) compared to the non-GPI-rt cohort. mTICI 2b-3 rates and rates of sICH were not significantly different between the cohorts. First line GPI-rt demonstrates significant clinical benefit and significantly lower mortality without a rise in rates of sICH. GPI are a potential first line rescue treatment of ICAD.

Derivation and validation of the incomplete ST-segment resolution score and its usefulness for treatment with glycoprotein IIb-IIIa inhibitors.

Derivation and validation of the incomplete ST-segment resolution score and its usefulness for treatment with glycoprotein IIb-IIIa inhibitors.

Current use of antiplatelet therapy in the management of acute myocardial infarction: overview of the FRENCHIE national registry

Abstract Background There are many options for antiplatelet therapy (APT) at various stages in the management of acute myocardial infarction (MI) but few contemporary data regarding use in routine clinical practice in unselected patients. Purpose to describe the contemporary use of APT treatments in unselected MI patients. Methods FRENCHIE (FRENch CoHort of myocardial Infarction Evaluation) is a multicenter observational study (38 centers in France) consecutively enrolling patients with spontaneous MI whose symptoms were &amp;lt; 48 hours. Exclusion criteria were age &amp;lt; 18 years, no health coverage, unstable angina and procedure-related MI. Results Between September 2019 and December 2020, 10190 patients with MI were enrolled. Complete data on APT use were available for 9842 patients. Of these, 54.5% had ST elevation myocardial infarction (STEMI) and 45.5% non-STEMI (NSTEMI). During the first 24 hours, APT use for STEMI and NSTEMI patients, was as follows, respectively: acetylsalicylic acid (ASA) 95.1% and 88.8%, clopidogrel 12.4% and 17.7%, ticagrelor 79.5% and 55.0%, prasugrel 4.8% and 3.6%, GPIIb-IIIa inhibitors 23.8% and 6.5%, Cangrelor 1.1% and 0.8%. Among STEMI patients, 3.2% had undergone thrombolysis, 92.2% primary percutaneous coronary intervention (pPCI) and 4.5% did not have reperfusion during acute phase management. The use of ASA was similar regardless of the initial reperfusion strategy, but that of P2Y12 inhibitors (P2Y12i) was different. Clopidogrel was mainly used in case of thrombolysis, 69.6% of cases, while ticagrelor was mainly used in case of pPCI or medical treatment alone, respectively in 83.9% and 59.7% of cases. GPIIb-IIIa inhibitors were used in 9.3%, 26.2% and 11.4% in patients who had undergone thrombolysis, pCI and medical treatment respectively. At hospital discharge, APT use was as follows, respectively for STEMI and NSTEMI patients: ASA 94.6% and 91.2%, clopidogrel 14.7% and 21.8%, ticagrelor 72.6% and 54.9%, prasugrel 6.9% and 5.7%. The first P2Y12i administered was different from that retained at discharge in 15.4% of STEMI and 12.5% of NSTEMI patients. The most common scenario was switching from ticagrelor to clopidogrel in 64.2% of STEMI patients and 57.2% of NSTEMI patients. No P2Y12i was prescribed at discharge in 3.6% of STEMI patients and 11.3% of NSTEMI patients. Conclusion In contemporary practice in France, P2Y12i use was different according to MI type and to initial reperfusion strategy. GPIIb-IIIa inhibitors were used in more than a quarter of STEMI patients with pPCI. Switching between P2Y12i occurred in 1/8 of patients before discharge and deserves further investigation.

Impact of age on pre-procedural TIMI flow in STEMI patients undergoing primary percutaneous coronary intervention.

Advanced age is a major determinant of impaired prognosis among patients with ST-segment elevation myocardial infarction (STEMI). However, the mechanisms associated with suboptimal reperfusion and enhanced complications are still largely undefined. The aim of the present study was to assess the impact of age on the angiographic findings and the procedural results of primary percutaneous coronary intervention (pPCI) in patients with STEMI. A consecutive cohort of patients admitted for STEMI treated with pPCI were included. Infarct-related artery (IRA) patency was defined for preprocedural TIMI flow 3. We included 520 patients, divided according to age tertiles (<61; 61-72; ≥73). Elderly patients were more often females, with hypertension, renal failure, prior myocardial infarction or PCI, with lower rates of smoking history, haemoglobin, leukocytes and cholesterol (P < 0.001), lower ejection fraction (P = 0.02), higher use of renin angiotensin system inhibitors, statins, ASA, calcium antagonists, diuretics and beta blockers. At angiography, for the IRA, percentage of thrombus (P = 0.02) and stenosis (P = 0.01), direct stenting (P = 0.02) and glycoprotein IIb-IIIa inhibitors (P = 0.04) inversely related with age, but for higher restenosis (P = 0.04). IRA patency was more common in patients aged ≥73 years (27.9% vs. 32.3% vs. 41.1%, P = 0.01). The impact of age on preprocedural TIMI flow was confirmed at multivariate analysis [adjusted odds ratio (95% confidence interval) = 0.68 (0.47-0.98), P = 0.04]. The present study shows that among STEMI patients undergoing primary PCI, more advanced age represents an independent predictor of preprocedural IRA patency. Future studies will define the implications on procedural results and long-term prognosis.

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.

Intracoronary versus intravenous glycoprotein IIb/IIIa inhibitors during primary percutaneous coronary intervention in patients with STEMI: a systematic review and meta-analysis

BackgroundIntracoronary (IC) administration of glycoprotein IIb/IIIa inhibitors (GPIs) has been studied as an adjunctive therapy to improve outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of IC administration of GPIs compared with those of intravenous (IV) administration in patients with STEMI.MethodsWe searched the MEDLINE, Embase, and Cochrane CENTRAL databases for relevant studies published before September 21, 2022. In total, 22 randomized controlled trials involving 7,699 patients were included.ResultsThe proportions of patients achieving thrombolysis in myocardial infarction grade 3 flow, myocardial blush grade 2/3, and complete ST-segment resolution were significantly higher in the IC group than in the IV group. Major adverse cardiac events (MACE) (RR: 0.54, 95% CI: 0.37–0.80) and heart failure (RR: 0.48, 95% CI: 0.25–0.91) within 1 month were significantly lower in the IC group than in the IV group; however, after 6 months, no difference was observed in MACE risk. Additionally, the risks of death and bleeding did not differ between the two routes of administration.ConclusionsWhen considering adjunctive GPI administration for patients with STEMI, the IC route may offer greater benefits than the IV route in terms of myocardial reperfusion and reduced occurrence of MACE and heart failure within 1 month. Nonetheless, when making decisions for IC administration of GPIs, the absence of a benefit for bleeding risk and difficulty accessing the administration route should be considered.

Antithrombotic regimen in emergent carotid stenting for acute ischemic stroke due to tandem occlusion: a meta-analysis of aggregate data

BackgroundThe periprocedural antithrombotic regimen might affect the risk-benefit profile of emergent carotid artery stenting (eCAS) in patients with acute ischemic stroke (AIS) due to tandem lesions, especially after intravenous thrombolysis....

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.

Prepercutaneous coronary intervention Zalunfiban dose-response relationship to target vessel blood flow at initial angiogram in st-elevation myocardial infarction – A post hoc analysis of the cel-02 phase IIa study

Zalunfiban (RUC-4) is a novel, subcutaneously administered glycoprotein IIb/IIIa inhibitor (GPI) designed for prehospital treatment to initiate reperfusion in the infarct-related artery (IRA) before primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction (STEMI). Since GPIs have been reported to rapidly reperfuse IRAs, we assessed whether there was a dose-dependent relationship between zalunfiban treatment and angiographic reperfusion indices and thrombus grade of the IRA at initial angiogram in patients with STEMI. This was a post hoc analysis from the open-label Phase IIa study that investigated the pharmacodynamics, pharmacokinetics, and tolerability of three doses of zalunfiban - 0.075, 0.090 and 0.110 mg/kg - in STEMI patients. This analysis explored dose-dependent associations between zalunfiban and three angiographic indices of the IRA, namely coronary and myocardial blood flow and thrombus burden. Zalunfiban was administered in the cardiac catheterization laboratory prior to vascular access, ∼10 to 15 minutes before the initial angiogram. All angiographic data were analyzed by a blinded, independent, core laboratory. Twentyfour out of 27 STEMI patients were evaluable for angiographic analysis (0.075 mg/kg [n=7], 0.090 mg/kg [n=9], and 0.110 mg/kg [n=8]). TIMI flow grade 2 or 3 was seen in 1/7 patients receiving zalunfiban at 0.075 mg/kg, in 6/9 patients receiving 0.090 mg/kg, and in 7/8 patients receiving 0.110 mg/kg (ptrend=0.004). A similar trend was observed based on TIMI flow grade 3. Myocardial perfusion was also related to zalunfiban dose (ptrend=0.005) as reflected by more frequent TIMI myocardial perfusion grade 3. Consistent with the dose-dependent trends in greater coronary and myocardial perfusion, TIMI thrombus ≥4 grade was inversely related to zalunfiban dose (ptrend=0.02). This post hoc analysis found that higher doses of zalunfiban administered in the cardiac catheterization lab prior to vascular access were associated with greater coronary and myocardial perfusion, and lower thrombus burden at initial angiogram in patients with STEMI undergoing primary percutaneous coronary intervention.

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.

Contemporary approach to thrombus containing lesions during primary percutaneous coronary interventions in ST-segment elevation myocardial infarction (from the ORPKI National Registry in Poland)

Abstract Background In the era of potent P2Y12 inhibitors, according to current guidelines on ST-segment elevation myocardial infarction (STEMI), treatment with glycoprotein IIb/IIIa inhibitors (GPI) should be limited to selected bail-out or highly thrombotic situations. Similarly, aspiration thrombectomy (AT) is downgraded in current guidelines for very selective but not routine usage. Both recommendations make the treatment of thrombus containing lesions somewhat defensive, underlining the need for an individualized approach to STEMI patients. However, data concerning current clinical practice of such approach are limited. Purpose We examined the prevalence, procedural characteristics, and predictors of GPI administration and AT usage in all-comers contemporary STEMI patients referred to primary PCI in Poland. Methods We focused on 116,873 consecutive STEMI patients undergoing primary PCI in Poland between 2015 and 2020. Results GPIs were administered in 29.3% of patients and AT was used in 11.6%, with combined treatment with GPI and AT in 6.1% of patients. There was a slight trend towards a decrease in GPI and AT usage during the analyzed years. On the opposite, there was a rapid growth of the ticagrelor/prasugrel usage rate from 6.5% in 2015 to 48.1% in 2020 (Figure 1). Patients with periprocedural GPI administration and combined strategy with GPI and AT were younger, more often men, with history of smoking and presented with cardiogenic shock on admission. They were less likely to have diabetes, chronic kidney disease and previous stroke. Occluded infarct-related artery in baseline angiography and no-reflow during PCI were the strongest independent predictors of GPI administration and combined usage of GPI and AT in a multivariate logistic regression model. Similarly, administration of ticagrelor/prasugrel was an independent predictor of both adjunctive treatment strategies (see table for details). Conclusions Despite the rapid growth of potent P2Y12 inhibitors usage in Poland in recent years, GPI and AT are selectively used at a stable level during primary PCI in highly thrombotic STEMI lesions. Funding Acknowledgement Type of funding sources: None.

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).

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.