High-risk Acute Coronary Syndrome Patients Research Articles

Radial Artery Access for Acute Coronary Syndromes: a Review of Current Evidence.

To review the evidence supporting the use of transradial access (TRA) for percutaneous coronary intervention (PCI) in acute coronary syndromes (ACS). There have been five major randomized controlled trials (RCTs) and two recent meta-analyses comparing outcomes of TRA and femoral access (FA) in ACS. Additional studies have explored the impact of TRA on STEMI door-to-balloon (D2B) times, TRA in high-risk ACS patients, the potential conflict between TRA and coronary artery bypass graft (CABG) surgery employing the radial artery, and distal radial artery (DRA) access. TRA is associated with a reduction in net adverse clinical events, major bleeding, acute renal injury, and access site complications compared to FA in ACS patients undergoing PCI. TRA is not associated with significant delays in STEMI D2B times that impact patient outcomes. Further studies are needed to evaluate the role of TRA in high-risk ACS patients, the interplay between TRA and radial artery CABG, and use of DRA in ACS.

Early and late recurrent cardiovascular events among high-risk patients with an acute coronary syndrome: Meta-analysis of phase III studies and implications on trial design.

BackgroundDespite low‐density lipoprotein cholesterol‐lowering therapies and other standard‐of‐care therapy, there remains a substantial residual atherosclerotic risk among patients with an acute coronary syndrome (ACS). This study aims to estimate the risk of early and late recurrent major adverse cardiovascular events (MACE) and address its implications on trial design.MethodsA literature search was performed to collect phase III interventional trials on high‐risk ACS patients. Pooled event rates at 90 and 360 days were estimated by fitting random‐effects models using the DerSimonian–Laird method. Under the assumption of a total sample size of 10,000 and 1:1 allocation at a one‐sided alpha of 0.025 using the log‐rank test, the relationship between power and relative risk reduction (RRR) or absolute risk reduction (ARR) was explored for early versus late MACE endpoint.ResultsSeven trials representing 82,727 recent ACS patients were analyzed. The pooled rates of recurrent MACE were 4.1% and 8.3% at 90 and 360 days. Approximately 49% of events occurred within the first 90 days. Based on the estimated risks at 90 and 360 days, to attain 90% statistical power, a lower magnitude of RRR is required for late MACE than early MACE (22% vs. 30%), whereas a lower magnitude of ARR is required for early MACE than late MACE (1.2% vs. 1.8%).ConclusionThe initial 90‐day window after ACS represents a vulnerable period for recurrent events. From a trial design perspective, determining a clinically important benefit by RRR versus ARR may influence the decision between early and late MACE as the study endpoint.

Early and Late Recurrent Cardiovascular Risk in Patients With Recent Acute Coronary Syndrome: Meta-Analysis and Implications in Trial Design†

Lead Author's Financial Disclosures G.C. has receieved research grant support to the Beth Israel Deaconess Medical Center, Harvard Medical School from Portola Pharmaceuticals, Bayer, Janssen Scientific Affairs, and CSL Beh-ring. Study Funding CSL Behring. Background/Synopsis Despite optimal medical therapy, a substantial residual atherosclerotic risk exists among patients with an acute coronary syndrome (ACS). Objective/Purpose This study aimed to estimate the risk of early and late major adverse cardiovascular events (MACE) and address its implications in trial design. Methods A comprehensive search was performed to collect phase III interventional trials on high-risk ACS patients. Pooled event rates at 90 and 360 days were estimated with meta-analytic approaches by fitting a random-effects model using the DerSimonian-Laird method. Using the log-rank test (n=10,000; 1-sided α=0.025)), the relationship between power and relative risk reduction (RRR) or absolute risk reduction (ARR) was explored for early vs. late MACE endpoint. Results A total of 82,727 high-risk patients with recent ACS from 7 trials were analyzed. Pooled rates of recurrent MACE were 4.1% (95% CI: 3.0% to 5.7%) at 90 days and 8.3% (95% CI: 7.1% to 9.8%) at 360 days. Approximately 49% of events occurred within the first 90 days. To attain 90% statistical power, a lower RRR is required for late MACE (22% vs. 30%), whereas a lower ARR is required for early MACE (1.2% vs. 1.8%). Conclusions The initial 90-day window after an ACS event represents a vulnerable period for recurrent MACE. From a trial design perspective, determining a clinically important benefit by relative vs. absolute risk reduction may influence the choice between early vs. late MACE as the study endpoint. G.C. has receieved research grant support to the Beth Israel Deaconess Medical Center, Harvard Medical School from Portola Pharmaceuticals, Bayer, Janssen Scientific Affairs, and CSL Beh-ring.

Study of pattern & distribution of adverse drug reactions in acute coronary syndrome patients in a tertiary care hospital

With the availability of a wide range of drugs to treat patients with acute coronary syndrome (ACS), adverse drug reactions (ADRs) have become inevitable in clinical practice. Thorough knowledge of such reactions is essential for the treating physician for optimal treatment and better outcomes. There are many scales to define, measure and assess the ADRs, but there is a dearth of data available on such drug reactions among ACS patients. Hence, this study attempted to analyze the pattern, causality, severity, predictability and preventability of ADRs in ACS patients. All the ADRs reported during the study period were analyzed for causality by the World Health Organization-Uppsala Monitoring Centre (WHO-UMC), Naranjo's and Karch and Lasagna scales; severity by modified Hartwig and Siegel scale; predictability by Rawlins and Thompson criterion and preventability by Schumock and Thornton scale. A single-centre, record-based analysis for the occurrence of ADRs was done among ACS patients admitted to the department of Cardiology between January and October 2017. Demographic data, comorbid conditions, reported ADRs and ADR assessment details were noted from the hospital case records and ADR monitoring centre (AMC) records. The data were analyzed and presented in a descriptive manner using percentages, mean and standard deviation. The Pearson's chi-squared test was used to ascertain the significance of the association between different groups. Out of 324 patients under evaluation, 67 had developed one or more ADRs. There were 30 different types of ADRs reported, headache being the most common. Among the drugs, heparin was the most common factor, causing 27 per cent of ADRs. Definite causality of a suspected drug causing ADRs was seen in 11.9 (n=8), nine (n=6) and 7.5 (n=5) per cent cases as per WHO-UMC, Naranjo (Naranjo algorithm) and Karch and Lasagna scales, respectively. In the severity of ADRs, the most severe reactions according to the modified Hartwig-Siegel scale (level 4a in our study) were seen in 17.5 (n=12) per cent of patients, and the rest were either level 2 or 3 reactions. Nearly 92.5 (n=62) per cent of reactions were predictable according to the Rawlins and Thompson criterion. Application of the modified Schumock-Thornton scale showed that 22.4 per cent of ACS patients had preventable reactions, and the rest were not preventable. The study results suggest that ADRs are relatively common among ACS patients. Most of these can be identified and assessed for causality, severity, predictability and preventability using various available scales. Diligent pharmacovigilance for identifying and assessing ADRs may help manage and mitigate morbidity associated with these in high-risk ACS patients.

Apixaban versus PhenpRocoumon: Oral AntiCoagulation plus antiplatelet tHerapy in patients with Acute Coronary Syndrome and Atrial Fibrillation (APPROACH-ACS-AF): Rationale and design of the prospective randomized parallel-group, open-label, blinded-endpoint, superiority, multicenter-trial of a triple therapy versus a dual therapy in patients with Atrial Fibrillation and Acute Coronary Syndrome undergoing coronary stenting.

BackgroundA regimen of dual (DAT) vs. triple (TAT) antithrombotic therapy reduces bleeding in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). However, recent evidence suggests that DAT may be associated with an increased ischemic risk. This raises the question whether DAT rather than TAT should be recommended to AF patients that undergo PCI for acute coronary syndrome (ACS), carrying a particularly high risk of both bleeding and ischemic events, studied only as subgroups of previous trials.Methods and designThe APPROACH-ACS-AF-(DZHK-7) trial is a multicenter prospective, randomized, open-label, blinded endpoint (PROBE) trial which will include patients presenting with an ACS managed by PCI and requiring oral anticoagulation (OAC) due to AF. The trial will test, whether a DAT-regimen comprising clopidogrel plus the non-Vitamin-K-antagonist oral anticoagulant (NOAC) apixaban is superior to a TAT-regimen of vitamin-K-antagonist (VKA) plus dual anti-platelet therapy (APT) with respect to bleeding. A total of 400 patients will be randomized 1:1 to a control-arm with guideline-recommended TAT with VKA plus clopidogrel and acetylsalicylic-acid and a study arm receiving DAT comprising apixaban plus clopidogrel. Patients will be followed-up for 6 months. The primary endpoint of the study is the cumulative incidence of BARC type ≥2 bleeding, secondary endpoints include a composite clinical ischemic outcome and net clinical outcome.ConclusionsAPPROACH-ACS-AF is the first trial dedicated to ACS patients, testing whether in terms of bleeding a DAT with NOAC is superior to a TAT regimen with VKA in high-risk ACS patients with AF.

Hospital in the air: Royal Flying Doctor Service retrievals and challenges before, during and after, Australia's COVID‐19 lockdown in 2020

Hospital in the air: Royal Flying Doctor Service retrievals and challenges before, during and after, Australia's <scp>COVID</scp>‐19 lockdown in 2020

Antithrombotic therapy in patients with acute coronary syndrome complicated by cardiogenic shock or out-of-hospital cardiac arrest: a joint position paper from the European Society of Cardiology (ESC) Working Group on Thrombosis, in association with the Acute Cardiovascular Care Association (ACCA) and European Association of Percutaneous Cardiovascular Interventions (EAPCI).

Timely and effective antithrombotic therapy is critical to improving outcome, including survival, in patients with acute coronary syndrome (ACS). Achieving effective platelet inhibition and anticoagulation, with minimal risk, is particularly important in high-risk ACS patients, especially those with cardiogenic shock (CS) or those successfully resuscitated following out-of-hospital cardiac arrest (OHCA), who have a 30-50% risk of death or a recurrent ischaemic event over the subsequent 30 days. There are unique challenges to achieving effective and safe antithrombotic treatment in this cohort of patients that are not encountered in most other ACS patients. This position paper focuses on patients presenting with CS or immediately post-OHCA, of presumed ischaemic aetiology, and examines issues related to thrombosis and bleeding risk. Both the physical and pharmacological impacts of CS, namely impaired drug absorption, metabolism, altered distribution and/or excretion, associated multiorgan failure, co-morbidities and co-administered treatments such as opiates, targeted temperature management, renal replacement therapy and circulatory or left ventricular assist devices, can have major impact on the effectiveness and safety of antithrombotic drugs. Careful attention to the choice of antithrombotic agent(s), route of administration, drug-drug interactions, therapeutic drug monitoring and factors that affect drug efficacy and safety, may reduce the risk of sub- or supra-therapeutic dosing and associated adverse events. This paper provides expert opinion, based on best available evidence, and consensus statements on optimising antithrombotic therapy in these very high-risk patients, in whom minimising the risk of thrombosis and bleeding is critical to improving outcome.

Impact of total occlusion of culprit artery in acute non-ST elevation myocardial infarction: a systematic review and meta-analysis.

Total occlusion (TO) of the culprit artery usually presents with ST-elevation myocardial infarction. A subset of patients with TO present as non-ST segment elevation myocardial infarction (NSTEMI) without classic ST-elevation on the electrocardiogram. This may lead to delay in identification of these patients and further management. We performed a meta-analysis to estimate the difference in outcomes between totally occluded and non-occluded culprit arteries in patients with NSTEMI. Our literature search yielded seven studies with 40 777 patients. The outcomes assessed were clinical presentation (Killip class), left ventricular ejection fraction, time to angiography, major cardiac adverse events (MACE) and all-cause mortality. The generic inverse or Mantel-Haenszel method was used to pool relevant outcomes and the mean difference (MD) or relative risk (RR) was calculated. A total of 10 415 (25.5%) patients had an occluded culprit artery with a predominant infero-lateral distribution (40% right coronary and 33% left circumflex artery). There was an increased risk of both MACE (short-term RR: 1.41; CI: 1.17, 1.70; P = 0.0003; I2 = 26%; medium- to long-term RR: 1.32; CI: 1.11, 1.56; P = 0.001; I2 = 25%) and all-cause mortality (short-term RR: 1.67; CI: 1.31, 2.13; P < 0.0001; I2 = 41%; medium to long-term RR: 1.42; CI: 1.08, 1.86; P = 0.01; I2 = 32%) with TO of the culprit artery. Our meta-analysis suggests that patients with NSTEMI who demonstrate a totally occluded culprit vessel on coronary angiography are at higher risk of mortality and major adverse cardiac events. Better risk stratification tools are needed to identify such high-risk acute coronary syndrome patients to facilitate earlier revascularization and potentially to improve outcomes.

Usefulness of the residual SYNTAX score to predict long term outcome in acute coronary syndrome patients underwent percutaneous coronary intervention

Objective: To quantify the extent and complexity of residual coronary stenosis following PCI by the residual SYNTAX score, and to evaluate its impact on adverse ischemic outcomes in acute coronary syndrome(ACS) patients. Methods: From January 2013 to December 2013, a total of 1 414 consecutive moderate- and high-risk ACS patients who underwent any PCI with multi-vessel coronary artery disease were evaluated.Patients were stratified by rSS quartiles and their outcomes were compared. Results: The rSS was 4.8±6.7. 591 patients (41.8%) had rSS=0(CR), 233 patients (16.5%) had rSS>0 but ≤ 3, 296 patients (20.9%) had rSS>3 but ≤8 and 294 patients (20.8%) had rSS>8.Clinical risk factors were more frequent in patients with incomplete revascularization(IR) compared with complete revascularization(CR). The 2-year rates of all-caused death(1.2% vs 0.4%, 2.0%, 4.4%, P=0.003), cardiac death, revascularization and MACCE were significantly higher in high rSS group, compared to other groups.By multivariable analysis, rSS was a strong independent predictor of ischemic outcomes at 2-year, including all-cause mortality (HR=1.05, 95%CI 1.01-1.09, P=0.019), cardiac death, revascularization and MACCE. Conclusions: The rSS is a strong independent predictor of all-caused death, cardiac death, revascularization and MACCE and has moderated predictive ability for those ischemic outcomes.

Evidence-based care in a population with chronic kidney disease and acute coronary syndrome. Findings from the Australian Cooperative National Registry of Acute Coronary Care, Guideline Adherence and Clinical Events (CONCORDANCE)

Acute coronary syndrome (ACS) guidelines recommend that patients with chronic kidney disease (CKD) be offered the same therapies as other high-risk ACS patients with normal renal function. Our objective was to describe the gaps in evidence-based care offered to patients with ACS and concomitant CKD. Patients presenting to 41 Australian hospitals with suspected ACS were stratified by presence of CKD (glomerular filtration rate <60 mL/min). Receipt of evidence-based care including, coronary angiography (CA), evidence-based discharge medications (EBMs), and cardiac rehabilitation (CR) referral, were compared between patients with and without CKD. Hospital and clinical factors that predicted receipt of care were determined using multilevel multivariable stepwise logistic regression models. Of the 4,778 patients admitted with suspected ACS, 1,227 had CKD. On univariate analyses, patients with CKD were less likely to undergo CA (59.1% vs 85.0%, P < .0001) or receive EBM (69.4% vs 78.7%, P < .0001), or were offered CR (49.5% vs 68.0%, P < .0001). After adjusting for patient characteristics and clustering by hospital, CKD remained an independent predictor of not undergoing CA only (odds ratio 0.48, 95% CI 0.37-0.61). Within the CKD cohort, presenting to a hospital with a catheterization laboratory was the strongest predictor of undergoing CA (odds ratio 3.07, 95% CI 1.91-4.93). The presence of CKD independently predicts failure to undergo CA but not failure to receive EBM or CR, which is predicted by comorbidities. Among the CKD population, performance of CA is largely determined by admission to a catheterization capable hospital. Targeting these patients through standardization of care across institutions offers opportunities to improve outcomes in this high-risk population.

Echocardiographic parameters as predictors of in-hospital mortality in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

Different ways have been used to stratify risk in acute coronary syndrome (ACS) patients. The aim of the study was to examine the usefulness of echocardiographic parameters as predictors of in-hospital outcome in patients with ACS after percutaneous coronary intervention (PCI). A data of 2030 patients with diagnosis of ACS hospitalized from December 2008 to December 2011 was used to develop a risk model based on echocardiographic parameters using the binary logistic regression. This model was independently evaluated in validation cohort prospectively (954 patients admitted during 2012). In-hospital mortality in derivation cohort was 7.73%, and 6.28% in validation cohort. Developed model has been designed with 4 independent echocardiographic predictors of in-hospital mortality: left ventricular ejection fraction (LVEF RR = 0.892; 95%CI = 0.854–0.932, P < 0.0005), aortic leaflet separation diameter (AOvs RR = 0.131; 95%CI = 0.027–0.627, P = 0.011), right ventricle diameter (RV RR = 2.675; 95%CI = 1.109–6.448, P = 0.028) and right ventricle systolic pressure (RVSP RR = 1.036; 95%CI = 1.000–1.074, P = 0.048). Model has good prognostic accuracy (AUROC = 0.84) and it retains good (AUROC = 0.78) when testing on the validation cohort. Risks for in-hospital mortality after PCI in ACS patients using echocardiographic measurements could be accurately predicted in contemporary practice. Incorporation of such developed model should facilitate research, clinical decisions, and optimizing treatment strategy in selected high risk ACS patients.

Platelet Inhibition by Abciximab Bolus-Only Administration and Oral ADP Receptor Antagonist Loading in Acute Coronary Syndrome Patients: The Blocking and Bridging Strategy

IntroductionCurrent guidelines still recommend the bolus and infusion administration of glycoprotein IIbIIIa inhibitors in patients with high-risk acute coronary syndrome undergoing percutaneous coronary intervention. We sought to evaluate the extent of platelet inhibition by a blocking and bridging strategy with intracoronary abciximab bolus-only administration and oral loading of adenosine diphosphate receptor antagonists. Patients and methodsFifty-six consecutive high-risk acute coronary syndrome patients with bolus-only abciximab administration (0.25mg/kg i.c.) and loading with 600mg clopidogrel (55%) or 60mg prasugrel (45%) were included in this study. Platelet aggregation induced by thrombin receptor-activating peptide and adenosine diphosphate was measured by multiple electrode aggregometry up to 7days. ResultsThrombin receptor-activating peptide induced platelet aggregation was significantly suppressed for a minimum of 48h (45±17U) and returned to a normal range (>84U) after 6days (90±26U; p<0.001). Co-medication with prasugrel significantly reduced adenosine diphosphate-induced (p=0.002) and thrombin receptor-activating peptide-induced (p=0.02) platelet aggregation compared with clopidogrel throughout the observation period. No stent thrombosis or repeat myocardial infarction occurred at 30-day follow-up. ConclusionsImmediate blocking of platelet aggregation in high-risk acute coronary syndrome patients by intracoronary abciximab bolus-only administration and bridging to prolonged inhibition via oral blockade of ADP receptors effectively inhibited overall platelet reactivity for at least 48h, questioning the value of continuous abciximab infusion. Co-medication with prasugrel vs. clopidogrel synergistically augmented platelet inhibition.

Novel Antiplatelet Agents: ALX-0081, a Nanobody Directed towards von Willebrand Factor

This manuscript reviews the studies performed with ALX-0081 (INN: caplacizumab), a Nanobody targeting von Willebrand factor, in the context of current antithrombotic therapy in coronary artery disease. ALX-0081 specifically inhibits platelet adhesion to the vessel wall, and may control platelet aggregation and subsequent clot formation without increasing bleeding risk. A substantial number of antithrombotics are aimed at this cascade; however, their generally indiscriminative mode of action can result in a narrow therapeutic window, defined by the risk for bleeding complications, and thrombotic events. Nonclinically, ALX-0081 compared favorably to several antithrombotics. In Phase I studies in healthy subjects and stable angina patients undergoing percutaneous coronary intervention (PCI), ALX-0081 was well tolerated, and effectively inhibited pharmacodynamic markers. Following these results, a phase II study was initiated in high-risk acute coronary syndrome patients undergoing PCI. Based on its mechanism of action, ALX-0081 is also being developed for acquired thrombotic thrombocytopenic purpura.

Tirofiban versus abciximab: tirofiban is administered at suboptimal dosages when evaluated in an arterial thrombosis model in non-human primates

To prevent thrombosis in high-risk acute coronary syndrome patients undergoing percutaneous coronary intervention for re-vascularisation, concomitant administration of a glycoprotein IIb/IIIa inhibitor, such as abciximab, tirofiban or eptifibatide, is recommended. Abciximab and eptifibatide are mostly preferred over tirofiban, which is less effective in preventing ischaemic events. We compared the efficacy and bleeding potential of escalating doses of tirofiban and abciximab in non-human primates. The efficacy of tirofiban and abciximab in inhibiting cyclic flow reductions (CFRs) was tested in a high shear arterial thrombosis model. Bleeding was evaluated with the template bleeding time and an incision bleeding model. Abciximab completely inhibited arterial thrombosis after injection of its therapeutic bolus dose. With tirofiban, a dose three times higher than the recommended therapeutic dose caused weak inhibition characterised by a return of CFRs after re-injury. At nine times the recommended therapeutic dose, complete inhibition was observed, and the efficacy of tirofiban was comparable to abciximab at its therapeutic bolus dose. Blood loss was less than with abciximab at its effective dose. In this model, tirofiban compared favourably with abciximab, although only at a dose of 3-9 times the therapeutic dose, and caused less bleeding than abciximab.

Impact of Abciximab in Elderly Patients with High-Risk Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

An increasing proportion of patients with acute coronary syndrome (ACS) requiring percutaneous coronary intervention (PCI) are classified as elderly (aged ≥70 years). The glycoprotein IIb/IIIa inhibitor abciximab is known to reduce adverse outcomes in patients aged <70 years with high-risk ACS undergoing PCI, but conflicting findings relating to its effects in the elderly have been reported. The aim of this study was to evaluate the effect of abciximab in elderly high-risk ACS patients undergoing PCI. From our dedicated PCI registry we identified 2068 ACS patients with high-risk lesions that were treated with PCI. Baseline data were collected prospectively. All-cause mortality, target vessel revascularization (TVR), myocardial infarction (MI), and the combination of these were primary study endpoints. All endpoints within 1 year after PCI were registered and validated. The population was subsequently stratified according to age and use of abciximab. Elderly patients constituted 42% of the total population. They presented with more co-morbidities, were less frequently treated with abciximab and had a higher risk of reaching the combined endpoint and higher all-cause mortality than younger patients. The age/abciximab stratified analysis revealed no effect of abciximab on any of the endpoints in elderly patients (combined endpoint: no abciximab 22.6% vs abciximab 23.4%, p=0.85; all-cause mortality: no abciximab 15.4% vs abciximab 15.9%, p=0.91; TVR: no abciximab 3.4% vs abciximab 5.5%, p=0.21; MI: no abciximab 7.0% vs abciximab 8.5%, p=0.54), whereas all-cause mortality and the risk of reaching the combined endpoint were significantly reduced in younger patients (combined endpoint: no abciximab 14.0% vs abciximab 9.4%, p=0.03; all-cause mortality: no abciximab 4.5% vs abciximab 1.7%, p=0.02; TVR: no abciximab 5.5% vs abciximab 4.3%, p=0.39; MI: no abciximab 7.2% vs abciximab 6.6%, p=0.80). These findings were confirmed in our adjusted analyses. In this large observational study we found no benefit of abciximab treatment in elderly high-risk ACS patients who underwent PCI. These findings should be taken into consideration when deciding on the treatment strategy for elderly ACS patients undergoing PCI.

Abciximab as an adjunctive therapy for patients undergoing percutaneous coronary interventions

Introduction: Platelets play a central role in the pathophysiology of acute coronary syndromes (ACS) and activation of platelet glycoprotein (GP) IIb/IIIa receptor is critical to platelet aggregation. Abciximab, a human murine chimeric antibody to the GPIIb/IIIa receptor, is an important biological therapy in the management of patients presenting with ACS.Areas covered: The objective of this review is to define the role of abciximab in the management of ACS by interpreting the available data from randomized clinical trials using abciximab in various clinical scenarios, particularly in percutaneous coronary intervention (PCI). We also review different modes of delivery and describe the adverse effects of abciximab including thrombocytopenia. Where possible, we attempt to compare abciximab to the other available GPIIb/IIIa inhibitors. We hope the reader will gain a better understanding of the benefits and risks of abciximab and the important role it has in the management of cardiology patients.Expert opinion: Abciximab was a breakthrough drug in the management of high risk ACS patients undergoing PCI. However, with newer available therapies and improvement in PCI technology, dose and delivery of this drug have evolved as we try to extract maximum benefit while minimizing the adverse effects associated with it.

Meta-Analysis of Randomized Trials of Glycoprotein IIb/IIIa Inhibitors in High-Risk Acute Coronary Syndromes Patients Undergoing Invasive Strategy

It is still unknown whether upstream administration of glycoprotein (Gp) IIb/IIIa inhibitors, aiming at cooling the culprit lesion before angioplasty, is superior to its selective downstream administration in high-risk patients with acute coronary syndromes (ACSs) undergoing coronary angioplasty. Therefore, the aim of the present study was to perform a meta-analysis of randomized trials comparing upstream to downstream administration of Gp IIb/IIIa inhibitors in high-risk patients with ACS undergoing early invasive strategy. We obtained results from all randomized trials on this issue. The literature was scanned by formal searches of electronic databases from January 1990 to March 2010. The following key words were used: "randomized trial," "myocardial infarction," "ACS," "coronary angioplasty," "upstream," "downstream," "Gp IIb/IIIa inhibitors," "abciximab," "tirofiban," and "eptifibatide." Primary and secondary clinical end points were mortality and myocardial infarction at 30 days, respectively. Major bleeding complications were assessed as a safety end point. Seven randomized trials were included in the meta-analysis, involving 19,929 patients (9,981 or 50.0% in the upstream Gp IIb/IIIa inhibitors group and 9,948 or 50% in the downstream Gp IIb/IIIa inhibitors group). Upstream Gp IIb/IIIa inhibitors did not decrease 30-day mortality (2.0% vs 2.0%, p = 0.84) or recurrence of myocardial infarction (7.0% vs 7.6%, p = 0.11) but were associated with higher risk of major bleeding complications (1.8% vs 1.3%, p = 0.0002). In conclusion, this meta-analysis shows that in high-risk patients with ACS undergoing an early invasive strategy, upstream administration of Gp IIb/IIIa inhibitors does not improve clinical outcome compared to a downstream selective administration, and it is associated with an increased risk of major bleeding complications. Therefore, a strategy of upstream Gp IIb/IIIa inhibitors cannot be recommended.

Lipid-lowering intensification and low-density lipoprotein cholesterol achievement from hospital admission to 1-year follow-up after an acute coronary syndrome event: Results from the Medications Appl Ied a Nd Sus TAINed Over Time (MAINTAIN) registry

Current American College of Cardiology/American Heart Association guidelines recommend initiation or intensification of statin therapy to achieve low-density lipoprotein cholesterol (LDL-C) goals after an acute coronary syndrome (ACS), yet little is known about the actual practice of intensifying lipid-lowering (LL) therapy and LDL-C achievement from hospital admission to 1-year follow-up. The MAINTAIN registry enrolled ACS patients from January 2006 through September 2007, collecting data on statin formulation, dose, and lipid profiles at both baseline and 12 months. Statin intensity (estimated LDL-C lowering) was categorized by formulation and dose as either moderate (<40%) or intensive (≥40%). In-hospital LL intensification is described and LDL goal attainment is reported for patients with complete baseline and 12-month lipid panels. Of the 788 patients without contraindications to LL, 40% were on LL therapy before admission, and 89% at discharge. Among patients on LL therapy with LDL-C>100 mg/dL at admission, only 37% (n=38) had their LL therapy intensified. Among 382 patients with 12 months of data, 89% (n=341) were discharged on a statin. Of these, 89% were still on a statin at 12-month follow-up. A LDL-C goal of ≤100 mg/dL was achieved in 71% of patients, but the optional LDL-C goal≤70 mg/dL was achieved in only 31%. Most high-risk ACS patients are prescribed statin therapy at hospital discharge and remain on therapy at 12-month follow-up. Despite this, the LDL-C goal of ≤70 mg/dL is achieved in a small minority. There is substantial opportunity to intensify LL therapy after ACS to achieve guideline LDL-C goals and prevent future morbidity and mortality.

105 Finding the culprit of the culprit lesion: the relationship between maximum necrotic core site and minimum lumen area using virtual histology

Introduction In current practice angiographic assessment of the culprit lesion is the main approach to planning the percutaneous revascularisation strategy in high-risk acute coronary syndromes (ACS) patients. Previous histopathology studies in ACS patients have highlighted the presence of multiple vulnerable plaques along the length of the proximal coronary tree. Furthermore, it is suggested that the most vulnerable part of a culprit lesion does not occur at the most stenotic point, as it may lie in adjacent remodelled disease, not visualised by conventional angiography. We determined the relationship of the most vulnerable region to the minimum lumen area using intravascular ultrasound derived virtual histology (IVUS-VH) and compared this to areas of non-culprit disease. Methods This was a single centre, prospective, observational study that had received local ethical approval. The CL was predetermined by two operators based upon ECG changes and angiographic appearance. Successful IVUS-VH imaging of the entire culprit lesion (CL) (n=15) and non-culprit disease (NCD) (n=15) was undertaken using a phased array catheter (EagleEye catheter, 2.9 F/20 MHz; Volcano Corp) with a continuous motorised pullback of 0.5 mm/s. The plaque composition and analysis was determined by off-line analysis (PC VIAS 3.0.394 software; Volcano Corporation). Plaque constituents were measured over the entire length of a lesion and each individual frame of IVUS-VH was analysed to find the position of both the Minimum Lumen Area (MLA) and the distance to the site of maximum necrotic core % (MAX NC). Necrotic core is the IVUS-VH interpretation of high risk histological tissue that is soft, has no real structure and contains dead cells. Results A total of 30 lesions and 1774 IVUS-VH frames were included in the analysis. The mean length of the segment analysed in millimetres (mm) did not differ between the two groups (CL=30.5±11.7 vs NCD=25.6±11.9 p=0.18) all of the MAX NC sites lay proximal to the lesion MLA. In the CL the following percentages of MAX NC frames were within the following distances from the MLA: 0–5 mm (26.7%) 5–10 mm (26.7%) 10 mm+(46.7%). The mean distance at which the MAX NC site lay proximal to the MLA site in the CL was 10.4±8.9 mm (95% CI 5.5 to 15.3). For NCD this distance was statistically less at 4.6±2.9 (95% CI 3 to 6.3) p=0.03. MAX NC frames were positioned at the following distances: 0–5 mm (53.3%) 5–10 mm (46.7%). Conclusions Angiographic assessment alone cannot define the full extent of the culprit lesion. Generally, the most vulnerable areas of plaque are remotely positioned from the most stenotic region. In some cases 46.7% are over 10 mm proximal. Inadequate lesion coverage due to inappropriate stent length selection and placement in the culprit lesion (‘longitudinal geographic miss’) may be one explanation for the significant recurrent event rate in high-risk ACS patients.

AS-6: High-Risk Acute Coronary Syndrome Patients Benefit from Early Intervention within 24 Hours

Recent studies have demonstrated the benefits of an early invasive strategy for patients presenting with high-risk acute coronary syndrome (ACS). However, it is unclear whether there is incremental benefit if cardiac catheterization (CATH) is performed within 24 hours. The aim of this study is to determine whether patients with high-risk ACS who undergo early (<24 hours) compared with routine (>24 hours) intervention have improved clinical outcome.