NSTE Acute Coronary Syndromes Research Articles

Comparison of ticagrelor and prasugrel just before PCI in NSTE acute coronary syndromes, LIKE-ACCOAST analysis

Abstract Background Recommendations for the preference of prasugrel over ticagrelor just before PCI in NSTE ACS are based on limited and controversial evidence. Furthermore, prasugrel can’t be used in patients after a stroke/TIA, and the risk of bleeding in older and low-weight patients annuls its benefit. Purpose We aimed to add to the current evidence comparing the benefit of prasugrel and ticagrelor just before PCI (without pretreatment) in NSTE ACS patients. Methods The prasugrel population comprised the ACCOAST study non-pretreatment arm undergoing PCI (N 1372) (ref 1). The ticagrelor study population was selected from the long-term all-comers National Registry of Cardiovascular Surgery and Interventions: Module of Cardiovascular interventions of Institute of Health Information and Statistics of the Czech Republic (N 15126)who were 1) undergoing PCI for NSTE ACS, 2) received ticagrelor loading dose 180 mg just before the procedure, 3) fulfilled the inclusion and exclusion criteria of the ACCOAST trial (N 1370). The endpoint (identically to the ACCOAST primary EP) was a composite of cardiovascular death, myocardial infarction, stroke, urgent revascularization, or glycoprotein IIb/IIIa bailout seven days after PCI. The data were matched to the structure of published ACCOAST no pre-treatment group using R with maic package, which provides a generalized workflow for the generation of subject weights to be used in Matching-Adjusted Indirect Comparison (MAIC) (Ref 3,4). In MAIC, unbiased comparison between outcomes of two trials is facilitated by weighting the subject-level outcomes of one trial with weights derived such that the weighted aggregate measures of the prognostic or effect modifying variables are equal to those of the sample in the comparator trial. Results The study population characteristics are presented in Table. We did not find any difference in the efficacy endpoint at seven and 30 days after PCI between the groups treated with prasugrel and ticagrelor (Figure). Conclusion Prasugrel and ticagrelor given just before PCI for NSTE ACS are equally effective in reducing ischemic risk.Table.Efficacy endpoint occurence.

C54 ACUTE AND LONG TERM PERFORMANCE OF MAGMARIS BIORESORBABLE SCAFFOLD IMPLANTATION IN SPONTANEOUS CORONARY ARTERY DISSECTION (SCAD): THE EXPERIENCE OF THE COORDINATOR CENTER OF THE INTERNATIONAL MULTICENTER REGISTRY DISCO

Abstract Background Spontaneous Coronary Artery Dissection (SCAD) is a challenging clinical scenario and represents an increasingly studied cause of acute coronary syndrome (ACS). An interventional strategy in these cases remains controversial since it may require an extensive permanent metallic stenting of vessel to seal the dissection with a non negligible rate of complications. Moreover, SCAD patients are usually young women with non–calcified disease where Bioresorbable Scaffolds (BrS) may be an intriguing option. Methods DISCO IT/SPA is a International observational registry which retrospectively enrolled patients admitted with a diagnosis of SCAD across 26 Italian and Spanish centers. Baseline, procedural characteristics, in–hospital management and outcomes of 369 SCAD patients were collected, of these 12 patients were treated with PCI with BrS MAGMARIS at the coordinator center of Rivoli and Orbassano. Major cardiovascular events (MACEs) were defined as the composite of cardiovascular death, non–fatal Myocardial infarction (MIs) and any PCI performed. Results In our cohort of SCAD patients treated with BrS there was a slight prevalence of women (n=7, 58,3%) with an average age of 50,9±7,4 years. NSTE–ACS was the most common clinical presentation (83,3%), followed by STEMI (16,7%). In 7 patients the first treatment choice for SCAD was PCI with BrS deployment, in 5 patients BrS were deployed during hospitalization for unplanned PCIs (four of them) and after one month for a MI due to SCAD recurrence in the last patient. Multivessel disease was present only in one case and LAD–DG was the main vessel affected (n=10, 83,3%). SCAD type 2A was the most frequent (41,7%). Intravascular imaging was performed in 10 cases (83,3%) and procedural success was achieved in all cases. Angiographic follow–up was obtained in 9 patients (75%), through coronary angiogram (n=8) or CT scan (n=1), at a mean length of 5,2±5,6 months. In–hospital MACE were 5 (23,8%) but none of them occurred after BrS deployment. The only MACE reported after BrS deployment was an unplanned PCI for SCAD progression. Conclusions In SCAD bioresorbable scaffolds represent an excellent option to preserve the natural physiology of the coronary vessels. Notably, in our cohort we reported a very high procedural success rate in PCI assisted in large part by intracoronary imaging. Further studies with larger numerosity are needed to demonstrate the advantages of this type of scaffold in these patients.

C-reactive protein and uric acid roles in distinguishing ST-segment elevation myocardial infarction from non-ST-elevation acute coronary syndrome

ABSTRACT Acute coronary syndrome (ACS) is defined as a range of conditions which the blood flow to the heart was reduced or stopped. This disorder is correlated to a systemic inflammatory response and some biochemical factors. Therefore, the aim of this study was investigations of serum C-reactive protein (CRP) and uric acid levels in ST-segment elevation myocardial infarction (STEMI) and non-ST-elevation ACS (NSTE ACS), as common subtypes of ACS. Patients with ACS (n = 140) were assessed with coronary arteriography and divided into STEMI and NSTE ACS groups. The serum levels of hs-CRP and uric acid were investigated using a routine clinical chemistry analyzer. Patients with STEMI showed a significant increase in uric acid level compared to those with NSTE ACS (P < .0001). Other data indicated that hs-CRP level in patients with STEMI was significantly higher than individuals with NSTE ACS (P < .0001). Modeling analysis revealed that the increased levels of acid uric and hs-CRP in patients with STEMI were independent of the effects of age, gender, background diseases, and familial history (P < .001). The current study provides further evidence to indicate that hs-CRP and uric acid may be considered as biofactors for comparing STEMI from NSTE ACS and determining disease outcome.

Association between Myocardial Performance Index (Tei- Index) and Severity of Coronary Artery Disease in Patients with Non-ST Segment Elevation Acute Coronary Syndrome

Background and objectives: Evaluation of ventricular systolic and diastolic functions is an essential part of echocardiographic evaluation in a patient of acute coronary syndrome (ACS). Myocardial Performance Index (MPI), also known as the Tei index, reflects both systolic and diastolic function of the left ventricle. The aim of this study was to see the association between myocardial performance index and severity of coronary artery diseases assessed by the gensini score (GS) in patients with non-ST segment elevation acute coronary syndrome. Methods: This cross-sectional study included a total 135 patients with NSTE ACS who underwent coronary angiography. MPI was measured using Pulse-Wave Doppler in all patients before coronary angiography. The patients were divided into three groups according to the Gensini score (GS); low GS &lt; 19 (n=23); mid GS ³19 and £96 (n= 76); high GS &gt; 96 (n=36) on CAG. Baseline characteristics, MPI parameters &amp; GS were then compared between the three groups. Results: MPI was obtained successfully in 135 patients. MPI parameter was significantly increased with increased GS. MPI was positively correlated with the GS (r = 0.40, p &lt; 0.001) Binary logistic regression analysis showed that MPI was strongly associated of severity of coronary artery disease assessed by GS (b = 3.766, p &lt; 0.001). Conclusion: Patients with NSTE-ACS with severe coronary artery disease may be identified by means of MPI measurement. Key words: Tei Index, Gensini Score, Non-ST Segment Elevation Acute Coronary Syndrome, Coronary Angiogram. Bangladesh Heart Journal 2022; 37(1): 16-26

Level of serum matrix metalloproteinase-9 in patients with acute coronary syndrome in Vietnam

Acute Coronary Syndrome (ACS) is one of the foremost causes of mortality and morbidity worldwide as well as Vietnam. ACS was evoked by rupture or erosion of atherosclerotic plaques that was divided into Non–ST-segment elevation Acute Coronary Syndrome (NSTEACS) and ST-segment elevation myocardial infarction groups (STEMI). The matrix metalloproteinase (MMPs) is an enzyme family with fucntioning in the degradation of extracellular matrix and disruption of basement membranes. Of the MMPs, MMP-9 is expressed in the atherosclerotic plaques and plays a key role in the rupture of vulnerable atherosclerotic plaques. In this work, we measured the serum MMP-9 level in 205 patients with acute coronary syndrome (including 103 of NSTE-ACS and 102 of STEMI patients) and 101 healthy participants by sandwich Elisa method. The results showed that the MMP-9 level was significantly higher in NSTE-ACS and STEMI compared to the control group (208.59 ± 100.47 ng/mL, 189.98 ± 112.81 ng/mL vs 168.50 ± 79.52 ng/mL, respectively, P=0.014). However, a logistic regression analysis indicated that the MMP-9 level was only significantly higher in patients with NSTE ACS (OR= 1.0048, CI 95%= 1.000-1.009; P= 0.018). The serum MMP-9 level is correlated with traditional risk factors such as glucose, Cholesterol and Triglyceride by multiple logistic regression analysis. Conclusion: Our study suggests that the serum MMP-9 level is significantly associated with the NSTEACS and is a potential marker for dianogsis of ACS in the Vietnamese patients

Management of Acute Coronary Syndromes

Management of Acute Coronary Syndromes

Risk stratification in non-ST elevation acute coronary syndromes: searching for the right formula

This editorial refers to ‘Risk stratification of patients undergoing medical therapy after coronary angiography’†, by N. Bettinger et al ., on page 3103. Medicine is the science of uncertainty and the art of probabilityWilliam Osler Enormous progress has been made in the diagnosis and treatment of acute coronary syndromes (ACS) over the past two decades. The emergence of timely reperfusion therapy, in concert with the relatively specific and characteristic ECG calling card of ST elevation, has remarkably improved the outcome of patients with ST elevation myocardial infarction. As Osler opined, however, there remains less certainty about the right formulation for the diagnosis and therapy of the much larger and more heterogeneous cohort of patients with non-ST elevation ACS (NSTE ACS). In part this relates to the development of high sensitivity troponin assays that have shifted the classification of many patients from the unstable angina category to those with small—but apparently prognostically relevant—myocardial infarctions.1 The emergence of other biomarkers, quantitative ECG analysis, and myocardial imaging have also added welcome granularity to the early assessment of outcomes.2,3 Given the wide spectrum of new antithrombotic and antiplatelet therapies, coupled with advances in coronary interventions, physicians must undertake timely management decisions that have potential benefit and risk as well as major resource implications. Hence current guidelines place strong emphasis on early risk stratification to aid in timely triage: those with intermediate …

Abstract 13846: The Relationship of Platelet Function Measurements with Bleeding Outcomes During Long-term Treatment with Dual Antiplatelet Therapy in Medically Managed NSTE-ACS Patients

Introduction: The relationship of low “on-treatment” platelet reactivity to longitudinal risks of major bleeding following acute coronary syndromes (ACS) has not been clearly delineated. Methods: We analyzed 2428 patients with non-ST-elevation ACS (NSTE ACS) from the TRILOGY ACS trial who were managed without revascularization and had platelet reactivity measurements (P2Y12 reaction units [PRUs]) collected in a platelet function substudy. Patients received aspirin + prasugrel (10 mg/d; 5 mg/d for those ≥75 y or &lt;75 y and &lt;60 kg) or clopidogrel (75 mg/d). Non-CABG severe/moderate GUSTO bleeding and non-CABG TIMI major/minor bleeding were ascertained through 30 months. Contal’s method was used to investigate whether a PRU cut point could distinguish high vs low bleeding risk. Multivariable Cox proportional hazard models were used to evaluate the association between PRU and time to first bleed. Results: Through 30 months, there were 27 GUSTO severe/moderate bleeds and 37 TIMI major/minor bleeds, with gastrointestinal bleeding the most common. Baseline characteristics were stratified by tertiles of PRU values at 5 d, and significant differences were seen across tertiles (Table). Unadjusted bleeding rates appeared highest among those in the lowest PRU tertile but no reliable PRU cut point was found that significantly distinguished bleeding risk. Unadjusted analyses showed continuous measures of PRUs were not associated with GUSTO (HR=1.00, 95% CI: 0.96-1.04) or TIMI bleeding (HR=1.03, 95% CI: 0.99-1.06). This relationship did not change after multivariable adjustment. Conclusions: Among NSTE-ACS patients managed without revascularization and receiving dual antiplatelet therapy, PRU values were not significantly associated with long-term bleeding risk. The relatively small number of bleeding events accrued limited study power, but these results suggest that low “on-treatment” platelet reactivity does not independently predict post-ACS bleeding risk.

Clopidogrel pretreatment effect according to the clinical presentation in patients undergoing percutaneous coronary intervention: a meta-analysis

Purpose: Although Clopidogrel pretreatment is recommended for Acute Coronary Syndrome (ACS) and stable coronary patients scheduled for Percutaneous Coronary Intervention (PCI), the benefit of this strategy compared to an administration at the time of PCI has not been shown on hard clinical outcome. In this new analysis, we performed a systematic review and meta-analysis of all randomized placebo-controlled trials (RCTs) and registries to evaluate the impact of clopidogrel pretreatment on mortality, MACE and major bleeding after PCI, as compared with no pretreatment. Methods: We included studies from MEDLINE, EMBASE, Cochrane Controlled Trials Register databases and references lists of qualifying articles that reported clinical data on mortality and major bleeding. A random-effect model was applied. Pretreatment was defined as the administration of clopidogrel before PCI or catheterization. The primary efficacy and safety endpoints were all-cause mortality and major bleeding, respectively. Results: Of the 392 titles identified, 15 articles met the inclusion criteria, published between August 2001 and September 2012, including 37 914 patients: 13 628 patients with stable coronary artery disease (CAD), 15 650 with Non ST Elevation ACS (NSTE ACS) and 8 536 with ST elevation ACS (STEMI) presentation. Results for Death, Major Bleeding and MACE are shown in Figure I. ![Figure][1] Figure 1. Main ischemic and bleeding end point Conclusion: Among patients scheduled for PCI, clopidogrel pretreatment was not associated with a lower risk of mortality nor with an increase in major bleeding overall but with differential effect according clinical presentation. Only STEMI patients undergoing primary PCI appear to draw a benefit from pre treatment with clopidogrel. In other patients, treatment at the time of PCI appears to be sufficient. [1]: pending:yes

TRIOLOGY ACS: No benefit/No harm

[first paragraph of article] Potent and consistent P2Y12 receptor inhibition is associated with reduced risk of atherothrombotic events in patients presenting with acute coronary syndromes (ACS), but with inevitable increased risk of bleeding as demonstrated in TRITON and PLATO trials – a finding that is especially pertinent to the treatment of medically managed NSTE ACS patients, who typical have a greater burden of comorbidities that predispose to bleeding. Given the significant proportion of non-ST elevation myocardial infarction (NSTE) ACS patients managed medically worldwide and the need to mitigate both ischemic and bleeding risks in this vulnerable, high-risk population, novel clinical trials are needed.

Management of Acute Coronary Syndromes

Management of Acute Coronary Syndromes

THE EFFECTS OF 80 MG LOADING DOSE ATORVASTATIN PRETREATMENT ON MYOCARDIAL PROTECTION DURING PERCUTANEOUS CORONARY INTERVENTION IN ELDERLY PATIENTS WITH NON-ST-SEGMENT ELEVATION ACUTE CORONARY SYNDROME

ObjectivesThis study was designed to evaluate the peri-procedural myocardial injury and safety profile of atorvastatin in patients over 70 years old with non-ST segment elevation acute coronary syndromes (NSTEACS).MethodsA total...

Treatment with tirofiban for acute coronary syndrome (ACS): a systematic review and network analysis

Objective:To assess the efficacy of tirofiban in comparison to usual care or other GPIIb/IIIa antagonists (eptifibatide and abciximab). Results were analysed by drug administration with planned percutaneous coronary intervention (PCI) or as medical management without planned PCI, and separately for STEMI or NSTE ACS patients.Research design and methods:A systematic review was performed of randomized controlled trials of tirofiban, abciximab, eptifibatide or usual care given to patients with acute coronary syndrome. Nine databases were searched up to March 2010. Pair-wise meta-analysis was used to combine all available direct comparisons; indirect comparisons and network analysis were performed when this was not possible. The primary outcome was MACE (major adverse cardiac event).Results:The search yielded 8, 119 records and 50 trials were included (total number of patients = 52,958). Compared to usual care, high and medium-dose tirofiban (25 and 10 µg/kg/min) administered with planned PCI reduced MACE at 30 days for patients with STEMI (RR 0.67, 95% CI 0.45, 0.99; RR 0.28, 95% CI 0.10, 0.80), but was not effective as a medical management. Medium-dose tirofiban (10 µg/kg/min) administered with planned PCI or low dose (0.4 µg/kg/min) as medical management reduced the risk of MACE for patients with NSTE ACS (RR 0.39, 95% CI 0.21, 0.75; RR 0.58, 95% CI 0.41, 0.83) in comparison to usual care, but at the expense of increased thrombocytopenia (RR 3.26, 95% CI 1.31, 8.13). Evidence from RCTs and network analysis indicated tirofiban and abciximab were equally effective and safe. Comparing tirofiban and eptifibatide treatment by indirect and network analysis produced inconclusive results.Conclusions:Tirofiban was more effective than usual care for STEMI and NSTE ACS patients receiving planned PCI, and NSTE ACS patients receiving medical management. Tirofiban and abciximab were equally effective. Comparisons of tirofiban and eptifibatide were inconclusive.

Effects of loading dose of atorvastatin before percutaneous coronary intervention on periprocedural myocardial injury

To investigate the effects of loading dose of atorvastatin on periprocedural myocardial injury and inflammatory reaction in patients with non-ST segment elevation (NSTE) acute coronary syndromes (unstable angina or NSTE acute myocardial infarction). A total of 81 patients with NSTE-acute coronary syndromes were randomly divided into the pretreatment with atorvastatin group [80 mg 12 h before percutaneous coronary intervention (PCI), with a further 40 mg preprocedure dose] (n=41) or the placebo group (n=40). The main end point was a 30-day incidence of major adverse cardiac events (cardiac death, nonfatal acute myocardial infarction, or revascularization with either PCI or coronary artery bypass grafting). Creatine kinase-MB, cardiac troponin I, and high-sensitivity C-reactive protein levels were measured at the baseline and at 8 and 24 h after the procedure. Major adverse cardiac events occurred in 2.4% of patients in the atorvastatin group and 22.5% of those in the placebo group (P=0.0161). This difference was mostly because of reduction in the incidence of myocardial infarction (2.4 vs. 20.0%; P=0.0307). Markers of the two groups were elevated after PCI; however, the higher values of creatine kinase-MB, cardiac troponin I, and high-sensitivity C-reactive protein in the atorvastatin treatment group were significantly lower than those in the placebo group (P<0.01). Short-term pretreatment with a high dose of atorvastatin significantly reduces procedural myocardial injury in early PCI.

Influence of transfer-in rates on quality of care and outcomes at receiving hospitals in patients with non–ST-segment elevation myocardial infarction

Patients with non-ST-segment elevation myocardial infarction (NSTEMI) are frequently transferred to tertiary hospitals for angiography and/or revascularization from hospitals lacking such capabilities. Given that patients who undergo invasive cardiac procedures are younger and have fewer comorbidities compared with those managed medically, the relative proportion of transfer-in patients at tertiary hospitals may influence comparisons of quality and guidelines adherence. We evaluated 142,092 NSTEMI patients treated at 396 revascularization-capable sites in the CRUSADE National Quality Improvement Initiative from 2001 to 2006. Transfer-in patients were included if they arrived at the receiving hospital after their first presentation to a different hospital. Hospitals were categorized into tertiles based upon their transfer-in rates (low, intermediate, and high) and adherence to practice guidelines recommendations for NSTEMI. In-hospital clinical outcomes were compared across hospital tertiles. Acute and discharge composite guidelines adherence scores improved at hospitals with an increasing proportion of transfer-in patients, both for transferred as well as for directly admitted patients. These better adherence scores were inversely associated with overall mortality, with the lowest mortality observed in patients at hospitals with the highest transfer-in rates. However, once adjusted for baseline confounders, the mortality rates for patients in the hospitals in the highest transfer-in tertile did not differ significantly compared with the sites in the lowest transfer-in tertile (odds ratio 1.02, 95% CI 0.90-1.16). Our findings show that the proportion of NSTEMI patients transferred into revascularization-capable hospitals varies significantly. Hospitals with a higher proportion of transfer-in patients tend to provide higher overall quality of NSTE acute coronary syndrome care; they also have lower overall in-hospital mortality, which may, in part, be related to the lower-risk baseline characteristics of patients at these hospitals.

Abstract 5495: More Rapid and Consistent Inhibition of Platelet Aggregation is Achieved by Loading With Ticagrelor Compared to Clopidogrel in Patients With Acute Coronary Syndromes: Results From the PLATO PLATELET Substudy

Background: Ticagrelor (T) is an oral reversible P2Y 12 receptor antagonist that does not require conversion to an active metabolite for antiplatelet activity, unlike clopidogrel (C). The PLATO study compared the efficacy of T and C in patients with a broad range of acute coronary syndromes (ACS). In this substudy (PLATO PLATELET), we assessed the onset and extent of inhibition of platelet function in PLATO study patients. Methods and Results: 24 C-naive patients with NSTE ACS or STEMI undergoing primary PCI and sequentially randomised in a double blind, double dummy design to C (300mg [n=7] or 600 mg load [n=5]) or T (180mg load [n=12]) in the PLATO study in a single centre were entered into the first phase of PLATO PLATELET. Light transmittance aggregometry (LTA) with ADP (5 and 20 uM) and whole blood single platelet counting aggregometry (WBSPC) using ADP 1–100 uM was performed prior to study drug administration and 1, 2, 4, 8 and 12 hours after study drug. VerifyNow P2Y12 (VN) and VASP assays were also performed pre and 4h post study drug. Data obtained after abciximab administration was excluded except for VASP data. There was more rapid and greater inhibition of platelet aggregation with T vs C, with most T-treated patients showing a substantial effect at 1h post dose that was sustained until 12h post dose (Figure ). VN data at 4h were 273±124 and 68±97 PRU for C and T respectively (p&lt;0.01). VASP data showed a similar trend. C 300 vs 600mg doses showed the same patterns of LTA response. Conclusion: T 180mg loading dose has a faster onset of action with greater inhibition of platelet function compared to C in patients with ACS. WBSPC and VN can rapidly assess the early effects of P2Y 12 antagonists.

Characterization and outcomes of women and men with non–ST-segment elevation myocardial infarction and nonobstructive coronary artery disease: Results from the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines (CRUSADE) Quality Improvement Initiative

Women with non-ST-segment elevation myocardial infarction (NSTEMI) who undergo coronary angiography have no obstructive coronary lesions more often than men. Sex-specific characteristics and outcomes of patients without obstructive coronary artery disease (CAD) have not been described previously. Using data from NSTEMI patients enrolled in CRUSADE from 2001 to 2005, we evaluated differences in clinical features and in-hospital outcomes between men and women with no obstructive CAD. After excluding patients with missing catheterization and sex data (n = 1,494), previous coronary artery bypass grafting or percutaneous coronary intervention (47,907), catheterization contraindications (n = 6,588), and missing obstructive CAD status (n = 1,565), there were 55,514 patients (68.4%) with NSTE acute coronary syndromes (ACS) who underwent angiography (among women, 62.1% [21,294/34,290], and among men, 73% [34,220/46,875]; P < .001). Among these, a total of 5,538 patients (10.0%) had nonnonobstructive CAD-15.1% (3,221/21,294) of women and 6.8% (2,317/34,220) of men (P < .0001). In patients without obstructive CAD, women were as likely as men to have MI (troponin elevation in 89% vs 87%, P = .37). Women and men were equally likely to have larger troponin elevations (58.9% vs 58.6% with troponin >5x upper limit of normal, P = .69, respectively). In NSTEMI patients without obstructive CAD, in-hospital death (0.6% women vs 0.7% men) and cardiogenic shock (1.0% women vs 0.7% men) were infrequent. Among NSTE ACS patients undergoing coronary angiography, absence of obstructive CAD is more common in women than men. Although nonobstructive CAD was twice as common among women with NSTEMI, sex differences in characteristics and outcomes were similar to those found with obstructive CAD. Unadjusted in-hospital outcomes of NSTEMI patients with nonobstructive CAD are favorable in both sexes. Whether the underlying pathophysiology of NSTE ACS without documentation of obstructive CAD is different between women and men requires further study.

Relationship between renal function and outcomes in high-risk patients with non-ST-segment elevation acute coronary syndromes: Results from SYNERGY

BackgroundChronic kidney disease (CKD) is a risk factor for coronary heart disease and bleeding with antithrombotic therapy in patients with acute coronary syndromes (ACS). We evaluated the effect of renal function on efficacy and outcomes in high-risk patients with NSTE ACS in the SYNERGY trial. MethodsCreatinine clearance (CrCl) at the time of randomization was analyzed as a continuous variable added to multivariable logistic regression models for 30-day death or MI, non-CABG-associated TIMI major bleeding, GUSTO severe bleeding, and transfusion in the overall study population, patients undergoing coronary angiography, and patients undergoing PCI. ResultsOf 9838 patients with a CrCl value, 70.6% (N=6950) had CrCl≥60 mL/min, 27.8% (N=2732) had CrCl 30–59 mL/min, and 1.6% (N=156) had CrCl<30 mL/min. No randomized treatment by CrCl interaction test was found to be statistically significant, suggesting renal insufficiency affected enoxaparin and unfractionated heparin outcomes similarly. After adjustment, CrCl was an independent predictor of 30-day death or MI (OR 1.06, 95% CI 1.03–1.09), TIMI major bleeding (OR 1.06, 95% CI 1.02–1.10), GUSTO severe bleeding (OR 1.10, 95% CI 1.03–1.17), and transfusion (OR 1.07, 95% CI 1.04–1.11). ConclusionsPatients with CKD had higher rates of 30-day death or MI and bleeding than those without CKD, regardless of randomized antithrombin therapy. While this analysis suggests that there is a rise in bleeding events as CrCl falls for patients in either treatment group, it is unknown whether a reduction in dose would decrease bleeding risk.

Characterizing Young Patients With Diabetes and Non–ST-Segment Elevation Acute Coronary Syndromes

Most information regarding the prognosis and quality of care of patients with diabetes and acute coronary syndromes (ACSs) is derived from studies that have largely focused on middle-aged and older populations (1–3). Thus, data regarding the presenting features, treatment patterns, and outcomes in smaller proportions of ACS patients with diabetes who are young (an age wherein insulin-dependent diabetes manifests, often portending poor prognosis) has been less well characterized. Accordingly, we sought to evaluate clinical features, management, and in-hospital clinical events among young patients (aged ≤45 years) with and without diabetes who presented with non–ST-segment elevation ACS (NSTE ACS) and who were included in the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines?) Quality Improvement Initiative (4–6). The details of the CRUSADE Initiative have been previously published (4–6). In brief, patients included in the CRUSADE Quality Improvement Initiative were admitted to 498 participating U.S. hospitals with ischemic symptoms at rest within 24 h before presentation and high-risk features including ST-segment depression, transient ST-segment elevation, and/or positive cardiac markers (elevated troponin I or T and/or creatine kinase-MB more than the upper limit of normal for participating institutions). For this study, we analyzed data from 9,643 patients aged ≤45 years out of …

Inflammatory Biomarkers in Acute Coronary Syndromes

The inflammatory etiology of atherosclerosis has prompted a search for biomarkers of inflammation that predict risk for coronary artery disease and its sequelae. Within the acute coronary syndromes (ACS), inflammatory biomarkers may provide independent information regarding pathophysiology, prognosis, and optimal therapeutic strategies. On the basis of the hypothesis that different pathophysiological processes provide nonoverlapping information regarding risk stratification and disease management, this review series addresses biomarkers for each step in the inflammatory process that leads to ACS. Part I reviewed cytokines; this part reviews acute-phase reactants and biomarkers of endothelial cell activation; subsequent parts will address biomarkers of oxidative stress, angiogenesis, extracellular matrix degradation, and platelet activation. In the acute-phase response, cytokines drive production of acute-phase reactants, defined by >25% change in circulating concentration during an inflammatory response. These markers may also remain elevated chronically because of continuing inflammatory stimuli (Table). View this table: Inflammatory Biomarkers in ACS ### C-Reactive Protein C-reactive protein (CRP) is a pentraxin acute-phase protein, members of which are evolutionarily conserved in most vertebrates.1 Hepatocytes and possibly smooth muscle cells and macrophages transcriptionally activate production of CRP in response to inflammatory cytokines, including interleukin-1 and interleukin-6.2 CRP is a robust clinical marker because of its stability, reproducible results, and ease of assay. Although it was originally proposed as a nonspecific marker of inflammation, several reports suggest that CRP may play a direct pathophysiological role in the development and progression of atherosclerosis. Proposed mechanisms include induction of endothelial dysfunction,3 promotion of foam cell formation,4 inhibition of endothelial progenitor cell survival and differentiation,5 and activation of complement in atherosclerotic plaque intima6 and ischemic myocardium.7 Patients with ACS have elevations in CRP in association with their presenting symptoms. There appears to be a bimodal CRP response among patients with ACS. In some patients, CRP may remain elevated for …