Six-month outcomes of percutaneous coronary balloon angioplasty in acute coronary syndromes: Results from the PURSUIT trial

BACKGROUND: Potent inhibition of the platelet glycoprotein IIb/IIIa receptor has improved the acute outcome of patients presenting with acute coronary syndromes (ACS). For patients with ACS undergoing percutaneous balloon angioplasty without coronary stenting in the era of platelet glycoprotein IIb/IIIa blockade, the long-term prognosis is less clear. OBJECTIVE: To examine the six-month outcome of patients who received eptifibatide within a randomized clinical trial and subsequently underwent balloon angioplasty. METHODS: Patients included in this substudy were enrolled in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, a randomized study evaluating the efficacy of eptifibatide in reducing the incidence of death or nonfatal myocardial infarction (MI) in non-ST segment elevation ACS. During the index hospitalization, 1151 (12.2%) of the PURSUIT patients underwent percutaneous balloon angioplasty without coronary stenting. RESULTS: Eptifibatide was associated with a significant reduction in the adjudicated composite end point of death or MI at six months after randomization in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) (P=0.037). A trend toward a beneficial effect was evident before the procedure (4.7% versus 6.9%; P=0.13) and at 30 days (12.1% versus 15.3%; P=0.12). The incidence of repeat revascularization was relatively low for patients undergoing PTCA, with no difference observed between the eptifibatide and placebo groups (16.3% versus 14.8%; P=0.51). CONCLUSIONS: Eptifibatide was associated with a sustained beneficial effect to six months in patients with ACS undergoing PTCA. It reduced the incidence of preprocedural MI. The rate of repeat revascularization at six months was low and was not significantly altered by eptifibatide.     

Persistent platelet activation is related to very early cardiovascular events in patients with acute coronary syndromes

INTRODUCTION: Persistent platelet function while on antiplatelet therapy affects outcomes in patients with acute coronary syndromes (ACS). AIM: To evaluate whether platelet reactivity measured by collagen-epinephrine (CEPI) or collagen-ADP (CADP) closure times (CT) with Platelet Function Analyzer 100 (PFA-100) is related to very early, in-hospital cardiovascular events in patients with ACS. METHODS: The study included 91 patients with ACS undergoing percutaneous coronary intervention (PCI) with stent implantation who were treated with aspirin and clopidogrel. Patients were stratified in accordance with both CEPI-CT (<190 s or >190 s), reflecting aspirin resistance, and our own cut-off point for CADP-CT measured at a mean of 6 days after admission. In-hospital events included re-infarction, cardiac arrest, recurrent angina, severe arrythmias, pulmonary oedema and cardiogenic shock. RESULTS: Patients were divided into 4 study groups: group 1 with CADP-CT <104 s (n=10, 11.0%), group 2 with CEPI-CT <190 s (n=10, 11.0%), group 3 with CADP-CT <104 s and CEPI-CT <190 s (n=9, 9.9%) and a control group with both CT values above the cut-off limits (n=62, 68.1%). The baseline clinical characteristics and received treatment of each subgroup were similar. A test for a trend between controls, group 1 or 2 and group 3 disclosed statistical significance (p <0.001). When analysed separately, only patients from group 3 had a higher incidence of negative outcomes compared to controls (p <0.005; relative risk RR - 9.0; 95% CI 2.4-33.9). CONCLUSIONS: Enhanced platelet function after PCI when measured under high shear rates by both PFA-100 cartridges is independently associated with the most unfavourable in-hospital clinical outcome.     

Autoantibodies to phosphorylcholine and cardiovascular outcomes in patients with acute coronary syndromes in the ATLAS ACS-TIMI 46 trial

Atherogenesis is a complex inflammatory process stemming from the accumulation and oxidation of low density lipoproteins (LDL). IgM autoantibodies against phosphorylcholine (anti-PC) bind to the PC epitope on oxidized LDL (OxLDL), inhibiting the uptake of oxLDL by macrophages in atherosclerotic lesions. Anti-PC autoantibodies have been reported to be protective against atherothrombosis. We investigated the relationship of anti-PC concentrations with cardiovascular outcomes in patients with acute coronary syndromes (ACS). We measured anti-PC levels within 7 days of an ACS in 3,356 patients enrolled in the ATLAS ACS-TIMI 46 trial, a randomized dose ranging study of rivaroxaban versus placebo. The primary endpoint was death, myocardial infarction (MI), stroke, or severe recurrent ischemia (SRI) requiring revascularization during 6 months. The median baseline anti-PC concentration was 40.9 U/mL (25th, 75th percentiles: 25.4, 67.4). There was no significant association between anti-PC levels and the primary endpoint (Q1: 6.8 %, Q2: 4.2 %, Q3: 7.8 %, Q4: 5.4 %, p-trend = 0.87), all-cause mortality (Q1: 1.4 %, Q2: 0.7 %, Q3: 2.4 %, Q4: 0.9 %, p-trend = 0. 96), or any of the other individual endpoint components (MI: p-trend = 0.87, Stroke: p-trend = 0.43, SRI: p-trend = 0.66). Using the previously reported anti-PC cutpoint of 17 U/mL did not reveal a significant relationship between anti-PC concentrations and cardiovascular outcomes (<17 U/mL: 8.1 % vs. ≥17 U/mL: 5.8 %; p = 0.11). Similarly, evaluation of anti-PC as a continuous variable did not reveal a significant association (p = 0.30). In this study of patients early after ACS undergoing intensive secondary preventive therapy, IgM anti-PC titers did not exhibit a significant relationship with cardiovascular outcomes.     

Outcomes with the paclitaxel-eluting stent in patients with acute coronary syndromes: analysis from the TAXUS-IV trial

OBJECTIVES: We sought to investigate the outcomes of paclitaxel-eluting stent implantation in patients with unstable angina or non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention (PCI). BACKGROUND: Whether the paclitaxel-eluting stent is safe and effective in patients with acute coronary syndromes (ACS) is unknown. METHODS: In the TAXUS-IV trial, 1,314 patients with stable or unstable ischemic syndromes undergoing PCI were randomized to treatment with either the slow-release, polymer-based, paclitaxel-eluting TAXUS stent or a bare-metal EXPRESS stent (Boston Scientific Corp., Natick, Massachusetts). The results were stratified by the acuity of the presenting clinical syndrome. RESULTS: Acute coronary syndromes were present in 450 patients (34.2%), 237 of whom were assigned to paclitaxel-eluting stents and 213 to bare-metal stents. The baseline and procedural characteristics were well matched between the groups. Clinical outcomes at 30 days were similar with both stents. At one-year follow-up, patients with ACS assigned to the paclitaxel-eluting stent compared to the control stent had strikingly lower rates of target lesion revascularization (TLR) (3.9% vs. 16.0%, p < 0.0001) and major adverse cardiac events (11.1 vs. 21.7%, p = 0.002). By multivariate analysis, ACS was an independent predictor of in-stent restenosis in the cohort treated with bare-metal stents (hazard ratio [HR] = 2.03 [95% confidence interval (CI) 1.05 to 3.92], p = 0.035), while among patients randomized to the paclitaxel-eluting stents, ACS was an independent predictor of freedom from restenosis (HR = 0.27 [95% CI 0.08 to 0.97], p = 0.04). CONCLUSIONS: The use of the paclitaxel-eluting TAXUS stent was safe in patients with unstable ischemic syndromes, and was associated with marked reduction of ischemia-driven TLR and adverse cardiac events at one year.     

A platelet P-selectin test predicts adverse cardiovascular events in patients with acute coronary syndromes treated with aspirin and clopidogrel

Abstract

There is wide variation in response to antiplatelet therapy and high on-treatment platelet reactivity is associated with adverse cardiovascular events. The objective here was to determine whether the results of a novel strategy for assessing platelet reactivity (based on P-selectin measurement) are associated with clinical outcomes in patients with acute coronary syndromes (ACS). This was a prospective cohort study of 100 ACS patients taking aspirin and clopidogrel. P-selectin tests designed to assess response to P2Y₁₂ antagonists or aspirin were performed alongside light transmission aggregometry. For the P2Y₁₂ P-selectin test, an optimal cutoff for high platelet reactivity was determined by receiver operating characteristic (ROC) curve analysis. Patients were divided into two cohorts based on this value: patients with (n?=?42) or without (n?=?58) high platelet reactivity. The primary endpoint was defined as the composite of cardiovascular death, myocardial infarction and stent thrombosis. After 12 months, the primary endpoint occurred in 12 patients. ROC curve analysis determined that the P2Y₁₂ P-selectin test results were predictive of the primary endpoint (area under curve?=?0.69, p?=?0.046). The primary endpoint occurred more frequently in patients with high on-treatment platelet reactivity compared to those without (21.4% vs. 5.2%; hazard ratio (HR) 4.14; p?=?0.026). The P2Y₁₂ P-selectin test results correlated with light transmission aggregometry (Spearman p?<?0.0001). Using the Aspirin P-selectin test, only two patients demonstrated high on-treatment platelet reactivity. This study suggests that a P2Y₁₂ P-selectin test is capable of detecting high on-treatment platelet reactivity, which is associated with subsequent cardiovascular events.     

The role of cardiovascular magnetic resonance in patients with acute coronary syndromes

Cardiovascular magnetic resonance (CMR) imaging is a recognized technique for characterization of myocardial tissue in stable ischemic heart disease. In addition, CMR is emerging as a noninvasive imaging tool that can provide supporting information to guide treatment in acute coronary syndromes (ACSs). The advantages of using CMR acutely could potentially include triage/differential diagnosis in patients presenting with chest pain and troponin rise but without diagnostic electrocardiogram changes, assessment of severity of myocardial injury (irreversible vs reversible damage) in patients with ST-elevation myocardial infarction and non–ST-elevation myocardial infarction, and risk stratification and assessment of prognosis in patients with ACS. This review evaluates a potential clinical role of CMR in the acute setting, highlighting its advantages and limitations. This critical approach emphasizes areas of uncertainty and ongoing controversies but aims to equip the reader to evaluate the potential clinical application and the practicalities of CMR in patients presenting with ACS.     

Tirofiban therapy for patients with acute coronary syndromes and prior coronary artery bypass grafting in the PRISM-PLUS trial

The role of glycoprotein IIb/IIIa platelet receptor antagonist therapy for patients with an acute coronary syndrome (ACS) and a history of coronary artery bypass grafting (CABG) remains incompletely defined. We examined the outcomes of patients with an ACS and prior CABG who were treated with tirofiban versus placebo among subjects with prior CABG in the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) trial. Of 1,570 patients treated with tirofiban plus heparin (n = 773) or heparin alone (n = 797), 231 had prior CABG. Compared with patients without prior CABG, those with prior CABG were more likely to have risk factors for a complicated ACS course, including severe coronary artery disease and heart failure (all p <0.0001), typically had clinical predictors of benefit from tirofiban, such as ST-segment depression (p = 0.01) or a TIMI risk score >or=4 (p <0.001), and were more likely to die or have a myocardial infarction or refractory ischemia at all time points examined (p <0.0001). Among patients with prior CABG, decreases in the incidence of death, myocardial infarction, or refractory ischemia with tirofiban and heparin versus heparin alone were noted at 7 and 30 days (7 days: 16.9% vs 29.0%, p = 0.035; 30 days: 25.0% vs 40.2%, p = 0.015). Trends toward a decrease in death, myocardial infarction, and refractory ischemia with tirofiban and heparin versus heparin alone in the prior CABG subgroup were noted at 48 hours and 180 days (48 hours: 6.5% vs 14.0%, p = 0.09; 180 days: 37.1% vs 48.6%, p = 0.057). Bleeding rates were similar in patients with and without prior CABG. Tirofiban was well tolerated and tended to decrease the considerable risk for ischemic ACS complications in patients with prior CABG.     

Relationship between circulating endothelial cells and the predicted risk of cardiovascular events in acute coronary syndromes.

AIMS: The quantification of circulating endothelial cells (CECs) in whole blood is a novel marker of direct endothelial injury and shows promise as a potential biomarker of cardiovascular (CV) risk. The inter-relationship(s) between CECs and predicted CV risk has not been explored in large cohort of 'high-risk' patients. We hypothesized that there would be a significant relationship between increasing CEC counts and predicted CV risk in a broad spectrum of patients presenting with acute coronary syndrome (ACS). METHODS AND RESULTS: We studied 197 patients (aged 40-80 years) admitted with a confirmed diagnosis of unstable angina (UA), non-ST-elevation myocardial infarction (MI, NSTEMI), or ST-elevation MI (STEMI). CEC counts were performed on venous whole blood using the immunobead technique. Four well-validated ACS risk scores [(PURSUIT and TIMI for NSTEMI/UA) TIMI (STEMI) and GRACE (all ACS)] were calculated from the initial clinical history and electrocardiogram, as well as from values of laboratory parameters collected within 12 h of admission. We included a healthy control (HC) group of 50 matched patients in order to quantify the accuracy of CEC counts for the diagnosis of ACS and to compare disease vs. HC counts. CEC counts were significantly higher in the disease group when compared with the HC group. CEC counts significantly increased with increasing severity of disease (that is, UA vs. NSTEMI vs. STEMI; P = 0.002). CEC counts were higher among patients with clinical evidence of heart failure (Killip Class II-IV) when compared with those without (Killip Class I) on admission (P < 0.0001). There was a significant correlation between CEC counts and predicted CV risk for each of the four ACS risk scoring schemes (all P < 0.05). The area under the receiver-operating characteristic (ROC) curve (AUC) for the entire ACS cohort was 0.82 (95% CI: 0.76-0.88; P < 0.0001). A CEC count of >or=7/mL provided a positive predictive value of 90.6% (95% CI: 85.6-95.7%) and a negative predictive value of 53.5% (41.9-65.1%) for the diagnosis of MI (NSTEMI/STEMI) in the presence of an appropriate clinical presentation. CONCLUSION: There is a significant and positive correlation between increasing CECs and increasing CV risk in ACS. The diagnostic accuracy of CECs in this setting is only 'moderate'. Whilst it is good at confirming the presence of MI, a CEC value of <7.0/mL is less reliable at confidently excluding patients without disease.     

Benefits of pravastatin on cardiovascular events and mortality in older patients with coronary heart disease are equal to or exceed those seen in younger patients: Results from the LIPID trial

BACKGROUND: The effect of cholesterol-lowering therapy on death from coronary heart disease in older patients with previous coronary heart disease and average cholesterol levels is uncertain. OBJECTIVE: To compare the relative and absolute effects of pravastatin on cardiovascular disease outcomes in patients with coronary heart disease who are 65 years of age or older with those in patients 31 to 64 years of age. DESIGN: Subgroup analysis of a randomized, placebo-controlled trial. SETTING: 87 centers in Australia and New Zealand. PATIENTS: 3514 patients 65 to 75 years of age, chosen from among 9014 patients with previous myocardial infarction or unstable angina and a baseline plasma cholesterol level of 4.0 to 7.0 mmol/L (155 to 271 mg/dL). INTERVENTION: Pravastatin, 40 mg/d, or placebo. MEASUREMENTS: Major cardiovascular disease events over 6 years. RESULTS: Older patients were at greater risk than younger patients (31 to 64 years of age) for death (20.6% vs. 9.8%), myocardial infarction (11.4% vs. 9.5%), unstable angina (26.7% vs. 23.2%), and stroke (6.7% vs. 3.1%) (all P < 0.001). Pravastatin reduced the risk for all cardiovascular disease events, and similar relative effects were observed in older and younger patients. In patients 65 to 75 years of age, pravastatin therapy reduced mortality by 21% (CI, 7% to 32%), death from coronary heart disease by 24% (CI, 7% to 38%), coronary heart disease death or nonfatal myocardial infarction by 22% (CI, 9% to 34%), myocardial infarction by 26% (CI, 9% to 40%), and stroke by 12% (CI, -15% to 32%). For every 1000 older patients treated over 6 years, pravastatin prevented 45 deaths, 33 myocardial infarctions, 32 unstable angina events, 34 coronary revascularization procedures, 13 strokes, or 133 major cardiovascular events, compared with 22 deaths and 107 major cardiovascular events per 1000 younger patients. Among older patients, the numbers needed to treat were 22 (CI, 17 to 36) to prevent one death from any cause, 35 (CI, 24 to 67) to prevent one death from coronary heart disease, and 21 (CI, 17 to 31) to prevent one coronary heart disease death or nonfatal myocardial infarction. CONCLUSIONS: In older patients with coronary heart disease and average or moderately elevated cholesterol levels, pravastatin therapy reduced the risk for all major cardiovascular events and all-cause mortality. Since older patients are at greater risk than younger patients for these events, the absolute benefit of treatment is significantly greater in older patients.