Subject(s)
Atherosclerosis/complications , Fibrinolytic Agents/adverse effects , Secondary Prevention/methods , Vascular Diseases/pathology , Aspirin/adverse effects , Aspirin/therapeutic use , Chronic Disease , Clinical Trials as Topic , Death , Drug Therapy, Combination , Factor Xa Inhibitors/adverse effects , Factor Xa Inhibitors/therapeutic use , Fibrinolytic Agents/therapeutic use , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Humans , Myocardial Infarction/epidemiology , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/therapeutic use , Rivaroxaban/adverse effects , Rivaroxaban/therapeutic use , Stroke/epidemiology , Thrombosis/prevention & control , Vascular Diseases/prevention & controlABSTRACT
OBJECTIVES: A policy model is a model that can evaluate the effectiveness and cost-effectiveness of interventions and inform policy decisions. In this study, we introduce a cardiovascular disease (CVD) policy model which can be used to model remaining life expectancy including a measure of socioeconomic deprivation as an independent risk factor for CVD. DESIGN: A state transition model was developed using the Scottish Heart Health Extended Cohort (SHHEC) linked to Scottish morbidity and death records. Individuals start in a CVD-free state and can transit to three CVD event states plus a non-CVD death state. Individuals who have a non-fatal first event are then followed up until death. Taking a competing risk approach, the cause-specific hazards of a first event are modelled using parametric survival analysis. Survival following a first non-fatal event is also modelled parametrically. We assessed discrimination, validation and calibration of our model. RESULTS: Our model achieved a good level of discrimination in each component (c-statistics for men (women)-non-fatal coronary heart disease (CHD): 0.70 (0.74), non-fatal cerebrovascular disease (CBVD): 0.73 (0.76), fatal CVD: 0.77 (0.80), fatal non-CVD: 0.74 (0.72), survival after non-fatal CHD: 0.68 (0.67) and survival after non-fatal CBVD: 0.65 (0.66)). In general, our model predictions were comparable with observed event rates for a Scottish randomised statin trial population which has an overlapping follow-up period with SHHEC. After applying a calibration factor, our predictions of life expectancy closely match those published in recent national life tables. CONCLUSIONS: Our model can be used to estimate the impact of primary prevention interventions on life expectancy and can assess the impact of interventions on inequalities.
Subject(s)
Cardiovascular Diseases/epidemiology , Life Expectancy , Models, Cardiovascular , Primary Prevention/standards , Cardiovascular Diseases/economics , Cardiovascular Diseases/prevention & control , Cost-Benefit Analysis , Female , Humans , Male , Middle Aged , Morbidity/trends , Risk Factors , Socioeconomic Factors , Survival Rate/trends , United Kingdom/epidemiologyABSTRACT
Two once-daily rivaroxaban dosing regimens were compared with warfarin for stroke prevention in patients with non-valvular atrial fibrillation in ROCKET AF: 20 mg for patients with normal/mildly impaired renal function and 15 mg for patients with moderate renal impairment. Rivaroxaban population pharmacokinetic (PK)/pharmacodynamic (PD) modeling data from ROCKET AF patients (n = 161) are reported and are used to confirm established rivaroxaban PK and PK/PD models and to re-estimate values of the models' parameters for the current AF population. An oral one-compartment model with first-order absorption adequately described rivaroxaban PK. Age, renal function, and lean body mass influenced the PK model. Prothrombin time and prothrombinase-induced clotting time exhibited a near-linear relationship with rivaroxaban plasma concentration; inhibitory effects were observed through to 24 hours post-dose. Rivaroxaban plasma concentration and factor Xa activity had an inhibitory maximum-effect (Emax ) relationship. Renal function (on prothrombin time; prothrombinase-induced clotting time) and age (on factor Xa activity) had moderate effects on PK/PD models. PK and PK/PD models were shown to be adequate for describing the current dataset. These findings confirm the modeling and empirical results that led to the selection of doses tested against warfarin in ROCKET AF.
Subject(s)
Atrial Fibrillation/metabolism , Factor Xa Inhibitors , Models, Biological , Morpholines , Thiophenes , Aged , Aged, 80 and over , Blood Coagulation/drug effects , Double-Blind Method , Factor Xa/metabolism , Factor Xa Inhibitors/administration & dosage , Factor Xa Inhibitors/blood , Factor Xa Inhibitors/pharmacokinetics , Female , Humans , Male , Middle Aged , Morpholines/administration & dosage , Morpholines/blood , Morpholines/pharmacokinetics , Prothrombin Time , Renal Insufficiency/metabolism , Rivaroxaban , Thiophenes/administration & dosage , Thiophenes/blood , Thiophenes/pharmacokineticsABSTRACT
OBJECTIVE: To investigate temporal changes in survival after acute myocardial infarction (AMI) by early invasive strategy. METHODS: Accelerated failure time and 6-month relative survival analyses stratified by thrombolysis or primary percutaneous coronary intervention (PPCI) for ST elevation myocardial infarction (STEMI) and coronary angiography for non-STEMI (NSTEMI) encompassing 583 466 patients across 247 hospitals in England and Wales over hospital admission periods 2003-2004, 2005-2006, 2007-2008 and 2009-2010. RESULTS: Survival improved significantly for STEMI patients who received reperfusion therapy (time ratio (TR) 1.47, 95% CI 1.22 to 2.78) and was stable for those who did not (TR 1.02, 95% CI 0.85 to 1.22). While there were significant improvements in survival for NSTEMI patients who underwent coronary angiography (TR 1.39, 95% CI 1.18 to 1.62), there was a significant decline for those who did not (TR 0.70, 95% CI 0.65 to 0.75). Patients without reperfusion therapy or coronary angiography had a greater number of comorbidities, but the use of secondary prevention medications was comparable with patients who received reperfusion therapy or coronary angiography. There was a significant hospital-level survival effect, with higher crude 6-month mortality in hospitals in the lowest coronary angiography and PPCI quartiles (angiography Q1: 16.4% vs Q4: 12.8%; PPCI Q1: 15.8% vs Q4: 12.4%). CONCLUSIONS: Survival rates after AMI have improved. Whereas survival estimates for STEMI patients who did not receive reperfusion therapy were stable, they worsened for NSTEMI patients not receiving coronary angiography.
Subject(s)
Myocardial Infarction/mortality , Myocardial Infarction/therapy , Acute Disease , Adolescent , Adult , Aged , Aged, 80 and over , Female , Hospitalization , Humans , Male , Middle Aged , Outcome Assessment, Health Care , Percutaneous Coronary Intervention , Survival Analysis , Time Factors , Young AdultABSTRACT
BACKGROUND: Hospital acute myocardial infarction (AMI) care is increasingly evaluated using composite quality scores. We investigated the influence of three aggregation methods for an AMI indicator on mortality and hospital rank. METHODS AND RESULTS: We studied 136,392 patients discharged alive from 199 hospitals with AMI recorded in the Myocardial Ischaemia National Audit Project, between 01/01/2008 and 31/12/2009. A composite of prescription of aspirin, thienopyridine inhibitor, ß-blocker, angiotensin converting enzyme inhibitor, HMG CoA reductase enzyme inhibitor and enrolment in cardiac rehabilitation at discharge was aggregated as opportunity based (OBCS), weighted opportunity-based (WOBCS) and all-or-nothing (ANCS) scores. We quantified adjusted 30-day, 6-month and 1-year mortality rates and hospital performance rank. Median (IQR) scores were OBCS: 95.0% (3.5), WOBCS: 94.7% (0.8) and ANCS: 80.9% (11.8). The three methods affected the proportion of hospitals outside 99.8% credible limits of the national median (OBCS: 52.2%, WOBCS: 64.3% and ANCS: 37.7%) and hospital rank. Each 1% increase in composite score was significantly associated with a 1 to 3% and a 4% reduction in 6-month and 1-year mortality, respectively. However, the ANCS had fewer cases and no significant association with 30-day mortality. CONCLUSIONS: A hospital composite score, incorporating 6 aspects of AMI care, was significantly inversely associated with mortality. However, composite aggregation method influenced hospital rank, number of cases available for analysis and size of the association with all-cause mortality, with the ANCS performing least well. The use and choice of composite scores in hospital AMI quality improvement requires careful evaluation.
Subject(s)
Hospitalization , Medical Audit/standards , Myocardial Ischemia/diagnosis , Myocardial Ischemia/therapy , Quality Indicators, Health Care/standards , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Databases, Factual/standards , England/epidemiology , Female , Hospitalization/trends , Humans , Male , Medical Audit/trends , Middle Aged , Myocardial Ischemia/epidemiology , Quality Indicators, Health Care/trends , Wales/epidemiology , Young AdultABSTRACT
The innovative Spotlight of the Congress is "The heart interacting with systemic organs". For our patients, the interaction of cardiac conditions with other organs is fundamentally important to outcome, to safety and to clinical management. Related specialty areas have much to learn from each other and the ESC Congress 2013 will attract specialists from other organ systems to help understand disease mechanisms and improve the management of our patients.
ABSTRACT
BACKGROUND: Mortality rates after acute myocardial infarction (AMI) have declined, but there is uncertainty regarding the extent of improvements in early mortality in the elderly. METHODS: Mixed-effects regression analysis of 30-day mortality using data from 478,242 patients with AMI at 215 hospitals in England and Wales stratified by STEMI/NSTEMI, sex, and age group. A hospital opportunity-based composite score (OBCS) for aspirin, ACE-inhibitor, statin, ß blocker, and referral for cardiac rehabilitation was used as measure of quality of hospital care. RESULTS: 30-day mortality rates (95% CI) fell from 10.7% (10.6 to 10.9%) in 2004/5 to 8.4% (8.3 to 8.6%) in 2008/9. The median (IQR) hospital OBCSs increased over time, 2004/5: 87.3 (7.2), 2006/7: 88.9 (6.3), 2008/9: 90.3 (6.1), P<0.001, and were similar between age groups (18 to <65 years, 65 to 79 years, and ≥ 80 years) for STEMI: 89.4 (6.5) vs. 89.4 (6.6), vs. 89.2 (6.5) and NSTEMI: 88.6 (7.3) vs. 88.8 (7.0) vs. 88.9 (7.0), respectively For males, all age groups except patients <65 years demonstrated a significant decrease in adjusted mortality. For females, only patients ≥ 80 years demonstrated a significant reduction in adjusted mortality. A 1% increase in hospital OBCS was associated with a 1% decrease in 30-day mortality (95% CI: 0.99 to 0.99, P<0.001). CONCLUSION: In England and Wales, for patients with AMI there are age and sex-dependent differences in improvements in 30-day mortality. Whereas young males with AMI have reached an acceptable performance plateau, all other groups are either improving or, more importantly, are yet to demonstrate this.
Subject(s)
Hospital Mortality/trends , Medical Audit/trends , Myocardial Ischemia/diagnosis , Myocardial Ischemia/mortality , Registries , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , England/epidemiology , Female , Humans , Male , Middle Aged , Myocardial Infarction/diagnosis , Myocardial Infarction/mortality , Prospective Studies , Sex Factors , Time Factors , Wales/epidemiology , Young AdultABSTRACT
Beta-blockers are recommended as first-line symptomatic treatment for stable angina. However, their impact on mortality outside the context of myocardial infarction is unknown. We performed a meta-analysis of all randomized trials of beta-blockers in stable angina. Medical databases and cardiology journals were searched for relevant randomized clinical trials. The primary outcome was cardiovascular mortality, separately considering trials of beta-blockers versus placebo and beta-blockers versus other antianginals. We conducted a subgroup analysis on cardioselective versus non-cardioselective beta-blockers and calcium channel antagonists versus nitrates. We calculated odds ratios (ORs) and confidence intervals (CIs) using Peto's method. We found no statistically significant evidence that beta-blockers impact on mortality when compared with placebo (OR, 0.42; CI , 0.15-1.21) or other antianginals (OR, 0.98; CI, 0.86-1.10), or all others (OR, 0.97; CI, 0.86-1.09). There was a trend for cardioselective beta-blockers to have a greater improvement in mortality when compared with placebo and to have greater impact than non-calcium channel antagonists. Beta-blockers do not have statistically significant impact on mortality versus placebo or versus other active comparators. The findings exclude a benefit of 15% or greater and a hazard of 10% or greater. The impact of cardioselectivity requires further study.
Subject(s)
Angina, Stable/drug therapy , Antihypertensive Agents/pharmacology , Calcium Channel Blockers/pharmacology , Myocardial Infarction/prevention & control , Angina, Stable/mortality , Antihypertensive Agents/administration & dosage , Calcium Channel Blockers/administration & dosage , Female , Humans , Male , Myocardial Infarction/drug therapy , Myocardial Infarction/mortality , Randomized Controlled Trials as TopicABSTRACT
BACKGROUND: Many markers of platelet activation have been described but their reproducibility and comparability in patient populations are poorly defined. OBJECTIVES: We sought to compare markers of platelet and monocyte activation with platelet-monocyte aggregates, a proposed gold standard of in vivo platelet activation, and assess their reproducibility in patients with peripheral arterial disease: a population with substantial platelet activation, inflammation and risk of thrombotic events. PATIENTS/METHODS: Thirty patients with peripheral vascular disease attended on two occasions to permit within-day and between-day comparisons. In vivo platelet and monocyte activation were determined by flow-cytometric quantification of platelet-monocyte aggregation, platelet surface expression of P-selectin and CD40L, platelet-derived microparticles, and monocyte surface expression of CD40 and CD11b. Plasma concentrations of platelet-derived microparticles, soluble P-selectin and CD40L were measured by enzyme-linked immunosorbant assays. RESULTS: Platelet-monocyte aggregation (36.7±7.86%), and platelet surface expression of P-selectin (5.8±1.65%) and CD40L (3.3±1.45%) demonstrated comparable within-day (mean difference±co-efficient of reproducibility; 0.9±15.4%, 0.21±1.65% and 0.2±2.8% respectively) and between-day reproducibility (2.0±12.4%, 0.10±2.25% and 0.9±6.4% respectively). Platelet-monocyte aggregates correlated well with other platelet (r=0.30-0.50, P<0.02) and monocyte (r=0.27-0.47, P<0.03) activation markers. Flow cytometric and assay quantified platelet-derived microparticles showed poorer reproducibility (co-efficient of reproducibility >40). CONCLUSIONS: In patients with peripheral arterial disease, measurements of platelet-monocyte aggregates have good reproducibility and consistently reflect other markers of platelet and monocyte activation.
Subject(s)
Biomarkers/blood , Peripheral Vascular Diseases/blood , Platelet Activation , Platelet Function Tests , CD11b Antigen/blood , CD40 Antigens/blood , CD40 Ligand/blood , Cell-Derived Microparticles/metabolism , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Humans , Male , Middle Aged , Monocytes/immunology , Monocytes/metabolism , Observer Variation , P-Selectin/blood , Peripheral Vascular Diseases/diagnosis , Peripheral Vascular Diseases/immunology , Platelet Adhesiveness , Predictive Value of Tests , Prognosis , Reproducibility of Results , ScotlandABSTRACT
AIMS: To examine age-dependent in-hospital mortality for hospitalization with acute coronary syndromes (ACS) in England and Wales. METHODS AND RESULTS: Mixed-effects regression analysis using data from 616 011 ACS events at 255 hospitals as recorded in the Myocardial Ischemia National Audit Project (MINAP) 2003-2010; 102 415 (16.7%) patients were aged <55 years and 72 721 (11.9%) ≥85 years. Patients ≥85 years with ST-elevation myocardial infarction (STEMI) were less likely to receive emergency reperfusion therapy than those <55 years (RR = 0.27, 95% CI: 0.25-0.28). Older patients had greater lengths of stay (P< 0.001) and higher in-hospital mortality (P< 0.001). For STEMI and non-ST-elevation myocardial infarction (NSTEMI), there were reductions in in-hospital mortality from 2003 to 2010 across all age groups including the very elderly. For STEMI ≥ 85 years, in-hospital mortality reduced from 30.1% in 2003 to 19.4% in 2010 (RR = 0.54, 95% CI: 0.38-0.75, P< 0.001), and for NSTEMI ≥ 85 years, from 31.5% in 2003 to 20.4% in 2010 (RR = 0.56, 95% CI: 0.42-0.73, P< 0.001). Findings were upheld after multi-level adjustment (base = 2003): male STEMI 2010 OR = 0.60, 95% CI: 0.48-0.75; female STEMI 2010 OR = 0.55, 95% CI: 0.42-0.71; male NSTEMI OR = 0.50, 95% CI: 0.42-0.60; female NSTEMI OR = 0.49, 95% CI: 0.40-0.59. CONCLUSION: For patients hospitalized with ACS in England and Wales, there have been substantial reductions in in-hospital mortality rates from 2003 to 2010 across all age groups. The temporal improvements in mortality were similar for sex and type of acute myocardial infarction. Age-dependent inequalities in the management of ACS were apparent.
Subject(s)
Acute Coronary Syndrome/mortality , Myocardial Infarction/mortality , Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/therapy , Adult , Age Distribution , Aged , Aged, 80 and over , Angioplasty, Balloon, Coronary/mortality , Angioplasty, Balloon, Coronary/statistics & numerical data , England , Female , Healthcare Disparities/statistics & numerical data , Hospital Mortality , Humans , Length of Stay , Male , Medical Audit , Middle Aged , Myocardial Infarction/diagnosis , Myocardial Infarction/therapy , Retrospective Studies , Risk Factors , Thrombolytic Therapy/mortality , Thrombolytic Therapy/statistics & numerical data , WalesABSTRACT
The aim of GRACE was to provide a large multinational registry of the full spectrum of patients with acute coronary syndromes (ACS) in order to define patient characteristics and outcomes and derive predictive risk scores. The study was designed and administered by an independent steering committee; data analyses were performed under the guidance of the steering committee at the Center for Outcomes Research of the University of Massachusetts. Regular feedback regarding local, regional and international guideline and performance measures was provided to individual hospitals and clusters of hospitals. Regional and international benchmark data were available to all sites. Main GRACE involved 123 hospitals in 14 countries in North and South America, Europe, Australia and New Zealand. GRACE2 (Expanded GRACE) comprised 154 hospitals in Europe, North and South America, Asia, Australasia and China. Continuous recruitment and follow-up took place between 1999 and 2009. The first 10 -20 patients per site (depending on hospital size) were enrolled each month, resulting in the recruitment of 102 341 patients, who were categorized as having ST-segment elevation myocardial infarction, non-ST-elevation myocardial infarction or unstable angina. Standardized case report forms (datafax or electronic) were completed by trained study coordinators, and included fields relating to demographic factors, comorbid conditions, treatments and in-hospital and post-discharge (6-month) events. Blood sampling, genetic analyses and longer-term follow-up were undertaken in GRACE substudies. Prospective individual patient follow-up was carried out. All sites were audited locally; 10% of individual patient records were audited in a 2-year cycle. Less than 1% of 20 key baseline fields, and less than 1% of discharge diagnosis and discharge status data, were missing. Six-month follow-up was 85% complete. Publications and risk scores are available at http://www.outcome.org/grace. Proposals for specific analyses were considered, in competition, by an independent publications committee.
Subject(s)
Acute Coronary Syndrome/epidemiology , International Cooperation , Registries , Acute Coronary Syndrome/etiology , Acute Coronary Syndrome/therapy , Humans , Quality of Health Care , Registries/standards , Risk Assessment/methods , Treatment OutcomeABSTRACT
BACKGROUND: The principal inhibitor of fibrinolysis in vivo is plasminogen activator inhibitor-1 (PAI-1). PAI-749 is a small molecule inhibitor of PAI-1 with proven antithrombotic efficacy in several preclinical models. OBJECTIVE: To assess the effect of PAI-749, by using an established ex vivo clinical model of thrombosis and a range of complementary in vitro human plasma-based and whole blood-based models of fibrinolysis. METHODS: In a double-blind, randomized, crossover study, ex vivo thrombus formation was assessed using the Badimon chamber in 12 healthy volunteers during extracorporeal administration of tissue-type plasminogen activator (t-PA) in the presence of PAI-749 or control. t-PA-mediated lysis of plasma clots and of whole blood model thrombi were assessed in vitro. The role of vitronectin was examined by assessing lysis of fibrin clots generated from purified plasma proteins. RESULTS: There was a dose-dependent reduction in ex vivo thrombus formation by t-PA (P < 0.0001). PAI-749 had no effect on in vitro or ex vivo thrombus formation or fibrinolysis in the presence or absence of t-PA. Inhibition of PAI-1 with a blocking antibody enhanced fibrinolysis in vitro (P < 0.05). CONCLUSIONS: Despite its efficacy in a purified human system and in preclinical models of thrombosis, the current study suggests that PAI-749 does not affect thrombus formation or fibrinolysis in a range of established human plasma and whole blood-based systems.
Subject(s)
Fibrinolysis/drug effects , Indoles/pharmacology , Plasminogen Activator Inhibitor 1 , Tetrazoles/pharmacology , Adult , Cross-Over Studies , Double-Blind Method , Humans , Models, BiologicalABSTRACT
BACKGROUND: In the OASIS-5 trial, fondaparinux reduced major bleeding with similar short-term efficacy as enoxaparin but lowered death and stroke during long-term follow-up. The mechanism of lower bleeding and improved efficacy with fondaparinux is uncertain. METHODS AND RESULTS: We compared the anti-Xa concentration (reflecting drug levels), Xa clot time (reflecting anticoagulant effect) and endogenous thrombin potential (ETP; a global test of hemostatic function) in plasma samples collected 6, 24 and 72 h after the first dose of the study drug in 48 patients randomly assigned fondaparinux 2.5 mg day(-1) and 42 patients assigned enoxaparin 1 mg kg(-1) twice daily in the OASIS-5 trial. Patients assigned to fondaparinux compared with enoxaparin had a significantly lower mean anti-Xa level [0.52 IU mL(-1) (SD 0.22 IU mL(-1)) vs. 1.2 IU mL(-1) (SD 0.45 IU mL(-1)), P<0.0001] and Xa clot time [64.9 s (SD 17.7 s) vs. 111.8 s (SD 29.6 s), P<0.0001], and significantly higher ETP area under the curve (AUC) [386.7 mA (SD 51.5 mA) vs. 206.4 mA (SD 90.6 mA), P<0.001] at 6 h, and these differences remained evident at 24 and 72 h. There was significantly less variability of the results of anti-Xa levels, Xa clot time and ETP AUC for fondaparinux compared with enoxaparin at 6 h (P<0.001 for each comparison). CONCLUSION: Fondaparinux 2.5 mg day(-1) compared with enoxaparin 1 mg kg(-1) twice daily produces less variable anticoagulant effect and lower mean anticoagulant intensity. These results most likely explain the reduced risk of bleeding seen with fondaparinux compared with enoxaparin in the OASIS-5 trial and suggest that a lower intensity of anticoagulation than used in the past may be sufficient to prevent recurrent ischemic events and death in patients with ACS who are concurrently treated with aspirin and clopidogrel.
Subject(s)
Acute Coronary Syndrome/drug therapy , Anticoagulants/administration & dosage , Blood Coagulation/drug effects , Enoxaparin/administration & dosage , Polysaccharides/administration & dosage , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/mortality , Aged , Anticoagulants/adverse effects , Dose-Response Relationship, Drug , Double-Blind Method , Drug Monitoring/methods , Enoxaparin/adverse effects , Factor Xa Inhibitors , Fondaparinux , Hemorrhage/chemically induced , Humans , Injections, Subcutaneous , Middle Aged , Partial Thromboplastin Time , Platelet Aggregation Inhibitors/therapeutic use , Polysaccharides/adverse effects , Risk Assessment , Risk Factors , Secondary Prevention , Thrombin/metabolism , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Interaction of P-selectin with its glycoprotein ligand (P-selectin glycoprotein ligand type 1) mediates inflammatory processes that may also include vascular thrombosis. Platelet P-selectin expression is increased in patients with coronary heart disease, and its antagonism represents a potential future therapeutic target for the prevention and treatment of atherothrombosis. AIM: To investigate the effects of the novel small molecule P-selectin antagonist PSI-697 on thrombus formation in humans. METHODS AND RESULTS: In a double-blind randomized crossover study, thrombus formation was measured in 12 healthy volunteers, using the Badimon ex vivo perfusion chamber under conditions of low and high shear stress. Saline placebo, low-dose (2 m) and high-dose (20 m) PSI-697 and the glycoprotein IIb-IIIa receptor antagonist tirofiban (50 ng mL(-1)) were administered into the extracorporeal circuit prior to the perfusion chamber. As compared with saline placebo, blockade of platelet glycoprotein IIb-IIIa receptor with tirofiban produced 28% and 56% reductions in thrombus formation in the low-shear and high-shear chambers, respectively. PSI-697 caused a dose-dependent, but more modest, reduction in thrombus formation. Low-dose PSI-796 (2 m) reduced total thrombus area by 14% (P = 0.04) and 30% (P = 0.0002) in the low-shear and high-shear chambers, respectively. At the high dose (20 m), PSI-697 reduced total thrombus area by 18% (P = 0.0094) and 41% (P = 0.0008) in the low-shear and high-shear chambers, respectively. CONCLUSIONS: P-selectin antagonism with PSI-697 reduces ex vivo thrombus formation in humans. These findings provide further evidence that P-selectin antagonism may be a potential target for the prevention and treatment of cardiovascular disease.
Subject(s)
P-Selectin/antagonists & inhibitors , Thrombosis/prevention & control , Adolescent , Adult , Blood/drug effects , Cells, Cultured , Cross-Over Studies , Double-Blind Method , Humans , Hydroxyquinolines/pharmacology , Perfusion , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Thrombosis/drug therapy , Tirofiban , Tyrosine/analogs & derivatives , Tyrosine/pharmacology , Young AdultABSTRACT
BACKGROUND: Abdominal obesity is known to be a risk factor for cardiovascular and metabolic diseases. However, despite the importance of abdominal obesity as a risk factor for cardiovascular and metabolic disease, there are currently no UK-specific data on its prevalence in patients attending primary care. AIM: The aim of the International Day for the Evaluation of Abdominal obesity (IDEA)-UK observational study was to determine the distribution of waist circumference--a marker of abdominal obesity--and its relationship with cardiovascular risk markers in a UK-based primary care population. METHODS: Patients underwent measurements of height, weight and waist circumference and provided data on reported cardiovascular disease (CVD), diabetes, hypertension and dyslipidaemia. RESULTS: A total of 1731 patients were assessed within the study, of which 719 were male and 1012 were female. Of these 1731 patients, 1718 had complete datasets for the presence of reported cardiovascular risk factors. Median waist circumference in the male and female populations respectively was 99.0 cm [interquartile range (IQR) 91.0-108.0 cm] and 89.0 cm (IQR 79.0-100 cm). In all, 38.8% of men and 51.2% of women were abdominally obese (waist circumference > 102 cm and > 88 cm respectively) according to the US National Cholesterol Education Program (NCEP) guidelines. Within both male and female populations, the incidence of reported CVD, lipid disorders, hypertension and diabetes increased with increasing quartiles for waist circumference. CONCLUSION: Increased waist circumference is widespread in patients attending primary care in the UK and is associated with elevated levels of reported diabetes, hypertension, lipid disorders and CVD.
Subject(s)
Obesity, Abdominal/etiology , Adolescent , Adult , Aged , Aged, 80 and over , Cardiovascular Diseases/epidemiology , Diabetes Mellitus/epidemiology , Dyslipidemias/epidemiology , Female , Humans , Hypertension/epidemiology , Male , Middle Aged , Prevalence , Risk Factors , United Kingdom/epidemiology , Waist Circumference , Young AdultABSTRACT
OBJECTIVE: To identify patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) with a low likelihood of any adverse in-hospital event. DESIGN, SETTING AND PATIENTS: Data were analysed from 24 097 patients with NSTEMI or unstable angina included in the Global Registry of Acute Coronary Events (January 2001 to September 2007). MAIN OUTCOME MEASURES: In-hospital events were myocardial infarction, arrhythmia, congestive heart failure or shock, major bleeding, stroke or death. Two-thirds of the patients were randomly chosen for model development and the remainder for model validation. Multiple logistic regression identified predictors of freedom from an in-hospital event, and a Freedom-from-Event score was developed. RESULTS: Of the 16 127 patients in the model development group, 19.1% experienced an in-hospital adverse event. Fifteen factors independently predicted freedom from an adverse event: younger age; lower Killip class; unstable angina presentation; no hypotension; no ST deviation; no cardiac arrest at presentation; normal creatinine; decreased pulse rate; no hospital transfer; no history of diabetes, heart failure, peripheral arterial disease, or atrial fibrillation; prehospital use of statins, and no chronic warfarin. In the validation group, 18.6% experienced an adverse event. The model discriminated well between patients experiencing an in-hospital event and those who did not in both derivation and validation groups (c-statistic = 0.77 in both). Patients in the three lowest risk deciles had a very low in-hospital mortality (<0.5%) and an uncomplicated clinical course (>93% event-free in hospital). The model also predicted freedom from postdischarge events (death, myocardial infarction, stroke; c-statistic = 0.77). CONCLUSIONS: The GRACE Freedom-from-Event score can predict the in-hospital course of NSTE-ACS, and identifies up to 30% of the admitted population at low risk of death or any adverse in-hospital event.
Subject(s)
Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/complications , Acute Coronary Syndrome/epidemiology , Adult , Age Factors , Aged , Aged, 80 and over , Arrhythmias, Cardiac/epidemiology , Electrocardiography , Epidemiologic Methods , Female , Heart Failure/epidemiology , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Myocardial Infarction/epidemiology , PrognosisABSTRACT
BACKGROUND: Evidence suggests that an early interventional strategy for patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) can improve health outcomes but also increase costs when compared with a conservative strategy. OBJECTIVE: The aim of this study was to assess the cost-effectiveness of an early interventional strategy in different risk groups from a UK health-service perspective. DESIGN: Decision-analytic model based on randomised clinical trial data. MAIN OUTCOME MEASURES: Costs in UK Sterling at 2003/2004 prices and quality-adjusted life years (QALYs) combined into an incremental cost-effectiveness ratio. METHODS: Data from the third Randomised Intervention Trial of unstable Angina (RITA 3) was employed to estimate rates of cardiovascular death and myocardial infarction, costs and health-related quality of life. Cost-effectiveness was estimated over patients' lifetimes within the decision-analytic model. RESULTS: The mean incremental cost per QALY gained for an early interventional strategy was approximately 55,000 pounds sterling, 22,000 pounds sterling and 12,000 pounds sterling for patients at low, intermediate and high risk, respectively. The early interventional strategy is approximately 1%, 35% and 95% likely to be cost-effective for patients at low, intermediate and high risk, respectively, at a threshold of 20,000 pounds sterling per QALY. The cost-effectiveness of early intervention in low-risk patients is sensitive to assumptions about the duration of the treatment effect. CONCLUSION: An early interventional strategy in patients presenting with NSTE-ACS is likely to be considered cost-effective for patients at high and intermediate risk, but this is less likely to be the case for patients at low risk.
Subject(s)
Acute Coronary Syndrome/economics , Coronary Angiography/economics , Quality-Adjusted Life Years , Acute Coronary Syndrome/mortality , Acute Coronary Syndrome/therapy , Aged , Aged, 80 and over , Angina, Unstable/economics , Angina, Unstable/therapy , Cost-Benefit Analysis/economics , Costs and Cost Analysis , Diabetic Angiopathies/therapy , Female , Humans , Male , Middle Aged , Multicenter Studies as Topic , Proportional Hazards Models , Randomized Controlled Trials as TopicABSTRACT
OBJECTIVE: To compare the characteristics, management, and outcomes of patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) who would have been eligible for inclusion in clinical trials of glycoprotein (GP) IIb/IIIa inhibitors with those of ineligible patients. DESIGN: Multinational, prospective, observational study (GRACE, Global Registry of Acute Coronary Events). SETTING: Patients hospitalised for a suspected acute coronary syndrome and enrolled in GRACE between April 1999 and December 2004. PATIENTS: 29 039 patients with NSTE ACS. MAIN OUTCOME MEASURES: Characteristics and outcomes were compared for trial-eligible (75.0%) and trial-ineligible (25.0%) patients. RESULTS: GP IIb/IIIa inhibitors were administered to 20.0% of eligible and 15.3% of ineligible patients. Compared with eligible patients, ineligible patients who received GP IIb/IIIa inhibitors had significantly higher rates of hospital death (6.8% vs 3.7%) and major bleeding (4.9% vs 2.2%). After adjustment for their higher baseline risk, ineligible patients still experienced higher hospital death rates (adjusted odds ratio (OR) 1.60; 95% confidence interval (CI) 1.01 to 2.39), but not higher bleeding rates, than the eligible group. Use of GP IIb/IIIa inhibitors was associated with a trend towards lower 6-month mortality in eligible (OR 0.86, 95% CI 0.72 to 1.02) and ineligible (OR 0.82, 95% CI 0.65 to 1.05) patients compared with those in whom this therapy was not used. CONCLUSIONS: GP IIb/IIIa inhibitors were markedly underused in the real-world population, irrespective of whether patients were trial-eligible or not. Despite the higher risk of ineligible patients, the benefits of GP IIb/IIIa inhibitors appear to be no less than in eligible patients.
Subject(s)
Acute Coronary Syndrome/drug therapy , Myocardial Infarction/drug therapy , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Acute Coronary Syndrome/mortality , Aged , Cohort Studies , Death, Sudden, Cardiac/etiology , Female , Hemorrhage/etiology , Hemorrhage/mortality , Hospitalization , Humans , Male , Middle Aged , Myocardial Infarction/mortality , Prospective Studies , Risk Factors , Stroke/etiology , Stroke/mortality , Treatment OutcomeABSTRACT
BACKGROUND: Accurate risk stratification soon after admission for patients with acute coronary syndromes (ACS) is vital in guiding management. Clinical risk scores and B-type natriuretic peptide (BNP) can predict mortality and re-infarction in ACS, but it is unknown whether BNP provides prognostic information over and above that of the clinical risk scores. METHODS: 142 unselected patients with ACS were prospectively studied. BNP was measured and patients were stratified according to BNP and Global Registry of Acute Coronary Events (GRACE) score. In-hospital and 30-day events were characterised. RESULTS: 20.4% of ACS subjects had ST-elevation myocardial infarction (MI), 14.1%, non-ST elevation MI and 65.5% unstable angina. Elevated BNP predicted in-hospital and 30-day heart failure (p<0.01), and the risk of in-hospital recurrent ACS (p<0.05). Increasing GRACE score predicted in-hospital recurrent ACS (p<0.05), heart failure (p<0.001), arrhythmias (p<0.05) and angioplasty (p<0.05). GRACE score also predicted 30-day heart failure (p<0.05). In contrast, the predictive accuracy of troponin elevation was less robust. CONCLUSION: BNP and the GRACE score predict complementary outcomes from ACS, but both predicted heart failure. BNP is a powerful indicator of heart failure in patients with ACS and provides prognostic information above and beyond conventional biomarkers and risk scores.
Subject(s)
Coronary Disease/diagnosis , Natriuretic Peptide, Brain/blood , Aged , Angina, Unstable/diagnosis , Coronary Disease/blood , Coronary Disease/mortality , Female , Humans , Male , Myocardial Infarction/diagnosis , Prognosis , Prospective StudiesABSTRACT
OBJECTIVE: Treatment delays may result in different clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) who receive fibrinolytic therapy vs primary percutaneous coronary intervention (PCI). The aim of this analysis was to examine how treatment delays relate to 6-month mortality in reperfusion-treated patients enrolled in the Global Registry of Acute Coronary Events (GRACE). DESIGN: Prospective, observational cohort study. SETTING: 106 hospitals in 14 countries. PATIENTS: 3959 patients who presented with STEMI within 6 h of symptom onset and received reperfusion with either a fibrin-specific fibrinolytic drug or primary PCI. MAIN OUTCOME MEASURES: 6-month mortality. METHODS: Multivariable logistic regression was used to assess the relationship between outcomes and treatment delay separately in each cohort, with time modelled with a quadratic term after adjusting for covariates from the GRACE risk score. RESULTS: A total of 1786 (45.1%) patients received fibrinolytic therapy, and 2173 (54.9%) underwent primary PCI. After multivariable adjustment, longer treatment delays were associated with a higher 6-month mortality in both fibrinolytic therapy and primary PCI patients (p<0.001 for both cohorts). For patients who received fibrinolytic therapy, 6-month mortality increased by 0.30% per 10-min delay in door-to-needle time between 30 and 60 min compared with 0.18% per 10-min delay in door-to-balloon time between 90 and 150 min for patients undergoing primary PCI. CONCLUSIONS: Treatment delays in reperfusion therapy are associated with higher 6-month mortality, but this relationship may be even more critical in patients receiving fibrinolytic therapy.