ABSTRACT
INTRODUCTION: Inclisiran, an siRNA targeting hepatic PCSK9 mRNA, administered twice-yearly (after initial and 3-month doses), substantially and sustainably reduced LDL-cholesterol (LDL-C) in Phase III trials. Whether lowering LDL-C with inclisiran translates into a reduced risk of major adverse cardiovascular events (MACE) is not yet established. In-silico trials applying a disease computational model to virtual patients receiving new treatments allow to emulate large scale long term clinical trials. The SIRIUS in-silico trial programme aims to predict the efficacy of inclisiran on CV events in individuals with established atherosclerotic cardiovascular disease (ASCVD). METHODS: A knowledge-based mechanistic model of ASCVD was built, calibrated, and validated to conduct the SIRIUS programme (NCT05974345) aiming to predict the effect of inclisiran on CV outcomes.The SIRIUS Virtual Population included patients with established ASCVD (previous myocardial infarction (MI), previous ischemic stroke (IS), previous symptomatic lower limb peripheral arterial disease (PAD) defined as either intermittent claudication with ankle-brachial index <0.85, prior peripheral arterial revascularization procedure, or vascular amputation) and fasting LDL-C ≥ 70 mg/dL, despite stable (≥ 4 weeks) well-tolerated lipid lowering therapies.SIRIUS is an in-silico multi-arm trial programme. It follows an idealized crossover design where each virtual patient is its own control, comparing inclisiran to 1) placebo as adjunct to high-intensity statin therapy with or without ezetimibe, 2) ezetimibe as adjunct to high-intensity statin therapy, 3) evolocumab as adjunct to high-intensity statin therapy and ezetimibe.The co-primary efficacy outcomes are based on time to the first occurrence of any component of 3P-MACE (composite of CV death, nonfatal MI or nonfatal IS) and time to occurrence of CV death over 5 years. PERSPECTIVES/CONCLUSION: The SIRIUS in-silico trial programme will provide early insights regarding a potential effect of inclisiran on MACE in ASCVD patients, several years before the availability of the results from ongoing CV outcomes trials (ORION-4 and VICTORION-2-P).
The SIRIUS in-silico trial programme is a knowledge-based computer model built to simulate the biological and clinical long-term effects of inclisiran, an siRNA targeting hepatic PCSK9 mRNA, on virtual patients with cardiovascular disease. Key Findings: The model accurately replicates the biological processes of cardiovascular disease and the impact of lipid-lowering therapies, allowing for the prediction of randomized clinical trials.Simulating clinical trials with virtual patients can provide insights into the efficacy and safety of new treatments before the results of randomized clinical trials, potentially speeding up the drug development process.
ABSTRACT
BACKGROUND: Existing cardiovascular risk scores for patients with established cardiovascular disease (CVD) estimate residual risk of recurrent major cardiovascular events (MACE). The aim of the current study is to develop and externally validate a prediction model to estimate the 10-year combined risk of recurrent MACE and cardiovascular interventions (MACE+) in patients with established CVD. METHODS: Data of patients with established CVD from the UCC-SMART cohort (N = 8421) were used for model development, and patient data from REACH Western Europe (N = 14,528) and REACH North America (N = 19,495) for model validation. Predictors were selected based on the existing SMART risk score. A Fine and Gray competing risk-adjusted 10-year risk model was developed for the combined outcome MACE+. The model was validated in all patients and in strata of coronary heart disease (CHD), cerebrovascular disease (CeVD), peripheral artery disease (PAD). RESULTS: External calibration for 2-year risk in REACH Western Europe and REACH North America was good, c-statistics were moderate: 0.60 and 0.58, respectively. In strata of CVD at baseline good external calibration was observed in patients with CHD and CeVD, however, poor calibration was seen in patients with PAD. C-statistics for patients with CHD were 0.60 and 0.57, for patients with CeVD 0.62 and 0.61, and for patients with PAD 0.53 and 0.54 in REACH Western Europe and REACH North America, respectively. CONCLUSIONS: The 10-year combined risk of recurrent MACE and cardiovascular interventions can be estimated in patients with established CHD or CeVD. However, cardiovascular interventions in patients with PAD could not be predicted reliably.
Subject(s)
Cardiovascular Diseases , Cerebrovascular Disorders , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/therapy , Europe/epidemiology , Humans , North America/epidemiology , Risk Assessment , Risk FactorsABSTRACT
BACKGROUND: Following the publication of the COMPASS trial, the European Medicines Agency has approved a regimen of combination of rivaroxaban 2.5mg twice daily and a daily dose of 75-100mg acetylsalicylic acid (ASA) for patients with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) at high risk of ischemic events. However, the applicability of such a therapeutic strategy in France is currently unknown. AIMS: To describe the proportion of patients eligible to COMPASS in France, their baseline clinical characteristics and the rate of major adverse cardiovascular events, using the REACH registry. METHODS: From the the REduction of Atherothrombosis for Continued Health (REACH) registry database, a large international registry of patients with, or at risk, of atherothrombosis, we analyzed patients included in France with either established CAD and/or PAD and fulfilling the inclusion and exclusion criteria of the COMPASS trial. The ischemic outcome was a composite of cardiovascular (CV) death, myocardial infarction (MI), or stroke, and serious bleeding were defined as haemorrhagic stroke or bleeding leading to hospitalization or transfusion. RESULTS: Among more than 65000 patients enrolled in REACH, 2.012 patients were evaluable and enrolled in France. Among them, 1194 patients (59.3%) were eligible to COMPASS. The main reasons for exclusion of the COMPASS trial, were high bleeding risk (59.1%), anticoagulant use (43.4%), requirement for dual antiplatelet therapy within 1 year of an ACS or PCI (24.7%). In the "COMPASS eligible population", the rate of MACE (CV, MI and stroke) at 4 years follow-up was 13.4% [11.3-15.8], and serious bleeding was 2.5% at 4 years [1.6-3.4]. Patients with polyvascular disease (n=219) had the highest rate of MACE, compared with patients with CAD only and PAD only (19.1% [13.9-26.1] vs. 11.6% [9.1-14.8] vs 13.2% [9.2-18.8], P<0.0001, respectively). CONCLUSION: The COMPASS therapeutic strategy in France appears to be applicable to more than half of CAD or PAD patients. This population appears at high residual risk of atherothrombotic events, and patients with polyvascular disease experienced the highest rate of events.
Subject(s)
Anticoagulants/administration & dosage , Aspirin/administration & dosage , Coronary Artery Disease/drug therapy , Peripheral Arterial Disease/drug therapy , Platelet Aggregation Inhibitors/administration & dosage , Rivaroxaban/administration & dosage , Aged , Analysis of Variance , Atherosclerosis , Coronary Artery Disease/epidemiology , Drug Administration Schedule , Female , Follow-Up Studies , France/epidemiology , Hemorrhage/etiology , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Myocardial Infarction/epidemiology , Patient Selection , Percutaneous Coronary Intervention , Peripheral Arterial Disease/epidemiology , Prospective Studies , Registries/statistics & numerical data , Risk Factors , Stroke/epidemiology , Thrombosis/etiology , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: The benefits and risks of blood transfusion in patients with acute myocardial infarction who are anemic or who experience bleeding are debated. We sought to study the association between blood transfusion and ischemic outcomes according to haemoglobin nadir and bleeding status in patients with NST-elevation myocardial infarction (NSTEMI). METHODS: The TAO trial randomized patients with NSTEMI and coronary angiogram scheduled within 72h to heparin plus eptifibatide versus otamixaban. After exclusion of patients who underwent coronary artery bypass surgery, patients were categorized according to transfusion status considering transfusion as a time-varying covariate. The primary ischemic outcome was the composite of all-cause death or MI within 180 days of randomization. Subgroup analyses were performed according to pre-transfusion hemoglobin nadir and bleeding status. RESULTS: 12,547 patients were enrolled. Among these, blood transfusion was used in 489 (3.9%) patients. Patients who received transfusion had a higher rate of death or MI (29.9% vs. 8.1%, p<0.01). This excess risk persisted after adjustment on GRACE score and nadir of hemoglobin (HR 3.36 95%CI 2.63-4.29 p<0.01). Subgroup analyses showed that blood transfusion was associated with a higher risk in patients without overt bleeding (adjusted HR 6.25 vs. 2.85; p-interaction 0.001) as well as in those with hemoglobin nadir > 9.0 g/dl (HR 4.01; p-interaction<0.0001). CONCLUSION: In patients with NSTEMI, blood transfusion was associated with an overall increased risk of ischaemic events. However, this was mainly driven by patients without overt bleeding and those hemoglobin nadir > 9.0g/dl. This suggests possible harm of transfusion in those groups.
Subject(s)
Acute Coronary Syndrome , Anemia , Percutaneous Coronary Intervention , Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/therapy , Anemia/diagnosis , Anemia/epidemiology , Anemia/therapy , Blood Transfusion , Eptifibatide , Hemorrhage/chemically induced , Hemorrhage/diagnosis , Hemorrhage/epidemiology , Humans , Treatment OutcomeSubject(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
BACKGROUND: Randomized controlled trials (RCTs) on pediatric venous thromboembolism (VTE) treatment have been challenged by unsubstantiated design assumptions and/or poor accrual. Pilot/feasibility (P/F) studies are critical to future RCT success. METHODS: The Kids-DOTT trial is a multicenter RCT investigating non-inferiority of a 6-week (shortened) versus 3-month (conventional) duration of anticoagulation in patients aged < 21 years with provoked venous thrombosis. Primary efficacy and safety endpoints are symptomatic recurrent VTE at 1 year and anticoagulant-related, clinically relevant bleeding. In the P/F phase, 100 participants were enrolled in an open, blinded-endpoint, parallel-cohort RCT design. RESULTS: No eligibility violations or randomization errors occurred. Of the enrolled patients, 69% were randomized, 3% missed the randomization window, and 28% were followed in prespecified observational cohorts for completely occlusive thrombosis or persistent antiphospholipid antibodies. Retention at 1 year was 82%. Interobserver agreement between local and blinded central determination of venous occlusion by imaging at 6 weeks after diagnosis was strong (k-statistic = 0.75; 95% confidence interval [CI] 0.48-1.0). The primary efficacy and safety event rates were 3.3% (95% CI 0.3-11.5%) and 1.4% (95% CI 0.03-7.4%). CONCLUSIONS: The P/F phase of the Kids-DOTT trial has demonstrated the validity of vascular imaging findings of occlusion as a randomization criterion, and defined randomization, retention and endpoint rates to inform the fully powered RCT.
Subject(s)
Anticoagulants/therapeutic use , Venous Thrombosis/drug therapy , Adolescent , Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Child , Child, Preschool , Colorado/epidemiology , Diagnostic Imaging , Endpoint Determination/methods , Feasibility Studies , Female , Florida/epidemiology , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Humans , Infant , Male , Observer Variation , Pilot Projects , Quality Assurance, Health Care , Recurrence , Reproducibility of Results , Research Design , Single-Blind Method , Time Factors , Venous Thrombosis/diagnosis , Young AdultABSTRACT
During primary percutaneous coronary intervention (PCI), manual thrombectomymay reduce distal embolization and thus improve microvascular perfusion. Smalltrials have suggested that thrombectomy improves surrogate and clinical outcomes,but a larger trial has reported conflicting results.MethodsWe randomly assigned 10,732 patients with ST-segment elevation myocardial infarction(STEMI) undergoing primary PCI to a strategy of routine upfront manualthrombectomy versus PCI alone. The primary outcome was a composite of deathfrom cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, orNew York Heart Association (NYHA) class IV heart failure within 180 days. The keysafety outcome was stroke within 30 days.ResultsThe primary outcome occurred in 347 of 5033 patients (6.9%) in the thrombectomygroup versus 351 of 5030 patients (7.0%) in the PCI-alone group (hazard ratio in thethrombectomy group, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P = 0.86). Therates of cardiovascular death (3.1% with thrombectomy vs. 3.5% with PCI alone;hazard ratio, 0.90; 95% CI, 0.73 to 1.12; P = 0.34) and the primary outcome plusstent thrombosis or target-vessel revascularization (9.9% vs. 9.8%; hazard ratio,1.00; 95% CI, 0.89 to 1.14; P = 0.95) were also similar. Stroke within 30 days occurredin 33 patients (0.7%) in the thrombectomy group versus 16 patients (0.3%)in the PCI-alone group (hazard ratio, 2.06; 95% CI, 1.13 to 3.75; P = 0.02).ConclusionsIn patients with STEMI who were undergoing primary PCI, routine manual thrombectomy,as compared with PCI alone, did not reduce the risk of cardiovasculardeath, recurrent myocardial infarction, cardiogenic shock, or NYHA class IV heartfailure within 180 days but was associated with an increased rate of stroke within30 days. (Funded by Medtronic and the Canadian Institutes of Health Research;TOTAL ClinicalTrials.gov number, NCT01149044.
Subject(s)
Infarction , Percutaneous Coronary Intervention , ThrombectomySubject(s)
Acute Coronary Syndrome/drug therapy , Adenosine/analogs & derivatives , Piperazines/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Thiophenes/therapeutic use , Ticlopidine/analogs & derivatives , Acute Coronary Syndrome/economics , Adenosine/therapeutic use , Clinical Trials as Topic , Clopidogrel , Costs and Cost Analysis , Drug Utilization , Evidence-Based Medicine , Humans , International Cooperation , Marketing , Patient Satisfaction , Practice Guidelines as Topic , Prasugrel Hydrochloride , Ticagrelor , Ticlopidine/therapeutic useABSTRACT
AIMS: There are major differences in the prevalence and management of patients with atherothrombotic disease including coronary artery disease (CAD), cerebrovascular disease (CVD) and peripheral artery disease (PAD) across different geographical regions. There is, however, little data allowing comparisons of management and outcomes across broad geographic regions. We aimed to describe geographical differences in baseline characteristics, management and outcomes in stable outpatients with established atherothrombotic disease. METHODS AND RESULTS: From the REACH Registry of atherothrombosis, patients with documented CAD, PAD or CVD and with 4-year follow-up were included. Baseline characteristics, treatments and 4-year outcomes were recorded. Event rates were compared between geographical regions and were adjusted for risk scores predicting ischemic and bleeding events. The analyses of baseline characteristics and medications according to geographical region showed marked differences. For the composite primary outcome (cardiovascular death, non-fatal myocardial infarction (MI) and non-fatal stroke), rates ranged from 12.1% in Japan to 18.2% in Eastern Europe. After adjustment, substantial variations remained: taking North America as a reference, patients from Western Europe and Japan had a lower risk of primary outcome event (hazard ratio (HR) 0.93; p = 0.045, and HR = 0.67; p < 0.001 respectively) whereas patients from Eastern Europe had a higher risk (HR = 1.24; p < 0.001). There were no obvious differences between patients from North America and those from Latin America, the Middle East and Asia. CONCLUSION: There are important variations in the outcomes of patients with atherothrombotic across geographic regions. These observations have important implications for public health and clinical research.
Subject(s)
Atherosclerosis/therapy , Cerebrovascular Disorders/therapy , Coronary Artery Disease/therapy , Health Status Disparities , Healthcare Disparities/trends , Outpatients , Peripheral Arterial Disease/therapy , Practice Patterns, Physicians'/trends , Thrombosis/therapy , Aged , Atherosclerosis/diagnosis , Atherosclerosis/mortality , Cerebrovascular Disorders/diagnosis , Cerebrovascular Disorders/mortality , Coronary Artery Disease/diagnosis , Coronary Artery Disease/mortality , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Peripheral Arterial Disease/diagnosis , Peripheral Arterial Disease/mortality , Prevalence , Registries , Thrombosis/diagnosis , Thrombosis/mortality , Time Factors , Treatment OutcomeABSTRACT
AIMS: Rapid heart rate lowering may be attractive in acute ST-segment elevation myocardial infarction (STEMI). Accordingly we studied the effect of intravenous ivabradine on heart rate in this setting. METHODS AND RESULTS: This was a multicenter randomized double-blind placebo-controlled trial: patients aged 40-80 years were randomized after successful primary percutaneous coronary intervention (PCI) performed within 6 h of STEMI symptom onset. Patients were in sinus rhythm and with heart rate >80 bpm and systolic blood pressure >90 mm Hg. They were randomly assigned (2:1 ratio) to intravenous ivabradine (n=82) (5 mg bolus over 30 s, followed by 5 mg infusion over 8 h) or matching placebo (n=42). The primary outcome measure was heart rate and blood pressure. In both groups, heart rate was reduced over 8 h, with a faster and more marked decrease on ivabradine than placebo (22.2 ± 1.3 vs 8.9 ± 1.8 bpm, p<0.0001). After treatment discontinuation, heart rate was similar in both groups. Throughout the study, there was no difference in blood pressure between groups. There was no difference in cardiac biomarkers (creatine kinase (CK-MB), troponin T and troponin I). On echocardiography performed at baseline and post treatment (median 1.16 days), final left ventricular volumes were lower in the ivabradine group both for left ventricular end-diastolic volume (LVEDV) (87.1 ± 28.2 vs 117.8 ± 21.4 ml, p=0.01) and left ventricular end-systolic volume (LVESV) (42.5 ± 19.0 versus 59.1 ± 11.3 ml, p=0.03) without differences in volume change or left ventricular ejection fraction. CONCLUSION: This pilot study shows that intravenous ivabradine may be used safely to slow the heart rate in STEMI. Further studies are needed to characterize its effect on infarct size, left ventricular function and clinical outcomes in this population.
Subject(s)
Anti-Arrhythmia Agents/administration & dosage , Benzazepines/administration & dosage , Myocardial Infarction/therapy , Percutaneous Coronary Intervention/methods , Tachycardia/drug therapy , Adult , Aged , Aged, 80 and over , Anti-Arrhythmia Agents/adverse effects , Benzazepines/adverse effects , Double-Blind Method , Female , Heart Rate/drug effects , Humans , Infusions, Intravenous , Ivabradine , Male , Middle Aged , Myocardial Infarction/physiopathology , Pilot Projects , Treatment OutcomeABSTRACT
BACKGROUND AND AIMS: SAVOR-TIMI 53 was designed to study the effects of the DPP-4 inhibitor saxagliptin on cardiovascular outcomes in high risk type 2 diabetes patients with diverse levels of diabetes control and background anti-diabetic drugs. The goal of this article is to describe the baseline characteristics of this hypothesis driven study. MATERIALS AND METHODS: A total of 16 496 diabetic patients from North America (31.9%), Western Europe (26.0%), Eastern Europe (17.3%), Latin America (16.4%) and Asia (8.3%), with either established cardiovascular disease (78.3%) or with ≥two additional cardiovascular risk factors (21.7%) were randomised to saxagliptin or placebo. Biomarkers of inflammation and insulin resistance were taken at baseline and 2 years later in order to correlate saxagliptin effect on cardiovascular outcome to its effect on inflammation and insulin resistance. RESULTS: Mean [+/-standard deviation (SD)] age was 65.0 (+/-8.6) years, 66.9% were male, body mass index was 31.2 kg/m² (+/-5.6), mean diabetes duration was 11.9 years (+/-8.9) and the mean HbA1c 8.0% (+/-1.4%). HbA1c < 7% was most prevalent among North Americans (30.8%) and least among Asians (15.1%), whereas HbA1c > 9% was 30.7% in Latin America 27.0% in Asia and 15.1% in North America. Diabetic retinopathy was reported in 12.3% of patients, nephropathy in 17.7% and amputation in 2.5%. Diabetic treatments categories were as follows: no medication (5.4%), 1 oral anti-diabetic drug (OAD) (25.0%), ≥2 OAD (27.7%) and/or insulin (40.9%). The prevalence of micro-albuminuria was twice as high among insulin users compared with users of ≥2 OAD. Baseline statin use (78.3% overall) varied by region. CONCLUSION: The SAVOR-TIMI 53 patient population, with differing background diabetes control and anti-diabetic treatment, provides global representation of diabetic patients with established cardiovascular disease or at high risk for cardiovascular disease and is well-positioned to determine the effect of saxagliptin on cardiovascular events.
Subject(s)
Adamantane/analogs & derivatives , Cardiovascular Diseases/prevention & control , Diabetes Mellitus, Type 2/drug therapy , Dipeptides/therapeutic use , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Adamantane/adverse effects , Adamantane/therapeutic use , Aged , Biomarkers/blood , Body Mass Index , Cardiovascular Diseases/chemically induced , Cardiovascular Diseases/complications , Cardiovascular Diseases/epidemiology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/immunology , Diabetic Angiopathies/epidemiology , Diabetic Angiopathies/physiopathology , Diabetic Angiopathies/prevention & control , Diabetic Nephropathies/epidemiology , Diabetic Nephropathies/prevention & control , Dipeptides/adverse effects , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Drug Therapy, Combination/adverse effects , Female , Humans , Hyperglycemia/epidemiology , Hyperglycemia/prevention & control , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/therapeutic use , Insulin Resistance , Male , Middle Aged , Overweight/complications , Prevalence , Risk Factors , Severity of Illness IndexABSTRACT
OBJECTIVES: Patients on antiplatelet therapy have a gastrointestinal bleeding risk. It is increased by risk factors. The frequency of those risk factors, the prevalence of upper digestive symptoms and their management in patients on antiplatelet agents is unknown. PATIENTS AND METHODS: We performed an observational multi-centred prospective survey among 560 French cardiologists with private practice. Each cardiologist completed a questionnaire for the first four patients treated with antiplatelet agents in primary or secondary prevention. RESULTS: Among the 2182 patients included, (age = 67 ± 11 years; 74% male), 83% had at least one gastrointestinal bleeding risk factor and 38.9% had a history of upper digestive tract symptom. A history of gastrointestinal bleeding was reported in 3.4% and a history of documented gastro-duodenal ulcer in 5.5%. A proton pump inhibitor was already prescribed in 39% of the patients. At the time of the consultation, upper digestive symptoms were described in 21% of the patients. In those patients with symptoms, 85% had no modification in antiplatelet therapy and 62.7% were prescribed gastro-protective drugs (proton pump inhibitors: 51.8%, H(2)-blockers 3.6% other anti-acid medication: 7.3%). CONCLUSION: Among patients on antiplatelet agents, the prevalence of upper digestive symptoms and risk factors for gastrointestinal bleeding is high. Preventative management needs to be clarified in this population.
Subject(s)
Gastrointestinal Agents/therapeutic use , Outpatients/statistics & numerical data , Peptic Ulcer Hemorrhage/chemically induced , Peptic Ulcer Hemorrhage/prevention & control , Physicians/statistics & numerical data , Platelet Aggregation Inhibitors/adverse effects , Stomach Ulcer/chemically induced , Stomach Ulcer/prevention & control , Aged , Anti-Ulcer Agents/therapeutic use , Cardiology , Cardiovascular Diseases/prevention & control , Drug Therapy, Combination , Female , France/epidemiology , Gastrointestinal Hemorrhage/chemically induced , Gastrointestinal Hemorrhage/prevention & control , Health Care Surveys , Histamine H2 Antagonists/therapeutic use , Humans , Male , Middle Aged , Peptic Ulcer Hemorrhage/epidemiology , Platelet Aggregation Inhibitors/administration & dosage , Prevalence , Private Practice , Prospective Studies , Proton Pump Inhibitors/therapeutic use , Risk Factors , Stomach Ulcer/epidemiology , Surveys and Questionnaires , Treatment Outcome , Upper Gastrointestinal Tract/drug effectsABSTRACT
OBJECTIVES: To obtain Western European perspectives on the economic burden of atherothrombosis in patients with multiple risk factors only (MRF), cerebrovascular disease (CVD), coronary artery disease (CAD), and in the under-evaluated group of patients with peripheral arterial disease (PAD), we examined vascular-related hospitalisation rates and associated costs in France and Germany. DESIGN: The prospective REACH Registry enrolled 4693 patients in France, and 5594 patients in Germany (from December 2003 until June 2004). METHODS: For each country, 2-year rates and costs associated with cardiovascular events and vascular-related hospitalisations were examined for patients with MRF, CVD, CAD, and PAD. RESULTS: Two-year hospitalisation costs were highest for patients with PAD (3182.1 for France; 2724.4 for Germany) and lowest for the MRF group (749.1 for France; 503.3 for Germany). Peripheral revascularizations and amputations were the greatest contributors to costs for all risk groups. Across all PAD subgroups, peripheral procedures constituted approximately half of the 2-year costs. CONCLUSION: Hospitalisation rates and costs associated with atherothrombotic disease in France and Germany are high, especially so for patients with PAD.
Subject(s)
Cerebrovascular Disorders/economics , Coronary Artery Disease/economics , Health Care Costs , Hospitalization/statistics & numerical data , Peripheral Arterial Disease/economics , Thrombosis/economics , Aged , Aged, 80 and over , Cerebrovascular Disorders/diagnosis , Cerebrovascular Disorders/surgery , Coronary Artery Disease/diagnosis , Coronary Artery Disease/surgery , Cost of Illness , Female , Follow-Up Studies , France , Germany , Humans , Male , Middle Aged , Peripheral Arterial Disease/diagnosis , Peripheral Arterial Disease/surgery , Prospective Studies , Registries , Risk Factors , Thrombosis/etiologyABSTRACT
Paraoxonase-1 (PON1) Q192R polymorphism was recently suggested to determine per se clopidogrel response on major cardiovascular events (MACEs). We assessed the impact of PON1, CYP2C19, and ABCB1 polymorphisms on MACE in clopidogrel-treated acute myocardial infarction (AMI) patients (N = 2,210), including those undergoing percutaneous coronary intervention (PCI) (n = 1,538). PON1 polymorphism was not associated with increased risk of in-hospital death and MACEs at 1 year (adjusted hazard ratio (HR) 1.03, 95% confidence interval (CI) 0.66-1.61 and adjusted HR 0.77, 95% CI 0.42-1.41 for QQ versus RR in all and PCI patients, respectively). The presence of two CYP2C19 loss-of-function (LOF) alleles was associated with the risk of in-hospital death and MACEs at 1 year in the overall population (adjusted odds ratio (OR) 3.67, 95% CI 1.05-12.80 and adjusted HR 1.96, 95% CI 1.08-3.54) and in PCI patients (adjusted OR 6.87, 95% CI 2.52-18.72 and adjusted HR 3.06, 95% CI 1.47-6.41). Unlike CYP2C19 polymorphism, PON1 (Q192R) polymorphism is not a major pharmacogenetic contributor of clinical response to clopidogrel in AMI patients.
Subject(s)
Aryldialkylphosphatase/genetics , Myocardial Infarction/drug therapy , Myocardial Infarction/genetics , Polymorphism, Genetic/genetics , Ticlopidine/analogs & derivatives , Aged , Aged, 80 and over , Clopidogrel , Female , Follow-Up Studies , Genotype , Hospital Mortality/trends , Humans , Male , Middle Aged , Myocardial Infarction/mortality , Prospective Studies , Registries , Ticlopidine/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND: Patients receiving anti-platelet agents for secondary cardiovascular prevention frequently require non-cardiac surgery. A substantial proportion of these patients have their anti-platelet drug discontinued before operation; however, there is uncertainty about the impact of this practice. The aim of this study was to compare the effect of maintenance or interruption of aspirin before surgery, in terms of major thrombotic and bleeding events. METHODS: Patients treated with anti-platelet agents for secondary prevention and undergoing intermediate- or high-risk non-cardiac surgery were included in this multicentre, randomized, placebo-controlled, trial. We substituted non-aspirin anti-platelets with aspirin (75 mg daily) or placebo starting 10 days before surgery. The primary outcome was a composite score evaluating both major thrombotic and bleeding adverse events occurring within the first 30 postoperative days weighted by their severity (weights were established a priori using a Delphi consensus process). Analyses followed the intention-to-treat principle. RESULTS: We randomized 291 patients (n=145, aspirin group, and n=146, placebo group). The most frequent surgical procedures were orthopaedic surgery (52.2%), abdominal surgery (20.6%), and urologic surgery (15.5%). No significant difference was observed neither in the primary outcome score [mean values (SD)=0.67 (2.05) in the aspirin group vs 0.65 (2.04) in the placebo group, P=0.94] nor at day 30 in the number of major complications between groups. CONCLUSIONS: In these at-risk patients undergoing elective non-cardiac surgery, we did not find any difference in terms of occurrence of major thrombotic or bleeding events between preoperative maintenance or interruption of aspirin.
Subject(s)
Aspirin/therapeutic use , Elective Surgical Procedures , Platelet Aggregation Inhibitors/therapeutic use , Postoperative Hemorrhage/chemically induced , Preoperative Care , Thrombosis/prevention & control , Aged , Aspirin/administration & dosage , Female , Humans , Male , Middle AgedABSTRACT
AIMS: Occlusive coronary artery disease (CAD) is associated with left ventricular (LV) remodeling, LV systolic dysfunction, and heart failure. The BEAUTIFUL Echo substudy aimed to evaluate the effects of heart rate reduction with ivabradine on LV size (primary end-point: change in LV end-systolic volume index [LVESVI]) and function and the cardiac biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP). METHODS AND RESULTS: The substudy was carried out in 86 centers participating in the BEAUTIFUL study. 2D echocardiography was performed at baseline, and after 3 and 12 months in patients with stable CAD and LV systolic dysfunction receiving ivabradine or placebo at the same time-points. All data were read and analyzed centrally. Of 525 patients completing the study, 426 had adequate echocardiographic readings (n = 220 ivabradine; n = 206 placebo). Treatment with ivabradine was associated with a decrease in the primary end-point LVESVI (change from baseline to last value, -1.48 ± 13.00 mL/m(2)) versus an increase with placebo (1.85 ± 10.54 mL/m(2)) (P=0.018). There was an increase in LV ejection fraction with ivabradine (2.00 ± 7.02%) versus no change with placebo (0.01 ± 6.20%) (P=0.009). Reduction in LVESVI was related to the degree of heart rate reduction with ivabradine. There were no differences in any other echocardiographic parameters or NT-proBNP. Change in LVESVI was related to the log change in NT-proBNP in the ivabradine group only (r = 0.18, P = 0.006). CONCLUSIONS: Our observations suggest that ivabradine may reverse detrimental LV remodeling in patients with CAD and LV systolic dysfunction.
Subject(s)
Benzazepines/pharmacology , Coronary Occlusion/diagnostic imaging , Coronary Occlusion/drug therapy , Heart Rate/drug effects , Ventricular Remodeling/drug effects , Aged , Double-Blind Method , Female , Humans , Ivabradine , Male , UltrasonographyABSTRACT
OBJECTIVE: To clarify the differences in the baseline characteristics, prevalence and incidence of atherothrombosis in patients recruited from Asia versus non-Asian regions. DESIGN: International Prospective Cohort Study. SETTING: Region focused substudy. PATIENTS: The Reduction of Atherothrombosis for Continued Health (REACH) Registry recruited 68â 236 stable outpatients with established atherothrombosis or ≥3 atherothrombotic risk factors from 44 countries. INTERVENTIONS: No intervention. MAIN OUTCOME MEASURES: Risk factors, use of medications, vascular disease bed location, and 1-year cardiovascular (CV) outcomes (CV death, myocardial infarction, stroke). RESULTS: The percentages of patients recruited with CVD (Cerebrovascular Disease) were higher in Asia (41.0%) than in non-Asian regions (25.1%) (p<0.0001). The prevalence of diabetes mellitus was higher in Asia (46.6%) than in non-Asian regions (43.3%) (p<0.0001) despite the former having a lower body mass index (BMI) (24.4±3.9 vs 28.8±5.6) (p<0.0001). The combined endpoint of CV death/myocardial infarction/stroke of patients recruited from non-Asian regions of 4.38% (95% CI 4.20 to 4.56) is equivalent to those from the Asian region excluding Japan of 4.65% (95% CI 4.04 to 5.25), but that is significantly lower in patients recruited from Japan of 3.40% (95% CI 2.76 to 4.04, p<0.05). CONCLUSIONS: There is a higher prevalence of CVD and higher prevalence of diabetus mellitus with lower body mass index in patients recruited from the Asian region as compared those recruited from non-Asian regions. The CV event rate in patients recruited from non-Asian regions is equivalent to that of patients recruited from the Asian region excluding Japan, but significantly lower in patients recruited from Japan.
ABSTRACT
OBJECTIVES: Poor blood pressure (BP) control is common amongst patients with symptomatic atherothrombotic disease. It is unclear whether BP control and management differ across atherothrombotic disease subtypes. METHODS: We analysed the baseline data of 44,984 patients with documented coronary artery disease (CAD) only (n = 30,414), cerebrovascular disease (CVD) only (n = 11,359) and peripheral arterial disease (PAD) only (n = 3211) from the international REduction of Atherothrombosis for Continued Health Registry and investigated the impact of atherothrombotic disease subtype on BP control and use of antihypertensive drugs. RESULTS: The proportion of patients with BP controlled (<140/90 mmHg) was higher in CAD (58.1%) than in CVD (44.8%) or PAD (38.9%) patients (P < 0.001). Amongst patients with treated hypertension, CAD patients were more likely to have BP controlled than were CVD patients [odds ratio (OR) = 1.67; 95% confidence interval (CI) = 1.59-1.75] or PAD (OR = 2.30; 95% CI = 2.10-2.52). These differences were smaller in women than in men and decreased with age. Amongst treated patients, CAD patients were more likely to receive > or =3-drug combination therapies than were CVD (OR = 1.73; 95% CI = 1.64-1.83) or PAD (OR = 1.64; 95% CI = 1.49-1.80) patients. Adjustment for age, gender, waist obesity, diabetes, education level and world region did not alter the results. CONCLUSIONS: Coronary artery disease patients are more likely than CVD or PAD patients to have BP controlled and to receive antihypertensive drugs, particularly combination therapies. Promotion of more effective BP control through combination antihypertensive therapies could improve secondary prevention and therefore prevent complications in CVD and PAD patients.
Subject(s)
Blood Pressure , Cerebrovascular Disorders/physiopathology , Coronary Artery Disease/physiopathology , Hypertension/drug therapy , Peripheral Vascular Diseases/physiopathology , Age Factors , Aged , Antihypertensive Agents/therapeutic use , Cerebrovascular Disorders/drug therapy , Coronary Artery Disease/drug therapy , Female , Humans , Male , Middle Aged , Peripheral Vascular Diseases/drug therapy , Sex FactorsABSTRACT
PURPOSE: To use diffusion weighted MR imaging (DWI), a technique routinely used in patients with stroke, for diagnosis of myocardial infarction (MI). MATERIALS AND METHODS: A breath hold ECG gated DWI sequence (b = 300 sec/mm2) was developped and applied to 7 patients with recent MI (3-15 days), 3 patients with chronic MI (> 6 months) and 4 patients with valvular heart disease without MI (control cases). DWI data were correlated to T2W, first pass perfusion and delayed enhancement data. RESULTS: In all patients with recent MI, DWI showed an area of increased signal with reduction of ADC relative to normal myocardium. Hyperintense lesion on DWI corresponded to areas of delayed enhancement. The diffusion images were normal in patients with chronic MI or no MI. CONCLUSION: Even though no animal model or other reference method is available, these preliminary results indicate that DWI could assist clinicians in detecting recent MI.