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Biomedical subjects

G Agnelli

Publications and source records attributed to G Agnelli.

At least 37 records · Page 2Linked to original sources
PubMed2002

Sulodexide in the treatment of intermittent claudication. Results of a randomized, double-blind, multicentre, placebo-controlled study.

AIMS: Patients with peripheral arterial obstructive disease require treatment to prevent major cardiovascular events and to relieve intermittent claudication. The walking performance of peripheral arterial obstructive disease patients was used to evaluate the usefulness of sulodexide, a glycosaminoglycan containing fast moving heparin and dermatan sulphate. METHODS AND RESULTS: A randomized, multicentre, double-blind, placebo-controlled study was performed in 286 patients with Leriche-Fontaine stage II peripheral arterial obstructive disease. Patients received placebo (n=143) or sulodexide (n=143) for 27 weeks. The primary end-point was the doubling of the pain-free walking distance at the end of treatment, and this was achieved by 23.8% of patients treated with sulodexide and 9.1% of those on placebo (P=0.001). The pain-free walking distance increased on average (+/-SE) by 83.2+/-8.6 m (+64.7% from baseline) with sulodexide and 36.7+/-6.2 m (+29.9% from baseline) with placebo (P=0.001). The maximum walking distance increased by 142.3+/-15.8 m (+76.0% from baseline) and 54.5+/-8.4 m (+27.9% from baseline) (P<0.001), respectively. Results for patients with type II diabetes were similar to those for non-diabetic patients. Plasma fibrinogen decreased with sulodexide, but increased with placebo. CONCLUSION: Sulodexide improved the walking ability of peripheral arterial obstructive disease patients to a significantly greater extent than placebo, with a concurrent significant decrease in fibrinogen. The treatment was well tolerated.

Aged↗
PubMed2001

Risk factors for adverse short-term outcome in patients with pulmonary embolism.

Pulmonary embolism (PE) is a common and potentially fatal disease. Death usually occurs before hospital admission or in the initial in-hospital phase. A number of clinical and instrumental findings have been associated with a high risk of adverse short-term clinical outcomes in patients with PE. Advanced age, concomitant cardiopulmonary disease, and haemodynamic instability, as well as large perfusion defects at lung scanning and acute right heart dysfunction as assessed by echocardiography, are associated with adverse in-hospital outcome. Elevated serum levels of troponin I have been recently demonstrated to be associated with severe right ventricular dysfunction and adverse in-hospital outcome in patients with PE. Early recurrence of PE is associated with a high mortality rate. Right heart dysfunction, as assessed by echocardiography and an acute fall in platelet count, have been suggested as risk factors for recurrence of PE. A reduction in mortality in the subgroup of patients with a poor prognosis might be achieved by using more aggressive treatments such as thrombolysis and surgical or interventional procedures. However, such treatments are invariably associated with bleeding and other procedural complications.

Humans↗
PubMed2001

Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis. Warfarin Optimal Duration Italian Trial Investigators.

BACKGROUND: In patients with idiopathic deep venous thrombosis, continuing anticoagulant therapy beyond three months is associated with a reduced incidence of recurrent thrombosis during the period of therapy. Whether this benefit persists after anticoagulant therapy is discontinued is controversial. METHODS: Patients with a first episode of idiopathic proximal deep venous thrombosis who had completed three months of oral anticoagulant therapy (with warfarin, in 97 percent of the cases and acenocoumarol in 3 percent) were randomly assigned to the discontinuation of oral anticoagulants or to their continuation for nine additional months. The primary study outcome was recurrence of symptomatic, objectively confirmed venous thromboembolism during at least two years of follow-up. RESULTS: The primary intention-to-treat analysis showed that of 134 patients assigned to continued oral anticoagulant therapy, 21 had a recurrence of venous thromboembolism (15.7 percent; average follow-up, 37.8 months), as compared with 21 of 133 patients assigned to the discontinuation of oral anticoagulant therapy (15.8 percent; average follow-up, 37.2 months), resulting in a relative risk of 0.99 (95 percent confidence interval, 0.57 to 1.73). During the initial nine months after randomization (after all patients received three months of therapy), 1 patient had a recurrence while receiving oral anticoagulant therapy (0.7 percent), as compared with 11 of the patients assigned to the discontinuation of oral anticoagulant therapy (8.3 percent; P=0.003). The incidence of recurrence after the discontinuation of treatment was 5.1 percent per patient-year in patients in whom oral anticoagulant therapy was discontinued after 3 months (95 percent confidence interval, 3.2 to 7.5 percent; average interval since discontinuation, 37.2 months) and 5.0 percent per patient-year in patients who received an additional 9 months of oral anticoagulant therapy (95 percent confidence interval, 3.1 to 7.8 percent; average interval since discontinuation, 29.4 months). None of the recurrences were fatal. Four patients had non-fatal major bleeding during the extended period of anticoagulant therapy (3.0 percent). CONCLUSIONS: In patients with idiopathic deep venous thrombosis, the clinical benefit associated with extending the duration of anticoagulant therapy to one year is not maintained after the therapy is discontinued.

Acenocoumarol↗
PubMed2001

Dose-response study of recombinant factor VIIa/tissue factor inhibitor recombinant nematode anticoagulant protein c2 in prevention of postoperative venous thromboembolism in patients undergoing total knee replacement.

BACKGROUND: With the best prophylactics now available, venous thromboembolism after total knee replacement remains substantial (25% to 27%). Recombinant nematode anticoagulant protein c2 (rNAPc2) is a potent inhibitor of factor VIIa/tissue factor complex that has the potential to reduce this risk. The present study was performed to determine an efficacious and safe dose of rNAPc2 for prevention of venous thromboembolism after elective, unilateral total knee replacement. METHODS AND RESULTS: This open-label, sequential dose-ranging study was conducted in 11 centers in Canada, Europe, and the United States. Five regimens were tested. Injections were administered subcutaneously on the day of surgery (day 1) and days 3, 5, and optionally, day 7. Primary efficacy outcome was a composite of overall deep vein thrombosis based on mandatory unilateral venography (day 7+/-2) and confirmed symptomatic venous thromboembolism recorded </=48 hours after the last dose of rNAPc2. Primary safety outcome was major bleeding </=72 hours after the last dose. An independent, blinded Central Adjudication Committee assessed all outcome events. Of 293 patients studied, 251 (86%) could be evaluated for primary efficacy analysis. A dosage of 3.0 microgram/kg administered within 1 hour after surgery provided the best observed results, with an overall deep vein thrombosis rate of 12.2%, a proximal deep vein thrombosis rate of 1.3%, and a major bleeding rate of 2.3%. CONCLUSIONS: A randomized, double-blind trial that compared rNAPc2 with current best prophylactics is warranted based on encouraging, first-reported clinical results for a factor VIIa/tissue factor inhibitor evaluated for thrombosis prophylaxis.

Aged↗
PubMed2001

Clinical and economic aspects of managing venous thromboembolism in the outpatient setting.

Low-molecular-weight heparins (LMWHs) are at least as effective and safe as unfractionated heparin (UFH) in the prevention and initial treatment of venous thromboembolism (VTE), and their fixed-dose, once- or twice-daily dosing regimen without laboratory monitoring makes them suitable for outpatient use. Postoperative thromboprophylaxis usually continues until hospital discharge, but evidence demonstrates that the VTE risk persists for several weeks. Economic pressures, changes in clinical practice, and patient preferences make hospital stays shorter. As a result, outpatient thromboprophylaxis with LMWH has been investigated. LMWH self-administered at home once daily for up to 4 weeks after hospital discharge is safe and well tolerated and significantly reduces the incidence of postdischarge VTE after hip replacement. Targeted appropriately, extended thromboprophylaxis may be cost effective, and the development of an autoinjection device may increase the proportion of patients eligible for home management. LMWHs may also be of value as long-term secondary thromboprophylaxis in patients with contraindications to oral anticoagulants. Standard initial treatment for VTE comprises intravenous UFH administered to the patient in the hospital. However, three large-scale studies have demonstrated the efficacy and safety of outpatient treatment of acute VTE using LMWHs. The economic benefits of shortening or eliminating inpatient therapy are substantial, but successful home treatment requires careful patient selection, intensive education and a comprehensive system of professional support to optimize compliance and safety.

Ambulatory Care↗
PubMed2001

End points in studies on the prevention of deep vein thrombosis.

Clinically overt events are of obvious relevance for the outcome of patients. There is unanimous consensus of clinicians that these events should be prevented in clinical practice. In clinical trials on the prevention of deep vein thrombosis, symptomatic objectively confirmed venous thromboembolism is the most important outcome to be measured. However, because of the difficulties related to the measurement of clinically overt events, venography is the most commonly used method for end-point measurement in clinical trials on the prevention of venous thromboembolism. The limitations of venography leave a great need for the development of accurate noninvasive methods to be used as alternatives to venography. The end point must be tailored to the phase of the clinical trial. In phase I/II clinical trials, that are designed to evaluate the effectiveness of thromboprophylactic agents, it still is necessary to use the most accurate method for the diagnosis of deep vein thrombosis and to perform bilateral venography. When a new pharmacologic agent is compared with the "gold standard" agent, the use of symptomatic end points should be preferable.

Clinical Trials as Topic↗
PubMed2001

Rationale for the use of platelet aggregation inhibitors in PAD patients.

Peripheral arterial disease (PAD) is a major risk marker for systemic ischaemic events. The understanding of PAD has moved from PAD as an organ-specific disease to PAD as the lower-limb localization of a multifocal disease, i.e. atherothrombosis. Blood platelet activation and aggregation is a common denominator in atherothrombotic events, and use of antiplatelet agents in patients with PAD can inhibit thrombus formation and reduce the occurrence of myocardial infarction (MI), ischaemic stroke (IS) and vascular death. Many studies have investigated various antiplatelet regimens for preventing acute cardiovascular events in patients with a prior ischaemic event, although many of these studies had a number of limitations. The Antiplatelet Trialists' Collaboration performed a meta-analysis of 23 stroke trials and found an average odds risk reduction of 25% for a combined endpoint of stroke, MI or vascular death. The concept of atherothrombosis as a multifocal disease was challenged by the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) trial. This study showed an 8.7% decrease in the relative risk reduction for further atherothrombotic events with clopidogrel over aspirin (p = 0.043) for the overall population, in terms of the combined endpoint of IS, Ml or vascular death.

Aspirin↗
PubMed2000

Short-term clinical outcome of patients with acute pulmonary embolism, normal blood pressure, and echocardiographic right ventricular dysfunction.

BACKGROUND: The role of echocardiographic right ventricular (RV) dysfunction in predicting clinical outcome in clinically stable patients with pulmonary embolism (PE) is undefined. In this study, we assessed the prevalence and clinical outcome of normotensive patients with RV dysfunction among a broad spectrum of PE patients. METHODS AND RESULTS: This prospective clinical outcome study included cohort of 209 consecutive patients (age, 65+/-15 years) with documented PE. Acute RV dysfunction was diagnosed in the presence of >/=1 of the following: RV dilatation (without hypertrophy), paradox septal systolic motion, and Doppler evidence of pulmonary hypertension. Four groups were identified: 28 patients presenting with shock or cardiac arrest (13%), 19 hypotensive patients without shock (9%), 65 normotensive patients with echocardiographic RV dysfunction (31%), and 97 normotensive patients without RV dysfunction (47%). Among normotensive patients with RV dysfunction, 6 (10%) developed PE-related shock after admission: 3 of these patients died, and 3 were successfully treated with thrombolytic agents. In comparison, none of the 97 normotensive patients without RV dysfunction developed shock or died as a result of PE. CONCLUSIONS: A significant proportion (31%) of normotensive patients with acute PE presents with RV dysfunction; these patients with latent hemodynamic impairment have a 10% rate of PE-related shock and 5% in-hospital mortality and may require aggressive therapeutic strategies. Conversely, normotensive patients without echocardiographic RV dysfunction have a benign short-term prognosis. Thus, early detection of echocardiographic RV dysfunction is of major importance in the risk stratification of normotensive patients with acute PE.

Acute Disease↗
PubMed2000

Prevention of venous thromboembolism.

Venous thromboembolism is the most common cause of preventable death among hospitalised patients. Systematic prophylaxis with antithrombotic agents in patients at risk for venous thromboembolism is the most effective approach to reduce morbidity and mortality. Despite this evidence, antithrombotic prophylaxis is still underused, due to the underestimation of incidence of venous thromboembolism and to the unjustified fear of bleeding complications. Both the characteristics of the individual patient and the clinical setting contribute to the definition of the risk for venous thromboembolism. Patient-related risk factors include clinical and molecular abnormalities. The grade of risk for venous thromboembolism is defined better by the clinical setting than by the patient characteristics. Prophylactic studies have been extensively carried out in surgical patients and, only more recently, in medical patients. Prophylactic methods include pharmacological agents, such as heparin, low molecular weight heparins, warfarin, and hirudin, as well as mechanical methods such as compression stockings and intermittent pneumatic compression.

Anticoagulants↗
PubMed2000

Management of thromboembolism in the outpatient setting.

Low-molecular-weight heparins (LMWHs) are suitable for self-administration at home, because they have a predictable anticoagulant effect following subcutaneous injection and do not require laboratory monitoring. Clinical trials evaluating the safety and efficacy of LMWHs in the outpatient setting for the prevention of deep vein thrombosis (DVT) after orthopedic surgery and for the treatment of established DVT are reviewed. Extended LMWH prophylaxis reduces the incidence of venographically detected DVT by approximately 50%. Medical practice relies heavily on clinical diagnosis of DVT, for which both sensitivity and specificity are poor. It is uncertain how the results of research trials on DVT prevention based on venography relate to ordinary practice. In the treatment of established DVT, there was no significant difference between outpatient management with LMWH and inpatient treatment with unfractionated heparin (UFH). However, outpatient management offered a considerable reduction in resource usage, with associated cost savings.

Ambulatory Care↗
PubMed2000

Low-molecular-weight heparins in the management of unstable angina.

Low-molecular-weight heparins (LMWHs) are derivatives of unfractionated heparin (UFH) and have a more favourable pharmacokinetic profile and a more predictable anticoagulant effect than UFH. These features allow the subcutaneous injection of weight-adjusted doses of LMWHs without monitoring of blood coagulation, and this results in cost savings. Clinical trials have shown that combined therapy with aspirin and LMWHs is significantly more effective than aspirin alone in reducing the risk of cardiac events in the acute treatment of patients affected by unstable angina. LMWHs have also been shown to be at least as safe and effective as UFH in reducing the incidence of death and myocardial infarction in patients with unstable angina. LMWHs appear to be at least as safe as UFH with regard to major bleeding risk. When given as extended therapy, LMWHs have been shown to be superior to placebo at 30 and 45 days, with an acceptable risk of bleeding. Additionally, LMWHs can be used as a 'bridge' to revascularization in patients for whom early invasive treatment is not readily available.

Angina, Unstable↗
PubMed2000

The rationale for long-term prophylaxis of venous thromboembolism.

Prophylaxis for venous thromboembolism (VTE) after surgery has traditionally been given from the time of surgery until hospital discharge, typically ranging from 5-14 days. Recently, there has been a trend toward shorter periods of hospitalization. Furthermore, a number of prospective studies have demonstrated that a significant proportion of patients develop deep vein thrombosis (DVT) or pulmonary embolism (PE) up to 5 or 6 weeks following general or orthopedic surgery. Therefore, prolonged prophylaxis during the post-discharge period may provide clinical benefits in high-risk patients. However, the optimal duration of prophylaxis for VTE after surgery remains unclear. In elective hip replacement, four studies of prolonged prophylaxis with low-molecular-weight heparin (LMWH) for 3- 4 weeks after hospital discharge demonstrated a significant reduction in the incidence of venography-confirmed DVT. These results support the use of prolonged thromboprophylaxis in the outpatient setting. Effective outpatient prophylaxis must be safe and convenient for patients to maximize compliance and clinical benefits. Low-molecular-weight heparins are safe and effective when given at a fixed daily dose, and pharmacoeconomic studies suggest that prolonged prophylaxis with these agents may be cost-effective. Key challenges for the future include identifying the patients who require prolonged prophylaxis and determining the duration of treatment.

Anticoagulants↗
PubMed1999

Dermatan sulphate in patients with heparin-induced thrombocytopenia.

Patients with thromboembolic diseases who develop heparin-induced thrombocytopenia (HIT) type II require an alternative anticoagulation strategy. Dermatan sulphate (DS) was administered to five patients with thromboembolic diseases who developed HIT type II and showed an in vitro cross-reactivity with low molecular weight heparins. The platelet count and the extension of thrombosis were monitored during DS administration. In four of the five patients the platelet count rapidly increased after heparin was discontinued and DS started. A low platelet count persisted in the single patient with cross-reactivity to DS, up to 4 d after its discontinuation. None of the patients experienced thrombus extension, haemorrhagic side-effects or other adverse events.

Adult↗