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Biomedical subjects

A G Turpie

Publications and source records attributed to A G Turpie.

At least 19 recordsLinked to original sources
PubMed1998

Economic assessment of low-molecular-weight heparin (enoxaparin) versus unfractionated heparin in acute coronary syndrome patients: results from the ESSENCE randomized trial. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q wave Coronary Events [unstable angina or non-Q-wave myocardial infarction].

BACKGROUND: In the ESSENCE trial, subcutaneous low-molecular-weight heparin (enoxaparin) reduced the 30-day incidence of death, myocardial infarction, and recurrent angina relative to intravenous unfractionated heparin in 3171 patients with acute coronary syndrome (unstable angina or non-Q-wave myocardial infarction). No increase in major bleeding was seen. METHODS AND RESULTS: Of the 936 ESSENCE patients randomized in the United States, 655 had hospital billing data collected. For the remainder, hospital costs were imputed with a multivariable linear regression model (R2=.86). Physician fees were estimated from the Medicare Fee Schedule. During the initial hospitalization, major resource use was reduced for enoxaparin patients, with the largest effect seen with coronary angioplasty (15% versus 20% for heparin, P=.04). At 30 days, these effects persisted, with the largest reductions seen in diagnostic catheterization (57% versus 63% for heparin, P=.04) and coronary angioplasty (18% versus 22%, P=.08). All resource use trends seen in the US cohort were also evident in the overall ESSENCE study population. In the United States, the mean cost of a course of enoxaparin therapy was $155, whereas that for heparin was $80. The total medical costs (hospital, physician, drug) for the initial hospitalization were $11 857 for enoxaparin and $12620 for heparin, a cost advantage for the enoxaparin arm of $763 (P=.18). At the end of 30 days, the cumulative cost savings associated with enoxaparin was $1172 (P=.04). In 200 bootstrap samples of the 30-day data, 94% of the samples showed a cost advantage for enoxaparin. CONCLUSIONS: In patients with acute coronary syndrome, low-molecular-weight heparin (enoxaparin) both improves important clinical outcomes and saves money relative to therapy with standard unfractionated heparin.

Acute Disease↗
PubMed1998

Compression ultrasonography for diagnostic management of patients with clinically suspected deep vein thrombosis: prospective cohort study.

OBJECTIVE: To evaluate the safety of withholding anticoagulant treatment from patients with clinically suspected deep vein thrombosis but normal findings on compression ultrasonography. DESIGN: Compression ultrasonography was done with a simplified diagnostic procedure limited to the common femoral vein in the groin and the popliteal vein extending down to the trifurcation of the calf veins. Patients with normal ultrasonography findings at presentation were retested 1 week later. MAIN OUTCOME MEASURE: The incidence of venous thromboembolic complications during follow up for 6 months in patients in whom anticoagulant treatment was withheld on the basis of normal results on two ultrasonography tests 1 week apart. SETTING: University research centres in four hospitals. RESULTS: A total of 1702 patients were included in the study. Abnormal results on compression ultrasonography at presentation or at 1 week were found in 400 and 12 patients, respectively, for a prevalence of deep vein thrombosis of 24%. None of the patients were lost to follow up. Venous thromboembolic complications during the week of serial testing occurred in a single patient and in eight patients during 6 months' follow up, resulting in a cumulative rate of venous thromboembolic complications of 0.7% (95% confidence interval 0.3% to 1.2%). The mean number of extra hospital visits and additional tests required per initially referred patient was 0.8. CONCLUSION: It is safe to withhold anticoagulant treatment from patients with clinically suspected deep vein thrombosis who have a normal result on compression ultrasonography at the time of presentation and at 1 week.

Adolescent↗
PubMed1998

Management strategies for a better outcome in unstable coronary artery disease.

Unstable coronary artery disease is a term encompassing both unstable angina and non-Q-wave (non-ST-segment elevation) myocardial infarction. Patients with these conditions are at risk of early progression to acute myocardial infarction and death. Thus, management of these conditions must aim to reduce long-term mortality and morbidity. Risk stratification is crucial for the identification of patients whose risk of early progression is high; they may require coronary angiography and (if suitable) either percutaneous transluminal coronary angioplasty or coronary artery bypass surgery. No single variable can accurately predict risk, but considerable data are emerging to show that biochemical markers of myocardial injury, such as troponin-T and troponin-I, are valuable in combination with electrocardiographic findings and clinical features. Routine early invasive procedures (coronary angiography with or without revascularization) have not yet been shown to have any significant advantage over conservative regimens for the majority of patients. Antiplatelet, anticoagulant, and anti-ischemic agents remain the mainstay of treatment in the acute phase. New agents, such as glycoprotein IIb/IIIa receptor inhibitors and low-molecular-weight heparins, as well as antithrombins and Factor Xa inhibitors add to the treatments currently available. Thrombolytic agents are contraindicated in the absence of ST-segment elevation. After clinical stabilization, ongoing assessment should include exercise testing for all patients who are able; other imaging techniques should be used for patients unable to exercise. A profile indicating a high risk of future events is an indication for elective angiography and consideration for revascularization.

Algorithms↗
PubMed1998

Pharmacology of the low-molecular-weight heparins.

Unfractionated heparin (UFH) is widely used to both treat and prevent venous thromboembolism. More recently, UFH has been used to prevent death and myocardial infarction in patients with unstable angina or acute myocardial infarction and acute occlusion in those undergoing percutaneous coronary revascularization. However, its poor bioavailability (when administered in low doses subcutaneously), its mechanism of clearance, and its short half-life make its anticoagulant activity difficult to predict and maintain. To overcome these limitations, low-molecular-weight heparins (LMWHs) have been developed that have greater bioavailability and a longer half-life in plasma. Because LMWHs provide more predictable anticoagulant activity compared with subcutaneous UFH, it is not necessary to monitor the activated partial thromboplastin time during treatment. These newer agents are as effective as UFH in the prophylaxis and treatment of thromboembolic and cardiac disorders and, by allowing shorter hospital stays, are more cost effective. Thus LMWHs offer clear pharmacokinetic advantages over UFH. More studies are needed to determine the extent to which clinically available LMWHs can be used in place of UFH.

Anticoagulants↗
PubMed1997

Guidelines for management of left-sided prosthetic valve thrombosis: a role for thrombolytic therapy. Consensus Conference on Prosthetic Valve Thrombosis.

OBJECTIVES: We sought to form a consensus recommendation for management of prosthetic valve thrombosis (PVT) from previous case and uncontrolled reports from a consensus of international specialists. BACKGROUND: PVT and thromboembolism relate to inadequate anticoagulation and valve type and location. PVT is suspected by history (dyspnea) and auscultation (muffled valve sounds or new murmurs) and confirmed by Doppler echocardiography showing a marked valve gradient. METHODS: A consensus conference was held to recommend management of left-sided PVT. RESULTS: Transesophageal Doppler echocardiography is used to visualize abnormal leaflet motion and the size, location and mobility of thrombus. Thrombolysis is used for high risk surgical candidates with left-sided PVT (New York Heart Association functional class III or IV) because cerebral thromboembolism may occur in 12% of patients. Duration of thrombolysis depends on resolution of pressure gradients and valve areas to near normal by Doppler echocardiography performed every few hours. Lysis is stopped after 72 or 24 h if there is no hemodynamic improvement (operation indicated). Heparin infusion with frequent measurement of activated partial thromboplastin time (aPTT) begins when aPTT is more than twice control levels and can be converted to warfarin (international normalized ratio [INR] 2.5 to 3.5) plus aspirin (81 to 100 mg/day). Patients in functional class I or II have lower surgical mortality, and those with large immobile thrombi on the prosthetic valve or left atrium have responded to endogenous lysis with combined subcutaneous heparin every 12 h (aPTT 55 to 80 s) plus warfarin (INR 2.5 to 3.5) for 1 to 6 months. Operation is advised for nonresponders or patients with mobile thrombi. CONCLUSIONS: Thrombolysis, followed by heparin, warfarin and aspirin, is advised for high risk surgical candidates with left-sided PVT.

Aortic Valve↗
PubMed1997

New frontiers in the management of unstable coronary artery disease.

Thrombotic occlusion is responsible for most acute manifestations of coronary artery disease, including unstable angina and non-Q-wave myocardial infarction. Antiplatelet therapy plays a major role in reducing the risk of ischemic events in such patients. Since thrombin generation is vital to the pathogenesis of thrombosis, recent studies have focused on thrombin inhibition in the management of acute ischemia. Heparin is the most widely used anticoagulant for acute management of thrombosis and is the treatment of choice in preventing and treating venous thromboembolism. Given in therapeutic doses intravenously, it is more effective than aspirin in reducing the risk of death or myocardial infarction in patients with unstable angina. Low-molecular-weight (LMW) heparins have improved pharmacologic and pharmacokinetic properties over standard heparin that may result in greater efficacy and safety. LMW heparins may be given in a fixed dose subcutaneously without monitoring, resulting in greater clinical utility and cost-effectiveness compared with standard heparin. Given subcutaneously in fixed, weight-adjusted doses they are more effective and safer than intravenous heparin in treating deep-vein thrombosis. Several studies have evaluated LMW heparins in unstable angina. In a small open trial, LMW heparin (nadroparin) reduced the risk of acute myocardial infarction compared with aspirin alone or a combination of aspirin and standard heparin. In 2 large clinical trials, LMW heparin (dalteparin) has been shown to be effective in the management of unstable angina with a 63% reduction in risk of death or acute myocardial infarction over patients treated with aspirin alone (Fragmin during Instability in Coronary Artery Disease; FRISC) and to be as effective as intravenous heparin (Fragmin in Unstable Coronary Artery Disease; FRIC).

Angina, Unstable↗
PubMed1997

Fragmin in unstable angina pectoris or in non-Q-wave acute myocardial infarction (the FRIC study). Fragmin in Unstable Coronary Artery Disease.

The safety and efficacy of weight-adjusted, low-molecular-weight heparin (dalteparin) was compared with that of unfractionated heparin during 6 days of treatment in 1,482 patients with unstable angina or non-Q-wave myocardial infarction. Dalteparin, at a lower dose, was compared with placebo during the following 39 days. No significant outcome difference was found between the 2 treatment regimens in the unblinded phase (days 1-6). Between days 6-45 the rates of death, myocardial infarction, and recurrence of angina were comparable between the active treatment and placebo groups. The results suggest that twice-daily administration of subcutaneous dalteparin may be an effective and safe alternative to unfractionated heparin during the acute phase of unstable coronary artery disease. Prolonged treatment with dalteparin at a lower once-daily dose did not confer any additional benefit over aspirin (75-165 mg) alone.

Angina, Unstable↗
PubMed1997

A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group.

BACKGROUND: Antithrombotic therapy with heparin plus aspirin reduces the rate of ischemic events in patients with unstable coronary artery disease. Low-molecular-weight heparin has a more predictable anticoagulant effect than standard unfractionated heparin, is easier to administer, and does not require monitoring. METHODS: In a double-blind, placebo-controlled study, we randomly assigned 3171 patients with angina at rest or non-Q-wave myocardial infarction to receive either 1 mg of enoxaparin (low-molecular-weight heparin) per kilogram of body weight, administered subcutaneously twice daily, or continuous intravenous unfractionated heparin. Therapy was continued for a minimum of 48 hours to a maximum of 8 days, and we collected data on important coronary end points over a period of 30 days. RESULTS: At 14 days the risk of death, myocardial infarction, or recurrent angina was significantly lower in the patients assigned to enoxaparin than in those assigned to unfractionated heparin (16.6 percent vs. 19.8 percent, P=0.019). At 30 days, the risk of this composite end point remained significantly lower in the enoxaparin group (19.8 percent vs. 23.3 percent, P=0.016). The need for revascularization procedures at 30 days was also significantly less frequent in the patients assigned to enoxaparin (27.1 percent vs. 32.2 percent, P=0.001). The 30-day incidence of major bleeding complications was 6.5 percent in the enoxaparin group and 7.0 percent in the unfractionated-heparin group, but the incidence of bleeding overall was significantly higher in the enoxaparin group (18.4 percent vs. 14.2 percent, P=0.001), primarily because of ecchymoses at injection sites. CONCLUSIONS: Antithrombotic therapy with enoxaparin plus aspirin was more effective than unfractionated heparin plus aspirin in reducing the incidence of ischemic events in patients with unstable angina or non-Q-wave myocardial infarction in the early phase. This benefit of enoxaparin was achieved with an increase in minor but not in major bleeding.

Aged↗
PubMed1997

Comparison of low-molecular-weight heparin with unfractionated heparin acutely and with placebo for 6 weeks in the management of unstable coronary artery disease. Fragmin in unstable coronary artery disease study (FRIC)

BACKGROUND: Low-molecular-weight heparin has a number of pharmacological and pharmacokinetic advantages over unfractionated heparin that make it potentially suitable, when used in combination with aspirin, for the treatment of unstable coronary artery disease. METHOD AND RESULTS: Patients with unstable angina or non-Q-wave myocardial infarction (1482) were included in the study, which had two phases. In an open, acute phase (days 1 to 6), patients were assigned either twice-daily weight-adjusted subcutaneous injections of dalteparin (120 i.u./kg) or dose-adjusted intravenous infusion of unfractionated heparin. In the double-blind, prolonged treatment phase (days 6 to 45), patients received subcutaneously either dalteparin (7500 i.u. once daily) or placebo. During the first 6 days, the rate of death, myocardial infarction, or recurrence of angina was 7.6% in the unfractionated heparin-treated patients and 9.3% in the dalteparin-treated patients (relative risk, 1.18; 95% confidence interval [CI], 0.84 to 1.66). The corresponding rates in the two treatment groups for the composite end point of death or myocardial infarction were 3.6% and 3.9%, respectively (relative risk, 1.07; 95% CI, 0.63 to 1.80). Revascularization procedures were undertaken in 5.3% and 4.8% of patients in unfractionated heparin and dalteparin groups, respectively (relative risk, 0.88; 95% CI, 0.57 to 1.35). Between days 6 and 45, the rate of death, myocardial infarction, or recurrence of angina was 12.3% in both the placebo and dalteparin groups (relative risk, 1.01; 95% CI, 0.74 to 1.38). The corresponding rates for death or myocardial infarction were 4.7% and 4.3% (relative risk, 0.92; 95% CI, 0.54 to 1.57). Revascularization procedures were undertaken in 14.2% and 14.3% of patients in the placebo and dalteparin groups, respectively. CONCLUSIONS: Our results add to previous evidence suggesting that the low-molecular-weight heparin dalteparin administered by twice-daily subcutaneous injection may be an alternative to unfractionated heparin in the acute treatment of unstable angina or non-Q-wave myocardial infarction. Prolonged treatment with dalteparin at a lower once-daily dose in our study did not confer any additional benefit over aspirin (75 to 165 mg) alone.

Adult↗
PubMed1997

The use of D-dimer testing and impedance plethysmographic examination in patients with clinical indications of deep vein thrombosis.

OBJECTIVE: To prospectively test the hypothesis that a diagnosis of deep vein thrombosis can be excluded in outpatients who present with clinical indications of deep vein thrombosis and whose results of D-dimer testing and impedance plethysmographic examination on the day of presentation are normal. DESIGN: Prospective cohort study. SETTING: Four university-affiliated hospitals. METHODS: Three hundred ninety-eight consecutive patients with clinical indications of deep vein thrombosis were included in the final analysis. All patients underwent an assessment of pretest probability, bedside D-dimer testing, and impedance plethysmographic examination. In most patients, if the results of D-dimer testing and impedance plethysmographic examination were negative for deep vein thrombosis, anticoagulants were withheld and patients were followed up for 3 months. If the results of one or both tests were abnormal, an examination using venous compression ultrasonography or phlebography was performed. RESULTS: In the majority of patients (69%), the results of D-dimer testing and impedance plethysmographic examination were normal. This combination had a negative predictive value of 98.5% (95% confidence interval, 96.3-99.6) for deep vein thrombosis. CONCLUSION: The results of the D-dimer assay and impedance plethysmographic examination on the day of presentation can be used to treat the majority of outpatients who present with clinical indications of deep vein thrombosis without further testing.

Adult↗
PubMed1997

A comparison of compression ultrasound with color Doppler ultrasound for the diagnosis of symptomless postoperative deep vein thrombosis.

BACKGROUND: Despite advances in primary prophylaxis, venous thromboembolism still occurs in a considerable number of high-risk surgical patients. Screening with conventional ultrasound imaging to detect asymptomatic deep vein thrombosis (DVT) has been suggested as a strategy to improve management of such patients, but it is insufficiently sensitive. We evaluated the ability of color Doppler ultrasound to improve the sensitivity of compression ultrasound in the detection of asymptomatic DVT in high-risk orthopedic patients. METHODS: We prospectively evaluated bilateral compression and color Doppler ultrasound measurements of the entire leg in 204 consecutive patients who underwent elective hip or knee replacement surgery, using contrast venography as the reference test. The sensitivity, specificity, and positive predictive value of the ultrasonography tests were determined. RESULTS: The sensitivity, specificity, and positive predictive value (with 95% confidence intervals [CIs]) of compression ultrasound for the detection of proximal DVT were 60% (39%-81%), 96% (92%-99%), and 71% (48%-89%) respectively. The sensitivity, specificity, and positive predictive value (with 95% CIs) of compression ultrasound for the detection of calf vein thrombosis were 33% (18%-52%), 91% (83%-96%), and 58% (34%-80%), respectively. Color Doppler ultrasonography did not identify any additional proximal or calf vein thrombi to those detected by compression ultrasound alone. The sensitivity for all thrombi was 47% (95% CI, 34%-61%) with a positive predictive value of 65% (95% CI, 48%-79%). CONCLUSIONS: Color Doppler ultrasonography has a moderate to low accuracy for the detection of DVT in patients who have had hip and knee replacement surgery. Color Doppler ultrasonography does not increase the detection rate for asymptomatic DVT over compression ultrasound and thus cannot be recommended as a screening test in this setting.

Hip Prosthesis↗
PubMed1997

Prophylaxis of venous thromboembolism in stroke patients.

Venous thromboembolism is a common complication in patients with acute thrombotic stroke. Estimates of the frequency of deep vein thrombosis (DVT) in untreated patients range from 20 to 75%. This wide range reported depends on the methods used to detect DVT and, importantly, on the degree of lower limb paralysis. Most thrombi occur in the paralyzed limbs in which the frequency ranges from 60 to 75%. Of these thrombi, 25% occur in the proximal segment and present a high risk for pulmonary embolism. Indeed, pulmonary embolism is the third most common cause of death in stroke patients and occurs in 1 to 2% of patients who do not receive prophylaxis. A number of methods of preventing DVT have been shown to be safe and effective in stroke patients. These include low-dose heparin, low-molecular-weight heparin, and a heparinoid. Of these, the data with the heparinoid danaparoid provide the most solid evidence for efficacy, and in comparative trials it has been shown to be more effective than heparin.

Cerebrovascular Disorders↗
PubMed1997

Low-molecular-weight heparins and unstable angina--current perspectives.

Thrombosis is responsible for most acute manifestations of coronary artery disease, including unstable angina and non-Q-wave myocardial infarction (MI). Antiplatelet therapy plays a major role in reducing the risk of ischaemic events in such patients. Since thrombin generation is key in the pathogenesis of thrombosis, recent studies have focussed on thrombin inhibition in the management of acute ischaemia. Heparin is the most widely used anticoagulant for acute management of thrombosis and is the treatment of choice in the prevention and treatment of venous thromboembolism. Heparin given in therapeutic doses intravenously has been shown to be more effective than aspirin at reducing the risk of death or MI in patients with unstable angina. Low-molecular-weight heparins (LMWHs) have improved pharmacologic and pharmacokinetic properties over standard heparin that may result in greater efficiency and safety. LMWH may be given in fixed doses subcutaneously without monitoring, resulting in greater clinical utility and cost-effectiveness compared with standard heparin. A number of LMWHs-dalteparin, enoxaparin and nadroparin-have been evaluated in unstable angina. In a small open trial, nadroparin reduced the risk of ischaemic outcomes compared with aspirin alone or a combination of aspirin and standard heparin. Dalteparin has been evaluated in two large clinical trials in the management of unstable angina. The low-Molecular-Weight Heparin (Fragmin) During Instability in Coronary Artery Disease (FRISC) trial showed that dalteparin resulted in a 63% reduction in risk of death or acute MI compared with aspirin alone. The Fragmin in Unstable Coronary Artery Disease (FRIC) trial showed that dalteparin was as effective as intravenous heparin. Enoxaparin resulted in a statistically significant 16% reduction in the combined outcome of death, MI and recurrence of angina in comparison with standard heparin in the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) trial. There is accumulating evidence that LMWHs are safe and effective alternatives to standard heparin in unstable coronary artery disease and that they offer practical and therapeutic advantages.

Angina, Unstable↗
PubMed1997

Safer anticoagulant therapy after heart valve replacement. Recommendations for less intense regimens.

The use of anticoagulants in patients who undergo heart valve replacement greatly reduces the rate of thromboembolism but increases the risk of bleeding. A number of studies have been done to determine the efficacy of anticoagulation regimens that are less intense than those considered standard. Dr Turpie reviews these and lists the current recommendations of the American College of Chest Physicians.

Anticoagulants↗
PubMed1997

Low-molecular-weight heparin: from the bench to the orthopedic patient.

Standard heparin is widely used for the prevention and treatment of venous thromboembolism; however, it has several limitations including variable dose response, dose-dependent clearance and inhibition of platelet function. To overcome these disadvantages, standard heparin, which is composed of glycosaminoglycans of various molecular weights, has been fractionated into its low-molecular-weight component. Low-molecular-weight heparin (LMWH) exhibits less binding to plasma proteins and endothelial cells than standard heparin resulting in a more predictable dose response profile, a dose-independent mechanism of clearance and a longer plasma half-life. LMWH also has a lower binding affinity for platelets and produces less microvascular bleeding. Evidence from randomized clinical trials demonstrates that LMWH is effective in the prevention of deep vein thrombosis (DVT) in high-risk orthopedic patients. There is also considerable evidence of its efficacy and safety in the initial treatment of proximal DVT. Recent studies have demonstrated the feasibility of home treatment with LMWH, which offers the advantage of greater clinical utility compared with current antithrombotic regimens and hence the possibility of cost savings.

Anticoagulants↗
PubMed1997

Successors to heparin: new antithrombotic agents.

New advances in antithrombotic therapy include low-molecular weight heparins (LMWHs), heparinoids, and direct thrombin inhibitors. LMWHs and heparinoids have improved pharmacologic and pharmacokinetic properties compared with standard, unfractionated heparin. LMWHs are effective in preventing venous thromboembolism in general surgical patients, orthopedic patients, and general medical patients. At equipotent antithrombotic doses, LMWHs produce less bleeding than does unfractionated heparin. When given in fixed doses subcutaneously in the treatment of venous thromboembolic disease, LMWHs have been shown to be as effective as or more effective than and safer than standard heparin given intravenously with regular monitoring. Recent studies have demonstrated that LMWHs are effective in reducing the risk of death and myocardial infarction in patients with unstable angina; they are as effective as intravenous heparin when given subcutaneously without monitoring. Preliminary data indicate that LMWHs also may be effective in improving outcomes in patients with ischemic stroke. The pharmacokinetic characteristics of LMWHs permit their use in a fixed dose administered subcutaneously without monitoring, resulting in greater clinical utility than standard heparin. The direct thrombin inhibitors have a narrow safety window, and in doses that do not produce excessive bleeding have not been shown to have greater efficacy than that of unfractionated heparin.

Clinical Trials as Topic↗