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Biomedical subjects

A G Turpie

Publications and source records attributed to A G Turpie.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1997

Survey of cardiac surgeons' perceptions of the addition of ASA to warfarin for patients with mechanical heart valves.

Evidence suggests that the addition of acetylsalicylic acid (ASA) to warfarin therapy among patients with mechanical heart valves may reduce mortality, at a slightly higher bleeding risk. A survey was conducted of North American cardiac surgeons to assess whether they routinely use ASA in conjunction with anticoagulants among such patients. From a list of 142 cardiac surgeons and centres, questionnaires were successfully transmitted by fax to 137. Respondents were surveyed about their prescribing habits of both warfarin and ASA among patients with mechanical heart valves. Information collected included the target international normalized ratio (INR) and reasons for not routinely prescribing ASA, when applicable. One hundred and eighteen cardiac surgeons (86%) returned the questionnaire: 75% were American and 25% Canadian. All surgeons (100%) stated that they use warfarin for patients with mechanical valves, but there was little consensus about the target INR. Only 25 respondents (21%) routinely used ASA in conjunction with anticoagulants, while 90 (76%) said they would not. The most common reason cited for withholding ASA was the perceived increased risk of bleeding (49% of nonusers), while another 23% felt that there is no benefit. Of the 90 surgeons who would not routinely prescribe ASA, 50 (55%) would on occasion. The most commonly used dose of ASA was 80 to 100 mg daily (79%). Low dose ASA, in conjunction with warfarin, is underused by North American cardiac surgeons for the prevention of systemic thromboembolism among patients with mechanical heart valves. Most surgeons avoid ASA out of concern for the increased risk of hemorrhage and a belief that there is no benefit. These perceptions are not supported by recent scientific data, however.

Anticoagulants↗
PubMed1996

Comparison of high-dose with low-dose aspirin in patients with mechanical heart valve replacement treated with oral anticoagulant.

BACKGROUND: There are no reported studies on the safety and efficacy of low-dose aspirin with low-intensity oral anticoagulation in patients with heart valve replacement. In this study, we compared the use of 100 mg/d aspirin with 650 mg/d aspirin in the prevention of systemic embolism and vascular death in patients with heart valve replacement who were being treated with oral anticoagulants with a target international normalized ratio (INR) of 2.0 to 3.0. METHODS AND RESULTS: Four hundred nine of 416 consecutive patients who had cardiac valve replacement were randomized in open allocation into one of two groups; both groups were treated with oral anticoagulant therapy with a target INR of 2.0 to 3.0. Two hundred seven patients who received 100 mg/d aspirin for an average of 24.1 months were compared with 202 patients who received 650 mg/d aspirin for an average of 21.7 months in a randomized-treatment, open-allocation study. There were no significant differences in systemic embolism, vascular death, or total death rates between the low- and high-dose aspirin treatment groups (0.5 and 1.1, 1.2 and 0.5, and 4.6 and 2.5 per 100 patients/y, respectively). The total number of hemorrhagic events was 13.4 per 100 patients/y in the high-dose aspirin group and 7.9 per 100 patients/y in the low-dose aspirin group (P = .035), but the rate of bleeding was influenced by dipyridamole in the 650-mg aspirin group. CONCLUSIONS: In patients with mechanical heart valve replacements, low-dose aspirin (100 mg/d) in conjunction with oral anticoagulants at an INR of 2.0 to 3.0 is as effective as the use of high-dose aspirin (650 mg/d) in the prevention of systemic embolism.

Administration, Oral↗
PubMed1996

Ardeparin (low-molecular-weight heparin) vs graduated compression stockings for the prevention of venous thromboembolism. A randomized trial in patients undergoing knee surgery.

BACKGROUND: Deep vein thrombosis is common in patients undergoing major knee surgery. Static graduated compression stockings effectively prevent venous thrombosis in general surgery. Because of the demonstrated prophylactic efficacy of pneumatic compression in knee surgery, the similar efficacy of static graduated compression and pneumatic compression in neurosurgery, and the easier use of static graduated compression in knee surgery, graduated static compression stockings were used as the control arm in our clinical trial. Although low-molecular-weight heparin had been shown to be effective in general surgery and hip replacement, its efficacy was unproved in knee surgery. METHODS: A double-blind, randomized trial compared the combination of low-molecular-weight heparin and graduated compression stockings with graduated compression stockings alone in patients undergoing major knee surgery. Patients received either ardeparin (Normiflo) (low-molecular-weight heparin), 0.005 mL/kg (50 anti-Xa U/Kg), or placebo. Both were administered subcutaneously twice daily commencing 12 to 24 hours after surgery and continued for 14 days or until discharge, if sooner. Both study groups wore graduated compression stockings. Bilateral venography was performed on day 14, or sooner if the patient was ready for discharge. RESULTS: One hundred twenty-two patients were allocated to receive ardeparin and 124 received placebo. Ninety-six patients in the ardeparin group and 103 in the placebo group had evaluable venograms. Deep vein thrombosis was detected in 28 patients in the ardeparin group and in 60 in the placebo group. Proximal deep vein thrombosis was detected in two patients who received ardeparin and 16 who received placebo. One patient in each group, both of whom did not have venography, experienced pulmonary embolism. Thus, deep vein thrombosis or pulmonary embolism was detected in 29 (29.9%) of the 97 patients in the ardeparin group and in 61 (58.7%) of the 104 patients in the placebo group, a relative risk reduction of 49% (P < 00.1). The rate of major bleeding in the ardeparin group was 2.5%, compared with 2.4% in the placebo group. CONCLUSION: Ardeparin administered postoperatively twice daily is effective and safe for the prevention of venous thrombosis in patients undergoing major knee surgery. Whereas graduated compression stockings have been shown to be effective prophylactic agents in general surgery and neurosurgery, they have little effect in knee surgery.

Aged↗
PubMed1996

A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis.

BACKGROUND: Patients with acute proximal deep-vein thrombosis are usually treated first in the hospital with intravenous standard (unfractionated) heparin. However, the longer plasma half-life, better bioavailability after subcutaneous administration, and more predictable anticoagulant response of low-molecular-weight heparins make them attractive for possible home use. We compared these two approaches. METHODS: Patients with acute proximal deep-vein thrombosis were randomly assigned to receive either intravenous standard heparin in the hospital (253 patients) or low-molecular-weight heparin (1 mg of enoxaparin per kilogram of body weight subcutaneously twice daily) administered primarily at home (247 patients). The study design allowed outpatients taking low-molecular-weight heparin to go home immediately and hospitalized patients taking low-molecular-weight heparin to be discharged early. All the patients received warfarin starting on the second day. RESULTS: Thirteen of the 247 patients receiving low-molecular-weight heparin (5.3 percent) had recurrent thromboembolism, as compared with 17 of the 253 patients receiving standard heparin (6.7 percent; P=0.57; absolute difference, 1.4 percentage points; 95 percent confidence interval, -3.0 to 5.7). Five patients receiving low-molecular-weight heparin had major bleeding, as compared with three patients receiving standard heparin. After randomization, the patients who received low-molecular-weight heparin spent a mean of 1.1 days in the hospital, as compared with 6.5 days for the standard-heparin group; 120 patients in the low-molecular-weight- heparin group did not need to be hospitalized at all. CONCLUSIONS: Low-molecular-weight heparin can be used safely and effectively to treat patients with proximal deep-vein thrombosis at home.

Aged↗
PubMed1996

Low-molecular-weight heparinoid orgaran is more effective than aspirin in the prevention of venous thromboembolism after surgery for hip fracture.

BACKGROUND: The study objective was to determine the relative efficacy and safety of a low-molecular-weight heparinoid (Orgaran) compared with aspirin for the prevention of postoperative venous thromboembolism in patients undergoing surgery for fractured hips. A double-blind, randomized, controlled trial was used to study 251 consecutive eligible and consenting patients undergoing surgery for hip fracture in seven participating hospitals. METHODS AND RESULTS: Patients received either fixed-dose Orgaran by subcutaneous injection every 12 hours in a dose of 750 anti-Factor Xa units or aspirin 100 mg orally twice daily; both regimens were started 12 to 24 hours after surgery and continued for 14 days or until discharge, if sooner. All patients had postoperative 125I-fibrinogen leg scanning and impedance plethysmography. If the results of one or both tests were positive, then venography was performed. Otherwise, venography was done at day 14, or sooner if the patient was ready for discharge. Pulmonary embolism in symptomatic patients was diagnosed on the basis of a high probability perfusion/ventilation lung scan, a positive angiogram, or a clinically significant embolism detected at autopsy. Evaluable venograms were obtained in 90 of the 125 patients randomly assigned to receive Orgaran and in 87 of the 126 patients assigned to receive aspirin. Venous thromboembolism was detected in 25 (27.8%) patients in the Orgaran group and in 39 (44.3%) patients in the aspirin group. Thus, there was a relative risk reduction of 37% with Orgaran (P=.028; 95% confidence interval, 3.7% to 59.7%). Six (6.8%) of 88 patients in the Orgaran group and 12 (14.3%) of 84 patients in the aspirin group developed proximal deep vein thrombosis or pulmonary embolism, a relative risk reduction of 52% with Orgaran (P=.137; 95% confidence interval, -30.7% to 84.6%). Hemorrhagic complications occurred in 2 (1.6%) patients given Orgaran and 8 (6.4%) patients given aspirin (P=.10). There was one major bleed in the Orgaran group compared with four in the aspirin group. CONCLUSIONS: This study demonstrates that Orgaran is significantly more efficacious than aspirin in preventing postoperative venous thromboembolism in patients undergoing surgery for fractured hips, with no evidence of any increase in hemorrhagic complications.

Administration, Oral↗
PubMed1996

Mechanical valves.

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Anticoagulants↗