Antithrombotic therapy in patients with mechanical and biological prosthetic heart valves.
Explore the source record for details and available documents.
Anticoagulants↗
Biomedical subjects
A G Turpie
Publications and source records attributed to A G Turpie.
Antithrombotic therapy in patients with saphenous vein and internal mammary artery bypass grafts following percutaneous transluminal coronary angioplasty.
Explore the source record for details and available documents.
Angioplasty, Balloon, Coronary↗
Prevention of deep vein thrombosis after elective hip surgery. A randomized trial comparing low molecular weight heparin with standard unfractionated heparin.
OBJECTIVE: To determine the relative efficacy and safety of low molecular weight (LMW) heparin (Enoxaparin) compared with standard calcium heparin for the prevention of postoperative deep vein thrombosis in patients undergoing elective hip surgery. DESIGN: A double-blind, randomized, controlled trial. PATIENTS: Six hundred sixty-five consecutive patients undergoing hip replacement at five participating hospitals. INTERVENTIONS: Patients received either fixed-dose LMW heparin, 30 mg subcutaneously twice daily, or fixed-dose standard calcium heparin, 7500 units subcutaneously twice daily; both regimens were started 12 to 24 hours after surgery and continued for 14 days or until discharge if sooner. MEASUREMENTS: All patients had postoperative I-125-fibrinogen leg scanning and impedance plethysmography. If results of one or both tests were positive, then venography was done. Otherwise, venography was done between day 10 and day 14, or sooner if the patient was ready for discharge. RESULTS: Evaluable venograms were obtained in 258 of the 333 patients randomly assigned to receive LMW heparin and in 263 of the 332 patients assigned to receive calcium heparin. For patients with evaluable venograms, thrombosis was detected in 50 patients (19.4%) who received LMW heparin compared with 61 patients (23.2%) who received standard heparin (difference, -3.8%; 95% CI, -11.1% to 3.6%) (P greater than 0.2). Proximal deep vein thrombosis was detected in 5.4% of the patients receiving LMW heparin and in 6.5% of the patients receiving standard heparin (difference, -1.1%; CI, - 5.2% to 3.3%) (P greater than 0.2). For the entire group of 665 patients, venous thrombosis occurred in 17.1% given LMW heparin and in 19.0% given standard heparin. Hemorrhagic complications occurred in 31 patients (9.3%) given standard heparin and in 17 patients (5.1%) given LMW heparin (difference, 4.2%; CI, 0.3% to 8.2%) (P = 0.035). The relative risk reduction was 45%. The rate of major bleeding in the standard heparin group was 5.7% compared with 3.3% in the LMW heparin group (difference, 2.4%; CI, -1.0% to 5.4%) (P = 0.13). The relative risk reduction was 42%. CONCLUSION: Low molecular weight heparin is significantly less hemorrhagic than standard unfractionated heparin; the difference in the rate of deep vein thrombosis, although not statistically significant (P greater than 0.2), favors the use of LMW heparin.
Adult↗
Efficacy of a postoperative regimen of enoxaparin in deep vein thrombosis prophylaxis.
Venous thromboembolism is a common complication in patients undergoing elective hip replacement, in whom the incidence of calf vein thrombosis is 40% to 60%; proximal vein thrombosis, 20%; and fatal pulmonary embolism, 1% to 2% when prophylaxis is not used. A double-blind, randomized trial comparing low-molecular-weight heparin (enoxaparin) with placebo for the prevention of venous thrombosis in patients undergoing elective hip surgery was carried out. Prophylactic treatment with a fixed dose was begun postoperatively and continued for 14 days. Fifty patients in each treatment group underwent surveillance with 125I-fibrinogen leg scanning and impedance plethysmography. In the first 24 patients, venography was performed only if their surveillance test was positive. Venography was requested in the remaining 76 patients even if the screening tests were negative; in this latter group, venous thrombosis occurred in 4 patients (10.8%) given enoxaparin and 20 patients (51.3%) given placebo (p = 0.0002). The corresponding rates for proximal vein thrombosis were 5.4% and 23.1%, respectively (p = 0.029). In the entire group of 100 patients, venous thrombosis occurred in 12% of those given enoxaparin and 42% of those given placebo (p = 0.0007). The corresponding rates for proximal vein thrombi were 4% and 20%, respectively (p = 0.014). The observed hemorrhagic rate was 5% in each treatment group. The results of this study show that prophylaxis with fixed-dose enoxaparin is effective and safe for patients undergoing elective hip replacement.
Heparin, Low-Molecular-Weight↗
Anticoagulant therapy after acute myocardial infarction.
The use of anticoagulant therapy for patients who have had an acute myocardial infarction is still controversial, mainly because early major studies had conflicting findings, but reanalysis of the data did produce evidence that anticoagulation had clinically and statistically significant benefits. Now more evidence, including the results of a 10-day in-hospital study of low- and high-dose calcium heparin, has been gathered to support using anticoagulants for these patients. The study used the development of left ventricular mural thrombosis, a frequent complication of acute myocardial infarction that carries a high risk for systemic embolic complications, to assess clinical outcome: A reduced incidence of mural thrombosis would be taken to indicate reduced chances that patients would have major systemic emboli. Two-dimensional echocardiography was used to detect thrombi. In the study, the incidence of left ventricular mural thrombosis was significantly lower in the high--than in the low-dose group. Among patients in the high-dose group in whom a mural thrombosis did develop, plasma heparin concentrations were significantly lower and activated partial thromboplastin times were shorter. These data suggest that monitoring plasma heparin levels and anticoagulant response can ensure maximal treatment effectiveness. No significant differences in other outcomes--such as bleeding complications, nonhemorrhagic strokes and mortality--were found between the high- and low-dose treatment groups.
Cause of Death↗
Antithrombotic treatment of cerebrovascular disease.
The most common type of cerebrovascular disease is ischaemia or infarction from atherothrombosis or cardiac embolism. Antithrombotic treatment with an antiplatelet agent or anticoagulant assumes a prior clinical classification into categories of transient ischaemic attack (TIA) or minor stroke, acute partial stable stroke, stroke-in-progression, and completed stroke. Aspirin reduces the risk of stroke, myocardial infarction, and death after TIA or minor stroke secondary to atherothrombosis. Aspirin is effective in both sexes at a dose of 300 or 1200 mg/day. Ticlopidine (500 mg/day), a new antiplatelet agent, is more effective than aspirin in preventing stroke and death in patients with TIA or minor stroke. Ticlopidine (500 mg/day) is effective in preventing recurrent stroke, myocardial infarction, or vascular death in patients with completed stroke. Aspirin has not been directly shown to be effective after completed stroke. No clear evidence exists for the use of anticoagulants in atherothrombotic cerebral vascular disease in patients presenting with TIA or minor stroke, acute partial stable stroke, stroke-in-progression, or completed stroke. Anticoagulation for rheumatic valvular heart disease is effective in preventing recurrent embolism. Long-term anticoagulation of patients with mechanical prosthetic valves protects against initial embolism and prevents recurrent embolism. The addition of aspirin (500-1000 mg/day) to warfarin reduces the rate of cerebral embolism from mechanical prosthetic heart valves but is associated with increased bleeding. The addition of dipyridamole (400 mg/day) to warfarin may be more effective than aspirin in reducing the rate of cerebral embolism from mechanical prosthetic heart valves and has fewer bleeding side-effects. Anticoagulation during the hospital phase of myocardial infarction reduces the incidence of systemic embolism/stroke. Long-term anticoagulation of patients after the hospital phase of myocardial infarction reduces the incidence of systemic embolism/stroke, recurrent myocardial infarction and death. Prophylactic anticoagulant treatment of patients with non-valvular atrial fibrillation reduces the incidence of embolism, but the optimal duration of treatment is not known. Immediate anticoagulation of patients with completed cardioembolic stroke is safe and effective in preventing recurrent embolism.
Anticoagulants↗
A new short infusion dosage regimen of recombinant tissue plasminogen activator in patients with venous thromboembolic disease.
Although recombinant tissue-type plasminogen activator (rt-PA) has the potential to induce thrombolysis without producing a generalized coagulopathy, the dosage regimens in present use induce a plasma fibrinolytic state and are associated with bleeding. Animal experiments have demonstrated that rt-PA produces continuing thrombolysis after it is cleared from the circulation and that thrombolysis is increased and bleeding is reduced when rt-PA is administered over a short time period. To determine whether a short course regimen of rt-PA has potential in man, we gave a bolus injection of rt-PA (0.6 mg/kg) concurrently with heparin to five patients with venous thromboembolism. Three patients with angiographically proven pulmonary embolism had marked improvement of the perfusion defects when lung scans were repeated 24 h after rt-PA administration. In one of two patients with thrombosis of the deep veins of the upper extremity the venographic defect resolved completely. In three of four patients there was a mild decrease in fibrinogen and a moderate decrease in alpha 2-antiplasmin levels. There was no excessive bleeding. These results suggest that a bolus injection regimen of rt-PA has considerable potential in the treatment of thromboembolic disease.
Axillary Vein↗
A randomized trial of a single bolus dosage regimen of recombinant tissue plasminogen activator in patients with acute pulmonary embolism.
Experiments in animals have demonstrated that recombinant tissue plasminogen activator (rt-PA) produces continuing thrombolysis after it is cleared from the circulation and that thrombolysis is both increased and accelerated, and bleeding is reduced when rt-PA is administered over a short period. In previous studies in patients with thrombotic disease, rt-PA has been shown to be an effective thrombolytic agent when administered by continuous infusion over a period between 90 minutes and 8 hours. To determine whether a short course regimen of rt-PA can achieve thrombolysis, a double-blind randomized trial has been conducted in which patients with objectively established acute symptomatic pulmonary embolism who were receiving heparin were allocated to either a 2-minute infusion of rt-PA at a dose of 0.6 mg/kg (33 patients) or saline placebo (25 patients). Perfusion lung scanning was used to assess the change in pulmonary perfusion at 24 hours and seven days post-study drug administration. Thirty-four percent of the rt-PA patients had a greater than 50 percent resolution in the perfusion defect at 24 hours compared to 12 percent of placebo patients (p = 0.026). At 24 hours, the mean relative improvement in the perfusion defect was 37.0 percent in rt-PA treated patients compared to 18.8 percent in the placebo group (p = 0.017). By day 7, no difference in lung scan resolution was detected between the groups. There were no major bleeds in either group nor were there any differences in transfusion requirements between groups. Minor bleeding occurred in 15 of the rt-PA patients mainly at angiogram-catheter insertion and venipuncture sites. These results suggest that a bolus regimen of rt-PA produces accelerated thrombolysis and provides an alternative and convenient approach to thrombolytic therapy in patients with pulmonary embolism.
Acute Disease↗
Enoxaparin prophylaxis in elective hip surgery.
A randomized double-blind placebo-controlled trial to determine the efficacy and safety of enoxaparin for the prevention of deep vein thrombosis in patients undergoing elective hip surgery was performed. Prophylaxis, with enoxaparin in a dose of 30 mg subcutaneously twice daily, was begun post-operatively and continued for 14 days. Deep vein thrombosis occurred in 6 (12%) of 50 patients in the enoxaparin group and 21 (42%) of 50 patients in the placebo group (p = 0.0007). Proximal vein thrombosis occurred in two (4%) of the enoxaparin group and 10 (20%) of the placebo group (p = 0.014). Two patients in the placebo group and two in the enoxaparin group developed haemorrhagic complications. This study indicates that fixed-dose enoxaparin begun post-operatively is effective and safe for the prevention of deep vein thrombosis in patients undergoing elective hip replacement.
Aged↗
Tissue plasminogen activator (rt-PA) vs heparin in deep vein thrombosis. Results of a randomized trial.
We performed a randomized trial comparing two dosing regimens of recombinant tissue plasminogen activator (rt-PA) plus heparin vs heparin alone in the treatment of acute proximal deep vein thrombosis in 83 patients. Of 12 patients who received 0.5 mg/kg rt-PA plus heparin over 4 h, seven (58 percent) had greater than 50 percent lysis of the thrombus, compared with none of 12 who received placebo plus heparin (p = 0.002). Of 28 patients who received 0.5 mg/kg rt-PA over 8 h, repeated in 24 h, six (21 percent) had greater than 50 percent lysis, compared with two (7 percent) of 30 patients who received placebo plus heparin (p = 0.11). The 4-h infusion of rt-PA produced a 40 percent reduction and the 8-h infusion an 11 percent reduction in plasma fibrinogen concentration. At long-term follow-up, three (25 percent) of 12 patients in whom greater than 50 percent lysis was achieved had symptoms of the postphlebitic syndrome, compared with 19 (56 percent) of 34 patients in whom lysis was less than 50 percent (p = 0.07).
Double-Blind Method↗
An evaluation of impedance plethysmography and 125I-fibrinogen leg scanning in patients following hip surgery.
Venous thromboembolism is a common post-operative complication in patients following hip surgery. 125I-fibrinogen leg scanning and impedance plethysmography (IPG), are often used in the detection of venous thrombi in such patients. Information on the sensitivity and specificity of these non-invasive tests for the diagnosis of venous thrombosis following hip surgery is relevant for both patient management and for choosing the appropriate outcome measure for clinical trials evaluating new prophylactic regimens. We determined the sensitivity and specificity of the IPG alone, the 125I-fibrinogen leg scan alone, as well as the combined use of the two tests from a retrospective analysis of 685 hip surgery patients who participated in clinical trials of anti-thrombotic prophylaxis. These patients were followed prospectively with non-invasive tests. Bilateral venography was attempted either when one or both screening tests became positive or on day 10-14 post-operatively if both screening tests remained negative. Adequate venography was obtained in 1,010 (73.7%) legs and thrombi were identified in 198 (19.6%) legs. The sensitivities of the IPG and leg scanning were 12.9% and 44.6% respectively; the corresponding specificities were 98.1% and 95.0%. The sensitivity of a positive result on one or both screening tests was 49.6% with a specificity of 93.9%. Therefore, leg scanning and IPG, even in combination, are not sufficiently accurate to be recommended as the only strategy for the diagnosis of venous thrombosis following hip surgery. Venography should be considered in all patients undergoing surveillance testing either when one or both of the screening tests become positive or on day 10-14 if the screening tests remain negative.
Fibrinogen↗
Prevention of left ventricular mural thrombus.
Acute myocardial infarction is associated with a high incidence of left ventricular mural thrombosis, which causes most of the systemic emboli. A double-blind trial was undertaken in patients with anterior transmural myocardial infarction to evaluate the ability of a high-dose heparin regimen to prevent left ventricular mural thrombosis. The high dose consisted of 12,500 U of calcium heparin subcutaneously every 12 hours for 10 days, which was compared with a low dose consisting of 5,000 U every 12 hours. The formation of left ventricular mural thrombosis was assessed by means of 2-dimensional echocardiography on day 10 after infarction. The high-dose group had a significantly lower incidence of left ventricular mural thrombosis than did the low-dose group. This was achieved without increasing the incidence of bleeding. The benefits of high-dose heparin were associated with maintaining plasma heparin concentrations at 0.2 U/ml and activated partial thromboplastin time between 50 and 60 seconds.
Double-Blind Method↗
The Canadian American Ticlopidine Study (CATS) in thromboembolic stroke.
The Canadian American Ticlopidine Study (CATS) is a randomised, double-blind, placebo-controlled trial to assess the effect of ticlopidine (250 mg twice daily) in reducing the rate of subsequent occurrence of stroke, myocardial infarction, or vascular death in patients who have had a recent thromboembolic stroke. Twenty-five centres entered 1072 patients into the study between 1 week and 4 months after their qualifying stroke. The patients were treated and followed for up to 3 years (mean 24 months). In the efficacy analysis, the event rate per year for stroke, myocardial infarction or vascular death, considered together, was 15.3% in the placebo group and 10.8% in the ticlopidine group, representing a relative risk reduction with ticlopidine of 30.2% (95% confidence interval 7.5-48.3%; p = 0.006). Ticlopidine was beneficial for both men and women (relative risk reductions 28.1%, p = 0.037, and 34.2%, p = 0.045, respectively). Analysis by intention-to-treat gave a smaller estimate of risk reduction (23.3%, p = 0.020) for stroke, myocardial infarction, or vascular death. Adverse experiences associated with ticlopidine included neutropenia (severe in about 1% of cases) and skin rash and diarrhoea (severe in 2% of cases each); all were reversible. This study provides evidence of a beneficial effect of ticlopidine in both men and women with a recent thromboembolic stroke.
Aged↗
Comparison of high-dose with low-dose subcutaneous heparin to prevent left ventricular mural thrombosis in patients with acute transmural anterior myocardial infarction.
We performed a double-blind randomized trial comparing high doses of subcutaneous heparin (12,500 units every 12 hours) with low doses (5000 units every 12 hours) for 10 days in the prevention of left ventricular mural thrombosis in 221 patients with acute anterior myocardial infarction. Left ventricular mural thrombosis was observed by two-dimensional echocardiography on the 10th day after infarction in 10 of 95 patients (11 percent) in the high-dose group and in 28 of 88 patients (32 percent) in the low-dose group (P = 0.0004). One patient in the high-dose group and four in the low-dose group had nonhemorrhagic strokes (P = 0.17). One patient in the low-dose group had a fatal pulmonary embolism. There was no difference in the frequency of hemorrhagic complications, which occurred in six patients in the high-dose group and four in the low-dose group. The mean (+/- SEM) plasma heparin concentration was 0.18 +/- 0.017 U per milliliter in the high-dose group and 0.01 +/- 0.005 U per milliliter in the low-dose group (P less than 0.0001). In the high-dose group, the mean plasma heparin concentration was 0.10 +/- 0.029 U per milliliter among patients with abnormal two-dimensional echocardiograms, as compared with 0.19 +/- 0.019 U per milliliter among patients with normal echocardiograms (P = 0.01). We conclude that heparin administered subcutaneously in a dosage of 12,500 units every 12 hours to patients with acute anterior transmural myocardial infarction is more effective than a lower dosage (5000 units every 12 hours) in preventing left ventricular mural thrombosis.
Aged↗
Heparin in the treatment of thromboembolic stroke.
Explore the source record for details and available documents.
Clinical Trials as Topic↗
The relationship between ex vivo anti-factor Xa levels and efficacy/safety of low molecular weight heparin.
Explore the source record for details and available documents.
Factor Xa Inhibitors↗
Prevention of deep vein thrombosis in potential neurosurgical patients. A randomized trial comparing graduated compression stockings alone or graduated compression stockings plus intermittent pneumatic compression with control.
In a randomized trial of neurosurgical patients, groups wearing graduated compression stockings alone (group 1) or graduated compression stockings plus intermittent pneumatic compression (IPC) (group 2) were compared with an untreated control group in the prevention of deep vein thrombosis (DVT). In both active treatment groups, the graduated compression stockings were continued for 14 days or until hospital discharge, if earlier. In group 2, IPC was continued for seven days. All patients underwent DVT surveillance with iodine 125-labeled fibrinogen leg scanning and impedance plethysmography. Venography was carried out if either test became abnormal. Deep vein thrombosis occurred in seven (8.8%) of 80 patients in group 1, in seven (9.0%) of 78 patients in group 2, and in 16 (19.8%) of 81 patients in the control group. The observed differences among these rates are statistically significant. The results of this study indicate that graduated compression stockings alone or in combination with IPC are effective methods of preventing DVT in neurosurgical patients.
Clinical Trials as Topic↗
A randomized trial of less intense postoperative warfarin or aspirin therapy in the prevention of venous thromboembolism after surgery for fractured hip.
A randomized trial was carried out with 194 patients to compare the effectiveness of sodium warfarin or aspirin with that of placebo in the prevention of venous thromboembolism after surgery for fractured hip. Prophylaxis was commenced postoperatively and continued for 21 days or until patient discharge, whichever was earlier. All patients underwent surveillance with iodine 125-fibrinogen leg scanning and impedance plethysmography, with subsequent venography. Venous thromboembolism occurred in 13 patients (20.0%) in the warfarin group, 27 patients (40.9%) in the aspirin group, and 29 patients (46.0%) in the placebo group. Proximal vein thrombosis or pulmonary embolism occurred in 6 patients (9.2%) in the warfarin group, 7 patients (10.6%) in the aspirin group, and 19 patients (30.2%) in the placebo group. The results of this study show that sodium warfarin therapy is safe and effective in preventing thromboembolic complications in patients undergoing surgery for fractured hip, and that aspirin therapy is an equally safe and effective method for preventing proximal vein thrombosis or pulmonary embolism.
Adult↗