Low molecular weight heparin and unfractionated heparin for prevention of thrombo-embolism in general surgery: a meta-analysis of randomised clinical trials

Low molecular weight heparin (LMWH), unfractionated heparin (UFH) and warfarin were compared with respect to efficacy and safety in the prevention of thrombo-embolism in general surgery. Meta-analysis (MA) with a priori definition of the MA protocol was used to combine the results from randomised trials with patients who underwent general surgery and deep-vein thrombosis (DVT) prophylaxis with LMWH, UFH or warfarin. Forty-four studies were identified for assessment and 33 were included, however, none for warfarin. For efficacy (DVT and pulmonary embolism) and major bleeding, no significant difference between the LMWH- and UFH-treated groups was demonstrated. The relative risk of minor bleedings for LMWH versus UFH was 0.75 (0.64-0.88; 95% confidence interval) and is significant (p < 0.05). Within the limitations of the MA, LMWH and UFH did not differ significantly in terms of prevention of thrombo-embolism, but LMWH had a significantly better safety profile. On this basis, LMWH may be preferable to UFH in the prevention of thrombo-embolism in general surgery.     

A phase II study of paclitaxel in heavily pretreated patients with small-cell lung cancer

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are major complications associated with total knee arthroplasty. The American College of Chest Physicians recommends twice-daily, fixed-dose low-molecular-weight heparin (LMWH) as routine prophylaxis in this patient population. This study represents a cost analysis of ardeparin and enoxaparin, the two LMWHs currently available for this indication in the United States. Costs for treating DVT, PE, and major bleeding episodes were derived from values reported in the literature. Both ardeparin and enoxaparin were found to produce significant cost savings when used routinely as DVT prophylaxis after knee replacement surgery compared with no prophylaxis. Based on the currently available data, enoxaparin 40 mg once daily appears to be the least costly LMWH for routine pharmacoprophylaxis of DVT in patients undergoing knee replacement surgery.     

Low molecular weight heparin: a critical analysis of clinical trials

LMWHs are an important new class of antithrombotic agents. They differ from UFH in having relatively more anti-Xa activity, greater bioavailability at low doses, longer half-life, and more predictable anticoagulant response when administered in fixed doses. These properties allow LMWHs to be administered QD or at most BID and without laboratory monitoring. The incidence of heparin-induced thrombocytopenia also appears to be lower with an LMWH than with heparin. Given their favorable pharmacological profile, it was of interest to critically appraise clinical trials of thromboprophylaxis and treatment with these new agents. In orthopedic trials, it was noted that LMWH provided safe and effective thromboprophylaxis for patients undergoing major orthopedic surgery of the lower limb. In those having hip arthroplasty, LMWH was as effective as low-intensity warfarin therapy, but its use was associated with more wound hematomas. In those having total knee arthroplasty, LMWH was more effective than warfarin and did not increase bleeding. However, the prevalence of DVTs complicating this procedure as well as acute hip fracture remains unacceptably high, and additional studies of LMWH in combination with other prophylactic methods, such as external pneumatic compression, are needed. Only one adequately designed trial found less bleeding resulted from LMWH prophylaxis administered at an equivalent antithrombotic dose to UFH. In general medical patients, LMWH appeared to be as effective as UFH and had the advantages of less frequent injections and fewer injection site hematomas. In general surgical patients, there was a lower risk of thromboembolism but a trend toward an increase in bleeding events. Subjects with strokes and spinal cord injuries benefited from fewer thrombotic events, and the latter had fewer bleeding complications. Other potential indications for LMWH, such as cardiopulmonary bypass, hemodialysis, and preservation of graft patency, are presently under study. Perhaps the most impressive benefits of LMWH will be realized when it is used for the treatment of venous thromboembolism. The meta-analysis presented in this review showed a trend toward greater efficacy with LMWH and fewer major bleeding events in comparison with adjusted-dose intravenous UFH. Also, during the months following the thrombotic event, there was significantly less mortality in patients receiving LMWH. A further advantage was the subcutaneous route of administration and lack of requirement for laboratory monitoring. Additional treatment trials are presently in progress and may establish LMWH as the treatment of choice for patients with thromboembolic disorders.     

Meta-analysis of effectiveness of intermittent pneumatic compression devices with a comparison of thigh-high to knee-high sleeves

This meta-analysis used all original articles from 1966 to June 1996 that fit the preset inclusion criteria to examine the clinical effectiveness of intermittent pneumatic compression (IPC) devices in preventing deep vein thrombosis (DVT) and pulmonary embolism and to compare the results of knee-high sleeves to thigh-high sleeves. IPC devices decreased the relative risk of DVT by 62 per cent when compared with placebo, 47 per cent compared with graduated compression stockings, and 48 per cent compared with mini-dose heparin. IPC devices significantly decreased the relative risk of DVT compared with placebo in high-risk patients such as neurosurgery and major orthopedic surgery patients and in modest risk patients such as general surgery patients. In major orthopedic surgery patients, the incidence of DVT was similar for IPC- and warfarin-treated patients; however, IPC was significantly better than warfarin at decreasing the incidence of calf only DVT, whereas warfarin seemed to be better at decreasing proximal DVT. IPC devices are effective in decreasing the incidence of DVT in patients at moderate to high risk and are probably more efficacious than graduated compression stockings or mini-dose heparin; however, IPC devices are not protective against pulmonary embolism. The data directly comparing the various methods of compression (knee-high versus thigh-high sleeves and graded-sequential versus uniform compression) are sparse and conflicting.     

Incidence and characteristics of fall-related emergency department visits

BACKGROUND: Patients with acute ischemic syndromes (AIS) suffer high rates of recurrent ischemic events despite aspirin treatment. Long-term therapy with oral anticoagulants in addition to aspirin may reduce this risk. We studied the effects of long-term warfarin at 2 intensities in patients with AIS without ST elevation in 2 consecutive randomized controlled studies. METHODS AND RESULTS: In phase 1, after the cessation of 3 days of intravenous antithrombotic therapy, 309 patients were randomized to receive fixed low-dose (3 mg/d) warfarin for 6 months that produced a mean international normalized ratio (INR) of 1.5+/-0.6 or to standard therapy. Eighty-seven percent of patients received aspirin in both groups. The rates of cardiovascular (CV) death, new myocardial infarction (MI), and refractory angina at 6 months were 6.5% in the warfarin group and 3.9% in the standard therapy group (relative risk [RR], 1. 66; 95% CI, 0.62 to 4.44; P=0.31). The rates of death, new MI, and stroke were 6.5% in the warfarin group and 2.6% in the standard therapy group (RR, 2.48; 95% CI, 0.80 to 7.75; P=0.10). The overall rate of rehospitalization for unstable angina was 21% and did not differ significantly between the groups. Four patients in the warfarin group (2.6%) and none in the control group experienced a major bleed (RR, 2.48; 95% CI, 0.80 to 7.75), and there was a significant excess of minor bleeds in the warfarin group (14.2% versus 2.6%; RR, 5.46; 95% CI, 1.93 to 15.5; P=0.001). In phase 2, the protocol was modified, and 197 patients were randomized <48 hours from the onset of symptoms to receive warfarin at an adjusted dose that produced a mean INR of 2.3+/-0.6 or standard therapy for 3 months. Eighty-five percent received aspirin in both groups. The rates of CV death, new MI, and refractory angina at 3 months were 5. 1% in the warfarin group and 12.1% in the standard group (RR, 0.42; 95% CI, 0.15 to 1.15; P=0.08). The rates of all death, new MI, and stroke were 5.1% in the warfarin group and 13.1% in the standard therapy group (RR, 0.39; 95% CI, 0.14 to 1.05; P=0.05). Significantly fewer patients were rehospitalized for unstable angina in the warfarin group than in the control group (7.1% and 17.2%, respectively; RR, 0.42; 95% CI, 0.18 to 0.96; P=0.03). Two patients in the warfarin group and 1 in the control group experienced a major bleed, and there was a significant excess of minor bleeds in the warfarin group (28.6% versus 12.1%; RR, 2.36; 95% CI, 1.37 to 4.36; P=0.004). CONCLUSIONS: Long-term treatment with moderate-intensity warfarin (INR, 2.0 to 2.5) plus aspirin but not low-intensity warfarin (INR, 1.5) plus aspirin appears to reduce the rate of recurrent ischemic events in patients with AIS without ST elevation.     

Efficacy of a low molecular weight heparin administered intravenously or subcutaneously in comparison with intravenous unfractionated heparin in the treatment of deep venous thrombosis. Certoparin-Study Group

BACKGROUND: The main objective of the study presented was to test if thrombus regression can be improved by treatment with an intravenously or subcutaneously administered low molecular weight heparin (LMWH). Patients with acute deep vein thrombosis were randomly assigned to receive either intravenous UFH (131 patients), intravenous (i.v.) LMWH (128 patients), or 8000 IU of the same LMWH bid subcutaneously (s.c.) (128 patients). All patients were treated with heparin for 14 to 16 days. Vitamin-K-antagonist prophylaxis was started between Day 12 and Day 14 after enrollment into the study. METHODS: Phlebographies and perfusion/ventilation lung scans were performed at baseline and on Days 12 to 16. Primary endpoint of the study was a reduction of the phlebographic Marder score. Secondary endpoints were recurrent thrombosis and pulmonary embolism (PE), major and minor bleedings and the rate of PE at inclusion and at the end of the study assessed by ventilation/perfusion scans. RESULTS: The Marder score improved by at least 30% in 32.4% (95% CI: 22.6 ... 42.2) of the patients receiving UFH, in 34.0% (95% CI: 24.9 ... 44.0) receiving LMWH i.v. and in 42.6% (95% CI: 32.8 ... 52.8) treated with the low molecular weight heparin s.c. The difference between LMWH s.c. and UFH was 10.2% (95% CI: -3.7% ... +24.5%) (p = 0.11). PE with clinical signs confirmed by objective methods occurred in three patients of the UFH group, one of whom died and was not observed in patients of the i.v. or s.c. LMWH-groups. During the first 15 days no patient receiving UFH or i.v. LMWH, and one patient on s.c. LMWH had a recurrent thrombosis. Major bleedings were observed in four patients receiving i.v. UFH compared to nine patients on i.v. LMWH (one of these patients died) and one patient on s.c. LMWH. Perfusion ventilation lung scans were obtained from 287 patients at baseline and from 246 patients on Days 12-16. PE, defined according to PIOPED-criteria as intermediate or high probability scans, was observed in 38.0% of the patients entering the study and in 18.3% on Days 12 to 16. New asymptomatic PE occurred less frequently in the groups on LMWH (7.1%, 7.5%, respectively) than in the UFH-group (12.6%) (not significant). CONCLUSIONS: S.c. treatment with a LMWH (certoparin) (b.i.d.) is at least as effective as UFH i.v. The hypothesis of increased efficacy of subcutaneous LMWH in resolving venous thrombi will have to be confirmed by an independent study comparing s.c. LMWH with UFH. The i.v. continuous infusion of the LMWH for 12 to 16 days does not result in a higher venous re-opening rate than intravenous standard heparin.     

Hypomelanosis of Ito associated with hemimegalencephaly: a clinicopathological study

Pulmonary embolism poses a risk to patients undergoing total knee arthroplasty. The selection of an appropriate prophylaxis agent and its implementation have been influenced by decreased duration of hospital stay and the pressures of cost containment. The purpose of this study was to determine the inpatient and outpatient pulmonary embolism rates, the number of days required to attain the target level of anticoagulation, and complications associated with the use of a low-dose warfarin prophylaxis protocol after primary and revision total knee arthroplasty. Between 1984 and 1993, there were 815 primary and revision total knee arthroplasties that received low-dose warfarin prophylaxis at our institution. The average time to attainment of the target level of anticoagulation was 3 days. The average duration of warfarin prophylaxis was 12 days. Overall, there were a total of three symptomatic pulmonary embolisms (0.3%; 95% confidence interval, 0.08%-1.1%). There were eight (1%) symptomatic deep vein thromboses (all distal). There were two deaths (0.3%), but neither one was secondary to a pulmonary embolism. Seventeen knees (2.5%) developed a hematoma after surgery, and two of these patients required drainage of the knee. Low-dose warfarin prophylaxis is safe and effective in preventing symptomatic pulmonary embolism after total knee arthroplasty.     

Patient outcomes after reoperation on the lumbar spine

A prospective, randomized trial was conducted to compare the effectiveness and safety of warfarin given in two regimens in prevention of venous thrombosis after total knee replacement. Adult patients scheduled for primary or revision total knee replacement were randomly assigned to receive either a "two-step" warfarin regimen beginning 10-14 days pre-operatively or, alternatively, to begin warfarin the night before surgery. Post-operatively, the dose was adjusted in both groups to achieve a target International Normalized Ratio (INR) of 2.2 and prophylaxis was continued until venography on post-operative days five through nine. Bleeding was assessed by surgical blood loss, transfusion requirements, changes in hematocrit, and clinically identified bleeding complications. The occurrence of deep vein thrombosis was nearly the same in the two treatment groups, 39% in patients randomized to the two-step regimen as compared to 38% in those beginning the night before surgery. The occurrence of proximal vein thrombosis was also similar, 5% versus 7% (p = NS). Patients in the two-step group received 1.33 +/- 1.26 transfusions compared to 0.95 +/- 1.22 in the night before group (p < 0.05) and also had a lower nadir post-operative hematocrit of 26.7 +/- 3.1 as compared to 28.5 +/- 3.2 (p < 0.0001). Major bleeding complications were associated with excessively prolonged INRs and occurred in five patients in the two-step group and two in the night before group. Patients in both groups who developed thrombosis had a significantly lower INR on post-operative days two and three compared to those without thrombosis. We conclude that a prophylactic warfarin regimen for prevention of deep vein thrombosis after total knee replacement beginning the night before surgery is more convenient and may be associated with less bleeding than a regimen beginning warfarin 10-14 days pre-operatively. Careful control of anticoagulant intensity is needed to achieve maximum effectiveness and avoidance of bleeding complications.     

Outpatient management of deep vein thrombosis

OBJECTIVE: To assess whether patients with deep vein thrombosis (DVT) could be satisfactorily treated on an outpatient basis with low molecular weight (LMW) heparin and warfarin. DESIGN: A 22 month prospective study of adults attending St Peter's Hospital accident and emergency department with DVT. RESULTS: 1093 patients were referred and assessed; 160 were venogram positive, of which 159 patients between the ages of 22 and 89 years of age have now been treated with LMW heparin as outpatients. Direct liaison with community nurses has minimised the impact on general practitioner workload. CONCLUSIONS: 1272 bed days were saved during this period (an estimated 320,000 pounds). The outpatient treatment of thromboembolism has been shown to be effective and safe.     

Effect of warfarin on activated partial thromboplastin time in patients receiving heparin

BACKGROUND: The activated partial thromboplastin time (APTT) is used to adjust heparin sodium dosage. However, warfarin sodium is often administered concomitantly with heparin and may also affect the APTT and, therefore, heparin dose. We performed a prospective cohort study to quantify the effect of warfarin on the APTT in patients who are being treated with heparin. METHODS: Serial assays of APTT, international normalized ratio, heparin levels, and functional levels of prothrombin (factor II) and factors VII and X were performed in 24 patients with acute venous thromboembolism who were treated with concomitant continuous intravenous heparin and warfarin. The effects of warfarin, as expressed by international normalized ratio and coagulation factor levels, on APTT were determined. RESULTS: Warfarin markedly affected APTT; for each increase of 1.0 in the international normalized ratio, the APTT increased 16 seconds (95% confidence interval, 10-22 seconds). The effects of warfarin and heparin on APTT were additive. Consequently, warfarin markedly altered the relationship between APTT and heparin levels; of the 29 blood samples with supratherapeutic APTT, 13 had a therapeutic heparin level and 10 had a subtherapeutic heparin level. CONCLUSIONS: In patients receiving concomitant heparin and warfarin therapy, APTT reflects the combined effects of both drugs. Because of the marked effect of warfarin on the APTT, decreasing heparin dose in response to a high APTT frequently results in subtherapeutic heparin levels.     

Prevention of the extension of distal deep venous thrombosis. A randomized controlled trial with a 6-month follow-up

BACKGROUND: Deep venous thrombosis (DVT) of distal veins of the legs is important for its frequency and its potential proximal extension. The incidence of embolization in distal DVT is limited and treatment still undefined. METHODS: After diagnosing with duplex scanning a distal DVT patients were included in a 24-week follow-up. All subjects used elastic compression (stockings TED = thromboembolic deterrent) for 24 weeks after DVT. In the 4 groups the following prophylaxis for 8 weeks were used: A: oral anticoagulant (INR 2.5). B: subcutaneous calcium heparin 0.2 ml bid (8.00 and 20.00). C: subcutaneous calcium heparin (0.5 ml at 20.00). D was the control group (only elastic TED stockings). heparin 0.2 ml bid (5000 IU) and 0.5 ml once daily (12.500 IU) were used for individuals with weight range between 65 and 90 kg. No patient was admitted into hospitals. Initially 106 patients were included. There were 17 (9.6%) drop outs and after 8 weeks 177 patients completed the study. No pulmonary embolisation or side effects were observed. In one patient (control group) an important extension of the thrombus to the femoral and iliac veins was observed. RESULTS: The percentage of thrombus reduction was higher in the treatment groups than in controls (p < 0.05). No significant differences were found among the 3 treatment groups. At 8 weeks 88.6% of patients treated with oral anticoagulant showed improvement (stability/reduction in size of the thrombus; the percentage was 88.4% in subjects treated with subcutaneous heparin bid and 93.2% in those treated with a single dosage). In the control group thrombus increase was observed in 78.3% of patients (this difference was significant in comparison with the treatment groups; p < 0.05). At the 24-week control in 97.6% of patients in group A thrombosis was reduced/stable. This percentage was 97.7% in the ca-heparin double-dose group (B) and 100% in the single dose group (C), significantly lower than in group D (75%; p < 0.05). CONCLUSIONS: Results indicate that untreated subjects with distal DVT are at risk of thrombus extension. In this study treatments were clinically equivalent. However one single dose of subcutaneous heparin is as effective as the double dose, is better tolerated, does not require haematological monitoring and has a lower cost.     

Tunneling short-term central venous catheters to prevent catheter-related infection: a meta-analysis of randomized, controlled trials

OBJECTIVE: To evaluate the efficacy of tunneling short-term central venous catheters to prevent catheter-related infections. DATA SOURCES: MEDLINE, EMBASE, conference proceedings, citation review of relevant primary and review articles, personal files, and contact with expert informants. STUDY SELECTION: From a pool of 225 randomized, controlled trials of venous and arterial catheter management, we identified 12 relevant trials and included seven of these trials in the analysis. DATA EXTRACTION: In duplicate, independently, we abstracted data on the population, intervention, outcomes, and methodologic quality. DATA SYNTHESIS: Tunneling decreased bacterial colonization of the catheter by 39% (relative risk of 0.61; 95% confidence interval [CI] of 0.39 to 0.95) and decreased catheter-related sepsis with bacteriologic confirmation by 44% (relative risk of 0.56; 95% CI of 0.31 to 1) in comparison with standard placement. The majority of the benefit in the decreased rate of catheter-sepsis came from one trial at the internal jugular site (relative risk of 0.30, 95% CI of 0.10 to 0.89) and the reduction in risk was not significant when the data from five subclavian catheter trials were pooled (relative risk of 0.71, 95% CI of 0.36 to 1.43). Tunneling was not associated with increased risk of mechanical complications from placement or technical difficulties during placement. However, this outcome was not rigorously evaluated. CONCLUSIONS: Tunneling decreases central venous catheter-related infections. However, current evidence does not support routine tunneling until its efficacy is evaluated at different placement sites and relative to other interventions.     

Low-molecular-weight heparins

Low-molecular-weight heparins (LMWH) are a new group of parenteral anticoagulants. They represent a major clinical advance in anticoagulation since the identification of unfractionated heparin (UFH) in 1922 and the introduction of the synthetic coumarin derivative, warfarin, in 1948. Their predictable pharmacokinetics, increased bioavailability, and longer plasma half-life allow for once- or twice-daily dosing and eliminate the need for routine laboratory monitoring. This simplified administration stands to alter the clinical practice of anticoagulation. This review high-lights recent clinical trials and focuses on studies comparing LMWH with the other two major anticoagulants: UFH and coumadin.     

Aging and heparin-related bleeding

BACKGROUND: Many studies have suggested that elderly patients are at increased risk of bleeding during heparin therapy. OBJECTIVE: To establish whether the risk of bleeding in the elderly results from concomitant risk factors or is associated with the aging process itself. METHODS: One hundred ninety-nine patients who presented with proximal deep vein thrombosis were treated with a standard intravenous heparin protocol in a double-blind, randomized, prospective study. Bleeding complications were monitored. Activated partial thromboplastin times and heparin levels were assessed 4 to 6 hours after a standard intravenous heparin bolus and infusion. Heparin doses and heparin levels were also assessed after stable therapeutic heparin infusion rates were established. RESULTS: There was an increase in total and major bleeding complications with aging (P < .05) that was not accounted for by standard risk factors for bleeding. Aging was associated with an increase in heparin levels (r = .239, P = .003) and a tendency for an increase in activated partial thromboplastin time (r = .134, P = .07) after standard heparin doses. Aging was also associated with lower heparin dose requirements (r = .267, P = .003) after therapeutic activated partial thromboplastin times were achieved. CONCLUSION: Aging is a risk for heparin-related bleeding that may be explicable by age-related changes in the pharmacologic characteristics of heparin.     

Low molecular weight heparin and unfractionated heparin in thrombosis prophylaxis after major surgical intervention: update of previous meta-analyses

BACKGROUND: Previous meta-analyses comparing low molecular weight heparin (LMWH) and unfractionated heparin for thrombosis prophylaxis after surgical interventions need updating. METHODS: This is a publication-based meta-analysis of 36 double-blind studies including 16583 patients. Main outcome measures are incidence of deep vein thrombosis (efficacy) and wound haematoma (safety). RESULTS: In general surgery there is no increased efficacy in favour of LMWH (odds ratio (OR) 0.88, 95 per cent confidence interval (c.i.) 0.60-1.30) but there exists a higher incidence of bleeding complications (OR 1.47, 95 per cent c.i. 1.07-2.01). Low-dose LMWH is equally efficacious (OR 1.03, 95 per cent c.i. 0.85-1.26) but safer than unfractionated heparin (OR 0.68, 95 per cent c.i. 0.56-0.82). In orthopaedic surgery there is a trend towards an increased efficacy for LMWH (OR 0.83, 95 per cent c.i. 0.68-1.02) with equivalent safety (OR 0.96, 95 per cent c.i. 0.68-1.36). CONCLUSION: A superiority of LMWH is suggested but heterogeneity might make generalizability to future patients questionable. A meta-analysis on individual patient data should be the next step before randomizing additional patients in future trials.     

Risk factors for incident radiographic knee osteoarthritis in the elderly: the Framingham Study

OBJECTIVE: Knee osteoarthritis (OA) is highly prevalent, especially in the elderly. Preventive strategies require a knowledge of risk factors that precede disease onset. The present study was conducted to determine the longitudinal risk factors for knee OA in an elderly population. METHODS: A longitudinal study of knee OA involving members of the Framingham Study cohort was performed. Weight-bearing knee radiographs were obtained in 1983-1985 (baseline) and again in 1992-1993. Incident disease was defined as the occurrence of new radiographic OA (Kellgren and Lawrence grade > or = 2 on a 0-4 scale) in those without radiographic OA at baseline. Risk factors assessed at baseline and in the interim were tested in univariate and multivariate equations to evaluate their association with incident knee OA. RESULTS: Of 598 patients without knee OA at baseline (mean age 70.5 years, 63.7% women), 93 (15.6%) developed OA. After adjustment for multiple risk factors, women had a higher risk of OA than did men (adjusted odds ratio [OR] = 1.8, 95% confidence interval [95% CI] 1.1-3.1). Higher baseline body mass index increased the risk of OA (OR = 1.6 per 5-unit increase, 95% CI 1.2-2.2), and weight change was directly correlated with the risk of OA (OR = 1.4 per 10-lb change in weight, 95% CI 1.1-1.8). Physical activity increased the risk of OA (for those in the highest quartile, OR = 3.3, 95% CI 1.4-7.5). Smokers had a lower risk than did nonsmokers (for those who smoked an average of > or = 10 cigarettes/day, OR = 0.4, 95% CI 0.2-0.8). Factors not associated with the risk of OA included chondrocalcinosis and a history of hand OA. Weight-related factors affected the risk of OA only in women. CONCLUSION: Elderly persons at high risk of developing radiographic knee OA included obese persons, nonsmokers, and those who were physically active. The direction of weight change correlated directly with the risk of developing OA.     

Overview of randomized trials of intravenous heparin in patients with acute myocardial infarction treated with thrombolytic therapy

Intravenous heparin is routinely given after thrombolytic therapy for patients with acute myocardial infarction in the United States and in some, but by no means all, other countries. Several trials have documented improved infarct-artery patency in patients treated with heparin; however, none was large enough individually to assess the effect of heparin on clinical outcomes. We performed a systematic overview of the 6 randomized controlled trials (1,735 patients) to summarize the available data concerning the risks and benefits of intravenous heparin versus no heparin after thrombolytic therapy. Mortality before hospital discharge was 5.1% for patients allocated to intravenous heparin compared with 5.6% for controls (relative risk reduction of 9%, odds ratio 0.91, 95% confidence interval 0.59 to 1.39). Similar rates of recurrent ischemia and reinfarction were observed among those allocated to heparin therapy or control. The rates of total stroke, intracranial hemorrhage, and severe bleeding were similar in patients allocated to heparin; however, the risk of any severity of bleeding was significantly higher (22.7% vs 16.2%; odds ratio 1.55, 95% confidence interval 1.21 to 1.98). There was no significant difference in the observed effects of heparin between patients receiving tissue-type plasminogen activator and those receiving streptokinase or anisoylated plasminogen streptokinase activator complex, or between patients who did and did not receive aspirin. The findings of this overview demonstrate that insufficient clinical outcome data are available to support or to refute the routine use of intravenous heparin therapy after thrombolysis. It is not known if these findings are due to lack of statistical power, inappropriate levels of anticoagulation, or lack of benefit of intravenous heparin. Large randomized studies of heparin (and of new antithrombotic regimens) are needed to establish the role of such therapy.     

Treatment of deep venous thrombosis at home: evolution from ideas to medical practice

The diagnosis of Deep Venous Thrombosis (DVT) by duplex ultrasound is absolutely possible out of specialized centers. Low Molecular Weight Heparins (LMWH) allow to obtain a greater efficacy and safety compared to Unfractionated Heparin (UFH). The control of LMWH is very reduced. Two studies have just been published on the topic of treatment of DVT at home. The group of patients treated at home with LMWH is not presenting more complications than the group of patients initially treated at the hospital with UFH. Nevertheless, these studies concern a very selective population of patients. Our center has been proceeding to a study for 4 years (1993-1997) in comparing the treatment at home of proximal DVT by LMWH then oral anticoagulant, to the initial treatment (10 days) in hospital by also using LMWH then oral anticoagulant. The first results show that there is no difference between both groups in terms of end-points: death, extension or recurrence of the thrombus, pulmonary embolism, bleeding. Therefore, the treatment of some type of proximal DVT is possible at home. Nevertheless, it is necessary to be very cautions as the population studied so far is a selected one. Etiologies of DVT are a constant obsessive fear. DVT or pulmonary embolism represents a real general disease which is going to progress along life. The intervention of a specialized center is always necessary. It is a work in team which must get the upper hand compared to an isolated medical action.     

Overview of clinical trials of hydergine in dementia

OBJECTIVE: To assess the overall effect of Hydergine (a combination drug called ergoloid mesylates) on patients with possible dementia and to investigate potential moderators of an effect. DATA SOURCES: MEDLINE, EMBASE, and two proprietary databases were searched for reports of clinical trials. STUDY SELECTION: Included were randomized, placebo-controlled, double-blind, parallel-group trials in subjects with symptoms consistent with dementia performed with specified outcome instruments and sufficient statistical information to calculate effect sizes. Forty-seven (31%) of 151 trials reviewed met selection criteria. DATA EXTRACTION: Potential moderating variables were extracted from each trial: sample size, inpatient-outpatient status, trial duration, age, gender, medication dose, publication year, and diagnostic grouping. Outcome measures were extracted with their associated statistics. DATA SYNTHESIS: The overall combined treatment effects ("adjusted d") for three types of outcome measures were calculated. Overall, Hydergine was more effective than placebo as assessed by comprehensive ratings (d = 0.47; 95% confidence interval [CI], 0.38 to 0.56; P = .0001), clinical global ratings (d = 0.56; 95% CI, 0.44 to 0.68; P = .0001), and combined neuropsychological measures (d = 0.27; 95% CI, 0.22 to 0.32; P = .0001). Inpatient status, daily doses of 4 mg or more, and vascular dementia were generally associated with larger effects. The effect in patients with possible Alzheimer's dementia was significant only for combined neuropsychological measures in five trials (d = 0.30; 95% CI, 0.16 to 0.44; P = .0001; and with a dose-response, P = .001). CONCLUSIONS: Overall, ergoloid mesylates were more effective than placebo. However, the effect in patients with possible Alzheimer's dementia was very modest at best. The dose-response relation suggests that potentially effective doses may be higher than the currently approved. The circumstances of the efficacy of Hydergine remain inadequately defined.