BACKGROUND: Pulmonary emboli (PE), or blood clots in the lungs,can be potentially fatal. Anticoagulation is the first line therapy to prevent PE. In some instances anticoagulation fails to prevent more emboli, or cannot be given because the person has a high risk of bleeding. Inferior vena caval filters (VCFs) are metal alloy devices that mechanically trap fragmented emboli from the deep leg veins en route to the pulmonary circulation. Retrievable filters are designed to be introduced and removed percutaneously. Although their deployment seems of theoretical benefit, their clinical efficacy and adverse event profile is unclear. This is the third update of a Cochrane Review first published in 2007.
OBJECTIVES: To assess the evidence for the effectiveness and safety of vena caval filters (VCFs) in preventing pulmonary embolism (PE).
SEARCH METHODS: For this review update, the Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (last searched 10 September 2019) and the Cochrane Register of Controlled Trials (CENTRAL) (2019, Issue 8) via the Cochrane Register of Studies Online. The CIS also searched MEDLINE Ovid, EMBASE Ovid, CINAHL, and AMED (1 January 2017 to 10 September 2019) and trials registries to 10 September 2019.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) and controlled clinical trials (CCTs) that examined the efficacy of VCFs in preventing PE.
DATA COLLECTION AND ANALYSIS: For this update, studies were assessed and data extracted independently. We assessed study quality with Cochrane's 'Risk of bias' tool and used the GRADE approach to assess the overall certainty of the evidence. The outcomes of interest were PE, mortality, lower limb venous thrombosis, filter-related complications and major bleeding.
MAIN RESULTS: We identified four new studies for this update, bringing the total to six included studies involving 1388 participants. The six studies were clinically heterogeneous and we were unable to carry out meta-analysis. Only two studies were considered to be both applicable in current clinical settings and of good methodological quality. One was a randomised open-label trial studying the effect of a retrievable inferior vena caval filter plus anticoagulation versus anticoagulation alone on risk of recurrent pulmonary embolism (PE) in 399 participants over three months. There was no evidence of a difference in the rates of PE, death, lower extremity deep vein thrombosis (DVT), or bleeding at three and six months after the intervention (moderate-certainty evidence). A filter was inserted in 193 people, but could only be successfully retrieved from 153. Minor filter complications were noted at six months. The second clinically relevant study was a randomised open-label trial of 240 participants who had sustained multiple traumatic injuries, allocated to a filter or no filter, three days after injury, in conjunction with anticoagulation and intermittent pneumatic compression. Prophylactic anticoagulation was initiated in both groups when it was thought safe to do so. There was no evidence of a difference in symptomatic PE, death, or lower limb venous thrombosis rates (moderate-certainty evidence). The only major filter complication was that one person required surgical removal of the filter. We are unable to draw any conclusions from the remaining four included studies. One study showed an increased incidence of long-term lower extremity DVT at eight years. Three studies are no longer clinically applicable because they utilised permanent filters which are seldom used now, or they did not use routine prophylactic anticoagulation which is current standard practice. The fourth study compared two filter types and was terminated prematurely as one filter group had a higher rate of thrombosis compared to the other filter type.
AUTHORS' CONCLUSIONS: Two of the six identified studies were relevant for current clinical settings. One showed no evidence of a benefit of retrievable filters in acute PE for the outcomes of PE, death, DVT and bleeding during the initial three months in people who can receive anticoagulation (moderate-certainty evidence). The other study did not show any benefit for prophylactic filter insertion in people who sustained multiple traumatic injuries, with respect to symptomatic PE, mortality, or lower extremity venous thrombosis (moderate-certainty evidence). We can draw no firm conclusions regarding filter efficacy in the prevention of PE from the remaining four RCTs identified in this review. Further trials are needed to assess vena caval filter effectiveness and safety, and clinical differences between various filter types.
BACKGROUND: Low molecular weight heparins (LMWHs) have been shown to be effective and safe in preventing venous thromboembolism (VTE). They may also be effective for the initial treatment of VTE. This is the third update of the Cochrane Review first published in 1999.
OBJECTIVES: To evaluate the efficacy and safety of fixed dose subcutaneous low molecular weight heparin compared to adjusted dose unfractionated heparin (intravenous or subcutaneous) for the initial treatment of people with venous thromboembolism (acute deep venous thrombosis or pulmonary embolism).
SEARCH METHODS: For this update the Cochrane Vascular Information Specialist (CIS) searched the Cochrane Vascular Specialised Register (15 September 2016). In addition the CIS searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8) in the Cochrane Library (searched 15 September 2016) and trials' registries.
SELECTION CRITERIA: Randomised controlled trials comparing fixed dose subcutaneous LMWH with adjusted dose intravenous or subcutaneous unfractionated heparin (UFH) in people with VTE.
DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, assessed for quality and extracted data.
MAIN RESULTS: Six studies were added to this update resulting in a total of 29 included studies (n = 10,390). The quality of the studies was downgraded as there was a risk of bias in some individual studies relating to risk of attrition and reporting bias; in addition several studies did not adequately report on the randomisation methods used nor on how the treatment allocation was concealed.During the initial treatment period, the incidence of recurrent venous thromboembolic events was lower in participants treated with LMWH than in participants treated with UFH (Peto odds ratio (OR) 0.69, 95% confidence intervals (CI) 0.49 to 0.98; 6238 participants; 18 studies; P = 0.04; moderate-quality evidence). After a follow-up of three months, the period in most of the studies for which oral anticoagulant therapy was given, the incidence of recurrent VTE was lower in participants treated with LMWH than in participants with UFH (Peto OR 0.71, 95% CI 0.56 to 0.90; 6661 participants; 16 studies; P = 0.005; moderate-quality evidence). Furthermore, at the end of follow-up, LMWH was associated with a lower rate of recurrent VTE than UFH (Peto OR 0.72, 95% CI 0.59 to 0.88; 9489 participants; 22 studies; P = 0.001; moderate-quality evidence). LMWH was also associated with a reduction in thrombus size compared to UFH (Peto OR 0.71, 95% CI 0.61 to 0.82; 2909 participants; 16 studies; P < 0.00001; low-quality evidence), but there was moderate heterogeneity (I² = 56%). Major haemorrhages occurred less frequently in participants treated with LMWH than in those treated with UFH (Peto OR 0.69, 95% CI 0.50 to 0.95; 8780 participants; 25 studies; P = 0.02; moderate-quality evidence). There was no difference in overall mortality between participants treated with LMWH and those treated with UFH (Peto OR 0.84, 95% CI 0.70 to 1.01; 9663 participants; 24 studies; P = 0.07; moderate-quality evidence).
AUTHORS' CONCLUSIONS: This review presents moderate-quality evidence that fixed dose LMWH reduced the incidence of recurrent thrombotic complications and occurrence of major haemorrhage during initial treatment; and low-quality evidence that fixed dose LMWH reduced thrombus size when compared to UFH for the initial treatment of VTE. There was no difference in overall mortality between participants treated with LMWH and those treated with UFH (moderate-quality evidence). The quality of the evidence was assessed using GRADE criteria and downgraded due to concerns over risk of bias in individual trials together with a lack of reporting on the randomisation and concealment of treatment allocation methods used. The quality of the evidence for reduction of thrombus size was further downgraded because of heterogeneity between studies.
OBJECTIVES: To perform a meta-analysis of randomized controlled trials assessing the effectiveness of inferior vena cava filters in patients with deep vein thrombosis for preventing pulmonary embolism. METHOD: Relevant randomized controlled trials of inferior vena cava filters for the prevention of pulmonary embolism were identified by searching electronic databases updated in February 2016. Relative risks of recurrent pulmonary embolism, recurrent deep vein thrombosis, and mortality at three months were analyzed. RESULTS: Three published randomized controlled trials were included involving a total of 863 deep vein thrombosis patients. No significant differences were detected with inferior vena cava filters placement with regard to the incidence of recurrent pulmonary embolism or fatal pulmonary embolism. There were also no significant differences in the incidence of recurrent deep vein thrombosis or mortality with inferior vena cava filters placement at three months. CONCLUSIONS: Inferior vena cava filter in addition to anticoagulation was not associated with a reduction in the incidence of recurrent pulmonary embolism as compared with anticoagulation alone in patients with deep vein thrombosis in the short term.
BACKGROUND: Inferior vena cava filters (IVC) have been used in addition to oral anticoagulation (OC) in patients at high-risk for development of new pulmonary embolism (PE). There is few data comparing the risk-benefit from adding IVC. We sought to compare the clinical outcomes from using IVC combined to OC to OC alone. METHODS: We searched Pub Med and Cochrane trough October 2015 for RCTs that directly compared IVC + OC to OC only in patients at high-risk for new development or recurrence of PE. Primary outcome was development of new PE. Secondary outcomes included recurrence of DVT, major bleeding and death. We used Fixed or Random Effect analysis using the Cochrane Handbook of Systematic Reviews and RevMan 5.2 for statistical analysis. RESULTS: Out of 571 articles, four RCTs were included. The pooled data provided 1004 patients; 503 treated with IVC+ OC and 501 with OC. Mean follow up were 3 months. IVC + OC group presented with significant less new PE compared to OC only group (1.3% vs. 3.5%, p=0.03). There was no difference between IVC + OC compared to OC only for new DVT (7.7% vs. 7.7%), major bleeding (4.3% vs. 4.1%) and death (7.3% vs. 5.5%) respectively (Figure 1). CONCLUSIONS: Our study suggests that among patients at high-risk for venous thromboembolic events, IVC use is associated with significant less development of PE. It is yet to be determined if this benefit is sustained at long-term follow and associated with survival benefit. Therefore further randomized trials are warranted.
Inferior vena cava filter (IVCF) use continues to increase in the United States (US) despite questionable clinical benefit and increasing concerns over long-term complications. For this review we comprehensively examine the randomized, prospective data on IVC filter efficacy, compare relative rates of IVCF placement in the US and Europe, compare commonly considered guidelines for IVCF indications, and the current data on IVCF complications. Searches of MEDLINE and Cochrane databases were conducted for randomized prospective IVCF studies. Only three randomized prospective studies for IVCFs were identified. Commonly cited IVCF guidelines were reviewed with attention to their evolution over time. No evidence has shown a survival benefit with IVCF use. Despite this, continued rising utilization, especially for primary prophylactic indications, is concerning, given increasing evidence of long-term filter-related complications. This is particularly noted in the US where IVCF placements for 2012 are projected to be 25 times that of an equivalent population in Europe (224,700 versus 9,070). Pending much-needed randomized controlled trials that also evaluate long-term safety, we support the more stringent American College of Chest Physicians (ACCP) guidelines for IVCF placement indications and advocate a close, structured follow-up of retrievable IVCFs to improve filter retrieval rates.
BACKGROUND: Low Molecular Weight Heparins (LMWH) are at least as effective antithrombotic drugs as Unfractionated Heparin (UFH). However, it is still unclear whether the safety profiles of LMWH and UFH differ. We performed a systematic review to compare the bleeding risk of fixed dose subcutaneous LMWH and adjusted dose UFH for treatment of venous thromboembolism (VTE) or acute coronary syndromes (ACS). Major bleeding was the primary end point.
METHODS: Electronic databases (MEDLINE, EMBASE, and the Cochrane Library) were searched up to May 2010 with no language restrictions. Randomized controlled trials in which subcutaneous LMWH were compared to intravenous UFH for the treatment of acute thrombotic events were selected. Two reviewers independently screened studies and extracted data on study design, study quality, incidence of major bleeding, patients' characteristics, type, dose and number of daily administrations of LMWH, co-treatments, study end points and efficacy outcome. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using the random effects model.
RESULTS: Twenty-seven studies were included. A total of 14,002 patients received UFH and 14,635 patients LMWH. Overall, no difference in major bleeding was observed between LMWH patients and UFH (OR = 0.79, 95% CI 0.60-1.04). In patients with VTE LMWH appeared safer than UFH, (OR = 0.68, 95% CI 0.47-1.00).
CONCLUSION: The results of our systematic review suggest that the use of LMWH in the treatment of VTE might be associated with a reduction in major bleeding compared with UFH. The choice of which heparin to use to minimize bleeding risk must be based on the single patient, taking into account the bleeding profile of different heparins in different settings.
The use of inferior vena cava (IVC) filters to prevent pulmonary embolism (PE) in patients who have or are at risk of developing deep vein thrombosis is increasing. A systematic review was performed to assess the frequency of symptoms and signs of postthrombotic syndrome (PTS) in relation to IVC filter placement. It was also assessed whether the initial indication for IVC filter placement-prevention of PE in a patient without known venous thrombosis (i.e., primary prevention) versus prevention of PE in patients with known venous thrombosis (i.e., secondary prevention)-or concurrent use of anticoagulation or compression stockings influenced this rate. Eleven articles describing 1,552 patients met criteria for review. At a mean follow-up of 4.5 years, the weighted pooled incidence of edema was 42.9% (95% CI, 40.4%-45.4%), and that of chronic skin changes (including venous ulcers) was 12.0% (95% CI, 10.3%-13.7%). Among patients who had IVC filter insertion for secondary prevention, 51.2% (95% CI, 48.3%, 54.1%) had edema and 13.5% (95% CI, 11.5%, 15.5%) had skin changes at follow-up, compared with 20.2% (95% CI, 15.7%, 24.7%) and 8.3% (95% CI, 5.2%-11.4%), respectively, in patients who received an IVC filter for primary prevention. One study reported no difference in the frequency of symptoms and signs of PTS according to whether anticoagulation was initiated in addition to filter placement. No study reported rates of PTS according to use of elastic compression stockings after filter placement. The present results raise the possibility that IVC filters could be associated with the development of PTS, including venous ulcers, when used for the primary or secondary prevention of PE. However, as a result of the important limitations of the articles reviewed, further research is required to directly address this issue.
OBJECTIVE: To review the evidence for using inferior vena cava (IVC) filters to prevent pulmonary embolism (PE) in high-risk patients. QUALITY OF EVIDENCE: Ovid MEDLINE was searched from 1966 to 2006 for all English-language papers on IVC filters. Evidence was graded according to the 3-level classification system. Most evidence found was level II. MAIN MESSAGE: Inferior vena cava filters are used to prevent PE in patients with contraindications to, complications of, or failure of anticoagulation therapy and patients with extensive free-floating thrombi or residual thrombi following massive PE. Current evidence indicates that IVC filters are largely effective; breakthrough PE occurs in only 0% to 6.2% of cases. Contraindications to implantation of IVC filters include lack of venous access, caval occlusion, uncorrectable coagulopathy, and sepsis. Complications include misplacement or embolization of the filter, vascular injury or thrombosis, pneumothorax, and air emboli. Recurrent PE, IVC thrombosis, filter migration, filter fracture, or penetration of the caval wall sometimes occur with long-term use. CONCLUSION: When used appropriately, IVC filters are a safe and effective method of preventing PE. Using retrievable filters might reduce long-term complications.
OBJECTIVE: To evaluate the effectiveness of interventional strategies for the common complications of heterotopic ossification (HO) and venous thromboembolism (VTE) following acquired brain injury (ABI). Methods and main outcomes: A systematic review of the literature from 1980-2005 was conducted focusing on interventions for HO and VTE in the ABI population. Nineteen studies examining a variety of treatment approaches were evaluated. RESULTS: The majority of interventions are supported by limited evidence, defined as an absence of randomized controlled trials (RCTs). All of the treatment approaches for HO are supported with limited evidence. For VTE, there is moderate evidence, defined as at least one positive RCT, indicating that low-molecular-weight heparin is more effective than low-dose unfractionated heparin in preventing VTE, low-molecular-weight heparin is as effective and safe as unfractionated heparin for the prevention of pulmonary thromboembolism, low-molecular-weight heparin combined with compression stockings is more effective than compression stockings alone for the prevention of VTE and intermittent pneumatic compression devices are as effective as low-molecular-weight heparin for the prevention of VTE. CONCLUSIONS: There are a variety of intervention and prophylactic strategies that have been postulated to treat and reduce the incidence of these complications, with the goal of improving rehabilitation outcomes. It is therefore important to investigate the efficacy of these treatment strategies to provide guidance for clinical practice based on the best available evidence. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
STUDY OBJECTIVES: Low-molecular-weight heparins have been compared with unfractionated heparin (UFH) for treatment of deep vein thrombosis (DVT). However, a comparison of their efficacy in the presence or absence of pulmonary embolism (PE) has not been studied. We estimated the efficacy and safety of enoxaparin vs UFH in patients with proximal DVT with/without symptomatic PE using a meta-analysis of individual data from randomized controlled trials. DESIGN AND SETTING: Randomized controlled trials were identified from MEDLINE, EMBASE, abstracts from international meetings on venous thromboembolism (VTE), previous meta-analyses, and trial data provided by the sponsor. PARTICIPANTS: For inclusion, randomized controlled trials had to be properly randomized; include patients with objectively diagnosed DVT; compare enoxaparin twice daily with UFH; use objective methods to assess recurrent symptomatic VTE, major bleeding, and death at 3 months; and include blind evaluation of clinical events. MEASUREMENTS: A meta-analysis was performed using the logarithm of the relative risk (RR) method. Enoxaparin in DVT treatment with/without symptomatic PE was considered noninferior to UFH for preventing VTE at 3 months if the upper limit of the 95% confidence interval (CI) of the RR (enoxaparin/UFH) was lower than a prespecified noninferiority margin (1.61). No increase in major bleeding or mortality should be observed. RESULTS: The meta-analysis included individual data from three randomized controlled trials (749 patients and 754 patients in the enoxaparin and UFH groups, respectively). The observed RR (enoxaparin/UFH) of VTE was 0.81 (95% CI, 0.52 to 1.26) for the intention-to-treat population (RR, 0.70; 95% CI, 0.43 to 1.13; for per-protocol analysis). Results did not differ for patients with clinical PE (235 patients; RR, 0.84) and without clinical PE (1,268 patients; RR, 0.71), with a nonsignificant heterogeneity test between groups (p = 0.76). A trend in favor of enoxaparin was observed for reduced mortality and major bleeding. CONCLUSIONS: The efficacy and safety of enoxaparin vs UFH for DVT treatment is not modified by the presence of symptomatic PE.
Pulmonary emboli (PE), or blood clots in the lungs,can be potentially fatal. Anticoagulation is the first line therapy to prevent PE. In some instances anticoagulation fails to prevent more emboli, or cannot be given because the person has a high risk of bleeding. Inferior vena caval filters (VCFs) are metal alloy devices that mechanically trap fragmented emboli from the deep leg veins en route to the pulmonary circulation. Retrievable filters are designed to be introduced and removed percutaneously. Although their deployment seems of theoretical benefit, their clinical efficacy and adverse event profile is unclear. This is the third update of a Cochrane Review first published in 2007.
OBJECTIVES:
To assess the evidence for the effectiveness and safety of vena caval filters (VCFs) in preventing pulmonary embolism (PE).
SEARCH METHODS:
For this review update, the Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (last searched 10 September 2019) and the Cochrane Register of Controlled Trials (CENTRAL) (2019, Issue 8) via the Cochrane Register of Studies Online. The CIS also searched MEDLINE Ovid, EMBASE Ovid, CINAHL, and AMED (1 January 2017 to 10 September 2019) and trials registries to 10 September 2019.
SELECTION CRITERIA:
We included randomised controlled trials (RCTs) and controlled clinical trials (CCTs) that examined the efficacy of VCFs in preventing PE.
DATA COLLECTION AND ANALYSIS:
For this update, studies were assessed and data extracted independently. We assessed study quality with Cochrane's 'Risk of bias' tool and used the GRADE approach to assess the overall certainty of the evidence. The outcomes of interest were PE, mortality, lower limb venous thrombosis, filter-related complications and major bleeding.
MAIN RESULTS:
We identified four new studies for this update, bringing the total to six included studies involving 1388 participants. The six studies were clinically heterogeneous and we were unable to carry out meta-analysis. Only two studies were considered to be both applicable in current clinical settings and of good methodological quality. One was a randomised open-label trial studying the effect of a retrievable inferior vena caval filter plus anticoagulation versus anticoagulation alone on risk of recurrent pulmonary embolism (PE) in 399 participants over three months. There was no evidence of a difference in the rates of PE, death, lower extremity deep vein thrombosis (DVT), or bleeding at three and six months after the intervention (moderate-certainty evidence). A filter was inserted in 193 people, but could only be successfully retrieved from 153. Minor filter complications were noted at six months. The second clinically relevant study was a randomised open-label trial of 240 participants who had sustained multiple traumatic injuries, allocated to a filter or no filter, three days after injury, in conjunction with anticoagulation and intermittent pneumatic compression. Prophylactic anticoagulation was initiated in both groups when it was thought safe to do so. There was no evidence of a difference in symptomatic PE, death, or lower limb venous thrombosis rates (moderate-certainty evidence). The only major filter complication was that one person required surgical removal of the filter. We are unable to draw any conclusions from the remaining four included studies. One study showed an increased incidence of long-term lower extremity DVT at eight years. Three studies are no longer clinically applicable because they utilised permanent filters which are seldom used now, or they did not use routine prophylactic anticoagulation which is current standard practice. The fourth study compared two filter types and was terminated prematurely as one filter group had a higher rate of thrombosis compared to the other filter type.
AUTHORS' CONCLUSIONS:
Two of the six identified studies were relevant for current clinical settings. One showed no evidence of a benefit of retrievable filters in acute PE for the outcomes of PE, death, DVT and bleeding during the initial three months in people who can receive anticoagulation (moderate-certainty evidence). The other study did not show any benefit for prophylactic filter insertion in people who sustained multiple traumatic injuries, with respect to symptomatic PE, mortality, or lower extremity venous thrombosis (moderate-certainty evidence). We can draw no firm conclusions regarding filter efficacy in the prevention of PE from the remaining four RCTs identified in this review. Further trials are needed to assess vena caval filter effectiveness and safety, and clinical differences between various filter types.
