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Take a look at a selection of our recent media coverage:
5th December 2022
Taking rivaroxaban for 12 weeks rather than 6, following an isolated deep vein thrombosis, significantly reduces the risk of a recurrent thromboembolic event over the next two years according to the results of a randomised, double-blind, placebo-controlled trial by Italian researchers.
An isolated distal deep vein thrombosis (DVT) accounts for between a quarter and a half of all leg DVTs. Moreover, left untreated, an isolated distal DVT can extend to the proximal veins or cause a pulmonary embolism in between 1% and 22% of cases. Treatment of an isolated DVT involves the use of anticoagulants both therapeutically and prophylactically although the duration of the therapy to prevent recurrent events is uncertain. In a meta-analysis of studies, it was clearly shown that anticoagulant therapy reduced the risk of venous thromboembolism in patients. However, the review also found that there was a lower rate of recurrent venous thromboembolism in patients who received longer than 6 weeks of anticoagulant therapy.
With a suggestion that longer duration anticoagulation appeared to reduce the risk of a recurrent thromboembolic event, in the present study, researchers compared the impact on recurrent events of either a 6- or 12-week course of rivaroxaban. They recruited patients diagnosed with a symptomatic isolated distal DVT of the leg and who were then given rivaroxaban 15 mg twice daily for three weeks and then 20 mg daily for a further three weeks. At this point, participants who had not developed any thrombotic and haemorrhagic events, were randomised 1:1 to either continue with rivaroxaban 20 mg daily or matching placebo for a further 6 weeks. The primary efficacy outcome was a recurrent venous thromboembolism during the follow-up and the primary safety outcome was major bleeding, after randomisation.
Rivaroxaban and recurrent thromboembolism
A total of 402 individuals with a mean age of 65 years (58% women) were included and randomised to rivaroxaban (200) or placebo and followed for 24 months.
A recurrent thromboembolism occurred in 11% of rivaroxaban patients and 19% of those assigned to placebo (relative risk, RR = 0.59, 95% CI 0.36 – 0.95, p = 0.03). A recurrent isolated distal DVT recurred significantly less frequently, occurring in 8% and 15% of the rivaroxaban and placebo groups respectively (p = 0.02). However, a proximal or pulmonary embolism occurred in an equally small number of patients in each group and there were no major bleeding events.
The authors concluded that giving rivaroxaban for 3 months in patients with and isolated distal DVT who did not experience any events during the first 6 weeks of therapy reduced the risk of recurrent venous thromboembolism.
12th July 2022
A network meta-analysis by a collaborate team from the Netherlands, Denmark and the UK has suggested that intermediate dose low molecular weight (LMW) heparins offer the greatest balance of benefit and harm for the prevention of venous thromboembolism (VTE) in acute ill hospitalised patients.
Venous thromboembolism is not uncommon with one US study estimating that a VTE occurs in approximately 100 persons per 100,000 each year and that an estimated one third of these patients will also develop a pulmonary embolism. Furthermore, VTEs are commonly seen in those with limited movement as revealed in another study that observed how 59% of VTWs in the community could be attributed to institutionalisation such as current or recent hospitalisation or nursing home residence.
Although any of the available anticoagulants such as intermediate dose LMW heparins, unfractionated heparin or even oral anticoagulants are effective for the prevention of a VTE, there are differences in the risk-benefit profile of each of the different agents leading to differences in guidance produced by national bodies.
For example, in the UK, NICE advocates the use of LMW heparins as a first-line treatment for the prevention of venous thromboembolism in acutely ill patients. In contrast, the American Society for Haematology suggests that for acutely ill medical patients, clinicians can use unfractionated heparin, LMW heparins or fondaparinux.
These slight differences have no doubt arise because to date, there is a lack of comparative data on the most appropriate anticoagulant type and dose for the management of VTE in acutely ill patients.
For the present study, researchers performed a systematic review and network meta-analysis to assess the benefits and harms of different types and doses of anticoagulant drugs for prevention of venous thromboembolism in acutely ill adults who have been admitted to hospital.
To assess the effectiveness of different anticoagulants, they used a composite primary outcome of all-cause mortality, symptomatic venous thromboembolism, major bleeding and serious adverse events.
Intermediate dose LMW heparins and outcomes
A total of 44 randomised trials with 90,095 participants and a median age of 68.5 years (46.5% women) were included in the analysis.
Thirty-six trials reported on all-cause mortality but interestingly, none of the interventions reduced all-cause mortality in comparison to placebo. However, when compared to no intervention, intermediate dose low-molecular-weight heparins led to a significant reduction (odds ratio, OR = 0.79, 95% CI 0.61 to 0.96) as did pentasaccharides (OR = 0.44, 95% CI 0.20 to 0.92).
Intermediate dose LMW heparins were the only intervention to reduce the incidence of symptomatic venous thromboembolism compared to placebo (OR = 0.66, 95% CI 0.46 – 0.93) but all of the interventions were effective compared to no treatment.
Both intermediate dose unfractionated heparin and direct oral anticoagulants were the two groups of agents most likely to increase major bleeding though there were no apparent differences between the different interventions with respect to the incidence of major adverse effects.
Based on these findings, the authors concluded that intermediate dose LMW heparins conferred the best balance of benefits and harms for prevention of venous thromboembolism in acutely ill hospitalised patients. In contrast, unfractionated heparin, in particular the intermediate dose and direct oral anticoagulants had the least favourable profile.
17th March 2022
Direct acting oral anticoagulants (DOACs) are more effective for the prevention of symptomatic venous thromboembolism in comparison to prophylactic dosing with low molecular weight (LMW) heparins.
However, DOCAs are no more effective than high dose LMW heparins in non-cardiac surgical patients. This was the conclusion of a systemic review and network meta-analysis by researchers from the Department of Health Research Methods, Evidence, and Impact, McMaster University, Ontario, Canada
A venous thromboembolism is a significant problem in the peri-operative period with the potential to increase patient morbidity, mortality and associated health care costs. Typically, a venous thromboembolism presents as either a deep vein thrombosis or a pulmonary embolism.
Although both the DOACs and LMW heparins are recognised as convenient and effective prophylaxis regimens against venous thromboembolism for at-risk surgical patients, there is a lack of direct and comparative evidence to guide clinician’s choice. Nevertheless, it seems that in practice, one survey of thrombosis experts revealed how 85.9% would recommend the use of LMW heparins.
With a level of uncertainty over the relative benefits of either DOACs or LMW heparins, the Canadian team undertook a systematic review and network meta-analysis of existing randomised controlled trials in which there was a comparison of LMW heparins, DOACs and no active treatment for thromboprophylaxis in patients undergoing non-cardiac surgery.
The researchers suspected that the relative efficacy of the two therapeutic options would be similar across a range of surgical settings and hence used a network meta-analysis to enable a comparison to be made where there was an absence of direct comparative studies.
The team included randomised trials in adult patients (> 18 years of age) undergoing non-cardiac surgery, including general, urological, gynaecological, orthopaedic and thoracic procedures. They searched for studies in which the use of low dose LMW heparins (e.g., enoxaparin 40 mg daily), high dose (e.g., enoxaparin 30 mg twice daily) and DOACs had been employed.
The outcome of interest was a reduction in symptomatic pulmonary embolism and/or deep vein thrombosis and they considered major bleeding as the primary anticipated harm.
DOACs and symptomatic venous thromboembolism
A total of 68 eligible studies with 45,445 patients were included in the analysis. In 25 trials with 30, 230 patients, 0.78% had a symptomatic venous thromboembolism and in 61 studies, 0.25% had a pulmonary embolism.
Overall and compared to no treatment, all three interventions were associated with a significant reduction in the odds of symptomatic venous thromboembolism. For example, DOACs (OR = 0.17, 95% CI 0.07 – 0.41), LMW heparins (OR = 0.33) and high dose LMW heparins (OR = 0.19).
When the different treatments were compared in the network meta-analysis, the use of DOACs was associated with a significant reduction in symptomatic venous thromboembolism compared to LMW heparin (odds ratio, OR = 0.53, 95% CI 0.32 – 0.89, p = 0.02). However, there was no significant difference compared to high dose LMH heparin (OR = 0.93, 95% CI 0.51 – 1.71).
In terms of bleeding, both DOACs and both doses of LMW heparins were associated with an increased risk of a major bleed. The risk was approximately two-fold higher for both DOACs and LMW heparins (e.g., OR = 2.01 for DOACs).
The authors concluded that both DOACs and LMW heparins are effective for symptomatic venous thromboembolism in non-cardiac surgery and that the former class of drugs are probably more effective and LMW heparins when used at the standard prophylactic dose.
Marcucci M et al. Benefits and harms of direct oral anticoagulation and low molecular weight heparin for thromboprophylaxis in patients undergoing non-cardiac surgery: systematic review and network meta-analysis of randomised trials BMJ 2022
27th January 2022
Prolonged TV viewing is associated with an increased risk of venous thromboembolism even among those who are physically active. This was the conclusion of a meta-analysis by a team from the National Institute for Health Research Bristol Biomedical Research Centre, Bristol, UK.
Both arterial thrombosis and venous thromboembolism (VTE) have been generally perceived as two distinct entities and while the traditional risk factors for arterial disease are not strongly associated with an increased risk of VTE, patients with VTE do carry these risk factors.
Physical inactivity or sedentary behaviour, has been found to be independently associated with adverse cardiovascular outcomes, regardless of physical activity levels, whereas in contrast, a 2020 meta-analysis of 14 prospective studies, concluded that physical activity was protective such that higher levels of regular physical activity resulted in a lower incidence of VTE.
Prolonged TV viewing is a sedentary behaviour and thus intuitively linked to an increased risk of VTE. However, the available evidence is conflicting, with one study finding that greater frequency of TV viewing was independently associated with increased risk of VTE whereas another study found no evidence of an interaction between TV viewing, physical activity and the risk of VTE.
In trying to provide further clarity, the UK team sought to evaluate the magnitude of the prospective association between prolonged TV viewing and the risk of VTE. To enhance comparison and interpretations of the findings, the team dichotomised the data as prolonged vs never/seldom TV viewing.
From a total of 28 potentially eligible studies, only 3, which represented unique prospective cohort studies, including 131, 421 individuals and 964 VTE events with a follow-up duration of 5.1 to 19.8 years, were usable for their analysis.
The pooled multivariable adjusted relative risk (RR) of VTE comparing prolonged TV viewing compared to seldom/never, was 1.35 (95% CI 1.07 – 1.70). Interestingly, this positive association remained even after adjustment for physical activity which suggests that even though an individual might achieve the recommended amount of physically activity, this does not fully eliminate the risk of a VTE.
Based on these findings, the authors concluded that the results supported an association between prolonged TV viewing and a greater risk of a VTE. They added that frequent breaks and maintaining recommended levels of physical activity might be needed for VTE prevention but that further studies are required to explore this association in more detail.
Kunutsor SK et al. Television viewing and venous thrombo-embolism: a systematic review and meta-analysis Eur J Prev Cardiol 2022.