1.5.49.

Consider pharmacological VTE prophylaxis with LMWH^kk for a minimum of 7 days for people who are undergoing open vascular surgery or major endovascular procedures, including endovascular aneurysm repair whose risk of VTE outweighs their risk of bleeding. [2018]

1.5.50.

Consider mechanical VTE prophylaxis on admission for people who are undergoing open vascular surgery or major endovascular procedures, including endovascular aneurysm repair, if pharmacological prophylaxis is contraindicated. Choose either:

• anti-embolism stockings or
• intermittent pneumatic compression.

Continue until the person no longer has significantly reduced mobility relative to their normal or anticipated mobility. [2018]

The committee considered all-cause mortality (up to 90 days from hospital discharge), deep vein thrombosis (symptomatic and asymptomatic) (up to 90 days from hospital discharge), pulmonary embolism (symptomatic and asymptomatic) (up to 90 days from hospital discharge), fatal PE (up to 90 days from hospital discharge), and major bleeding (up to 45 days from hospital discharge) as critical outcomes.

The committee considered clinically relevant non-major bleeding (up to 45 days from hospital discharge), health-related quality of life (up to 90 days from hospital discharge), heparin-induced thrombocytopaenia (duration of study), and technical complications of mechanical interventions (duration of study) as important outcomes.

Please see section 4.4.3 in the methods chapter for further detail on prioritisation of the critical outcomes.

Three studies were included in this section, which were of different populations including people undergoing vascular surgery including aortic or aortoiliac aneurysm repair, aorto-femoral bypass for atherosclerotic disease, and femoropopliteal or femorodistal bypass; people undergoing elective aortic bifurcation graft surgery; and people undergoing aortic reconstruction, carotid artery surgery, lumbar sympathectomy, leg revascularisation, psuedoaneurysm repair and repair of artiovenous fistulae.

All of the evidence was of very low quality for both UFH compared to no prophylaxis, and for LMWH compared to UFH. This was due to risk of bias, indirectness and imprecision. The outcomes for both studies were downgraded for indirectness as the definition of the outcome of the study or the timepoint at which the outcome was measured did not match the protocol or was not reported. For DVT, both studies specified this was confirmed by fibrinogen scanning, which the committee did not consider to be an accurate measure of confirmation.

Many people having major arterial surgery are older and potentially immobile, putting them at risk for VTE. However many will already be receiving anticoagulation or antiplatelet therapy and therefore be at greater risk of bleeding or admitted with bleeding as emergencies. In addition, full dose heparin is frequently administered during surgery for arterial disease prior to arterial clamping. Major aortic procedures are done either by open techniques or more minimally invasive endovascular techniques but both tend to be long procedures often lasting several hours and both are associated with a significant risk of VTE. Post-operatively return to full mobility can be significantly delayed after vascular surgery especially for open procedures. The committee noted that there was little RCT evidence in the open vascular surgery population but given their likelihood of extended immobility they considered it would be appropriate for clinicians to consider pharmacological prophylaxis with LMWH for those at low risk of bleeding. For those people whose risk of bleeding outweighs their risk of VTE, the committee agreed mechanical prophylaxis could be considered. Given the lack of evidence identified for different forms of mechanical prophylaxis the committee considered it would best to offer clinicians the choice between AES and IPC. Most people who are vascular patients will have peripheral arterial disease; this means they are not usually able to use AES. Intermittent compression can be used but may impair postoperative mobilisation and rehabilitation.

Mechanical prophylaxis is recommended until the patient is back to normal mobility as the committee consider that mechanical prophylaxis offers little benefit once a patient is mobile. Pharmacological prophylaxis is recommended for a minimum of 7 days because the average duration of trials extrapolated from the abdominal surgery was between 7 and 10 days.

No economic studies were identified for this review. The unit costs were presented to the committee. The committee considered the clinical evidence presented for each stratum alongside the unit costs presented.

Based on the doses reported in the included clinical studies, the cost of using UFH (Heparin sodium) ranged from £9 to £59. Using the BNF recommended dose the cost was £24.6 (assuming administration for 7 days). For LMWH (enoxaparin sodium) the cost ranged from £24 to £91 (based on the included studies’ doses). Using the BNF recommended dose the cost was £24.2 (assuming administration for 7 days). The cost of nurse time required for administration was higher for UFH compared to LMWH due to the higher frequency of administration. UFH also required more monitoring tests (full blood count).

Hence, LMWH was recommended as the preferred pharmacological prophylaxis modality as it was considered to be more cost effective, given the reduced frequency of administration and need for monitoring.

For those with contraindications to pharmacological prophylaxis, it was noted that AES are unlikely to be suitable due to the likelihood having peripheral arterial disease. In the absence of other suitable mechanical options the committee considered that IPC would be the only potential option and is likely to be cost effective in this population given their high VTE risk.

1.5.51.

Consider pharmacological VTE prophylaxis with LMWH^ll for a minimum of 7 days for people who are undergoing lower limb amputation whose risk of VTE outweighs their risk of bleeding. [2018]

1.5.52.

Consider mechanical VTE prophylaxis with intermittent pneumatic compression on the contralateral leg, on admission, for people who are undergoing lower limb amputation and if pharmacological prophylaxis is contraindicated. [2018]

1.5.53.

For people undergoing lower limb amputation, continue mechanical VTE prophylaxis until the person no longer has significantly reduced mobility relative to their anticipated mobility. [2018]

The committee considered all-cause mortality (up to 90 days from hospital discharge), deep vein thrombosis (symptomatic and asymptomatic) (up to 90 days from hospital discharge), pulmonary embolism (symptomatic and asymptomatic) (up to 90 days from hospital discharge), fatal PE (up to 90 days from hospital discharge), and major bleeding (up to 45 days from hospital discharge) as critical outcomes.

The committee considered clinically relevant non-major bleeding (up to 45 days from hospital discharge), health-related quality of life (up to 90 days from hospital discharge), heparin-induced thrombocytopaenia (duration of study), and technical complications of mechanical interventions (duration of study) as important outcomes.

Please see section 4.4.3 in the methods chapter for further detail on prioritisation of the critical outcomes.

There was a lack of direct evidence for the amputation population but those undergoing lower limb amputation are known to have a very high risk of VTE in the amputated leg due to surgical trauma and ligation of the vein, and they will be relatively immobile both before and after the surgery which also puts them at higher risk of VTE in the non-amputated leg. Most people who are vascular patients having amputation will have peripheral arterial disease; this means they are not usually able to use AES on the contralateral limb and not at all on the side of the amputation. Likewise, intermittent pneumatic compression can only be used on the contralateral limb. In view of their high risk and the unsuitability of mechanical methods, extrapolation from evidence in other high risk groups means it is likely that these patients will need pharmacological prophylaxis. If there is the occasional person who has a high bleeding risk such that pharmacological prophylaxis cannot be used, then due to their high risk of VTE they should receive mechanical prophylaxis on the contralateral leg.

Mechanical prophylaxis is recommended until the patient is back to normal mobility as the committee consider that mechanical prophylaxis offers little benefit once a patient is mobile. Pharmacological prophylaxis is recommended for a minimum of 7 days because the average duration of trials extrapolated from the abdominal surgery was between 7 and 10 days.

No economic studies were identified for this review. The unit costs were presented to the committee. The committee considered the clinical evidence presented for each stratum alongside the unit costs presented.

The clinical evidence showed that there was no clinical difference for LMWH compared to UFH with regard to DVT and major bleeding. Given the lower cost of LMWH compared to UFH it was considered to be the cost effective option, being equally effective and less costly.

1.5.54.

Be aware that VTE prophylaxis is generally not needed for people undergoing varicose vein surgery where:

• total anaesthesia time is less than 90 minutes and
• the person is at low risk of VTE. [2018]

1.5.55.

Consider pharmacological VTE prophylaxis with LMWH^mm, starting 6–12 hours after surgery and continuing for 7 days for people undergoing varicose vein surgery if:

• total anaesthesia time is more than 90 minutes or
• the person’s risk of VTE outweighs their risk of bleeding. [2018]

1.5.56.

Consider mechanical VTE prophylaxis with anti-embolism stockings, on admission, for people undergoing varicose vein surgery:

• who are at increased risk of VTE and
• when pharmacological prophylaxis is contraindicated. [2018]

1.5.57.

If using anti-embolism stockings for people undergoing varicose vein surgery, continue until the person no longer has significantly reduced mobility relative to their normal or anticipated mobility. [2018]

The committee considered all-cause mortality (up to 90 days from hospital discharge), deep vein thrombosis (symptomatic and asymptomatic) (up to 90 days from hospital discharge), pulmonary embolism (symptomatic and asymptomatic) (up to 90 days from hospital discharge), fatal PE (up to 90 days from hospital discharge), and major bleeding (up to 45 days from hospital discharge) as critical outcomes.

The committee considered clinically relevant non-major bleeding (up to 45 days from hospital discharge), health-related quality of life (up to 90 days from hospital discharge), heparin-induced thrombocytopaenia (duration of study), and technical complications of mechanical interventions (duration of study) as important outcomes.

Please see section 4.4.3 in the methods chapter for further detail on prioritisation of the critical outcomes.

Four studies were included that looked at prophylaxis in people undergoing varicose vein surgery.

One study (San Noberto 2013) focused on comparing mechanical prophylaxis (IPCD then AES) with and without LMWH. All of the evidence was of very low quality due to risk of bias and imprecision.

Another study (Wang 2015) compared both LMWH, UFH and no prophylaxis. Some evidence was of high quality; however the majority of evidence was of very low quality. The evidence for both LMWH versus no prophylaxis, and for UFH versus no prophylaxis with regards to DVT and PE, was of high quality, however the evidence for major bleeding was of low quality due to indirectness of the outcome definition. The evidence for LMWH compared to UFH with regards to DVT, PE and major bleeding was all of low quality due to imprecision. The committee noted that Wang 2015 used open vein surgery for varicose veins, which is not a type of surgery recommended by NICE for this condition.

Two further studies (Ayo 2017 and Ye 2016) compared anti-embolism stockings with no compression which were assessed as high risk of bias due to selection concerns and high rates of missing data. Some of the evidence was also downgraded due to intervention indirectness as patients were included in the study twice if they required bilateral treatment. Evidence was further downgraded due to imprecision around the effect estimates for the quality of life outcomes.

Varicose vein surgery is a relatively common procedure as varicose veins affect a large proportion of the population. The majority of people undergoing surgery for varicose veins are women; therefore oral contraceptive use and hormone replacement therapy use are common in this surgical population. Open varicose vein surgery is now becoming less common and more surgery is being performed using minimally invasive catheter techniques, often under local anaesthetic. People undergoing varicose vein surgery are considered to be at risk for VTE, and DVT and PE are the most common serious complications related to varicose vein surgery. The committee considered that the risk is high enough that pharmacological prophylaxis should be considered for at risk persons undergoing varicose vein surgery. Anti-embolism stockings were considered to be the preferred mechanical prophylaxis strategy in this population as they are usually mobile and not suitable for IPC.

Mechanical prophylaxis is recommended until the patient is back to normal mobility as the committee believe that mechanical prophylaxis offers little benefit once a patient is mobile. Pharmacological prophylaxis is recommended for a minimum of 7 days because the average duration of trials extrapolated from the abdominal surgery was between 7 and 10 days.

No economic studies were identified for this review. The unit costs were presented to the committee. The committee considered the clinical evidence presented for each stratum alongside the unit costs presented.

The clinical evidence showed a possible benefit of LMWH for DVT and major bleeding but no difference for PE when compared with UFH. Given the lower cost of LMWH, it was considered to be the dominant pharmacological prophylaxis option in this population (more effective and less costly).