Intermittent pneumatic compression for preventing deep vein thrombosis in acute stroke, a health technology assessment
Health technology assessment|
Vi har på oppdrag fra Bestillerforum RHF i Nye metoder oppsummert effekt og sikkerhet samt utført en helseøkonomisk vurdering av intermitterende pneumatisk kompresjon (IPC) sammenliknet med ingen bruk for å forebygge dyp venetrombose hos immobile pasienter med akutt hjerneslag.
We summarized the efficacy and safety of using intermittent pneumatic compression (IPC) compared with no IPC to prevent deep vein thrombosis in immobile patients with acute stroke. In addition, we conducted a health economic assessment. This report was commissioned by Bestillerforum RHF in Nye metoder. We included one big, CLOTS 3, and two small randomised controlled trials. The outcomes were measured after 30 days and after 6 months. We assessed the confidence in the effect estimates with the GRADE tool (high, moderate, low and very low confidence).
We found that IPC compared with no IPC in immobile patients with acute stroke:
- probably reduces the risk of both distal and proximal venous thrombosis (GRADE: moderate)
- reduces the risk of proximal thrombosis to the same extent in cerebral haemorrhage as in ischemic stroke measured after 30 days
- may make little or no difference in risk of pulmonary embolism compared to no IPC (GRADE: low)
- may lead to a small reduction in mortality (GRADE: low), but the confidence interval crosses the line for no effect
- may make little or no difference in health-related quality of life (GRADE: low) and disability (GRADE: moderate)
- may lead to more frequent skin breaks (GRADE: low), but makes little or no difference in falls with injury or fractures
- costs around 1 500 Norwegian kroner per patient
is cost neutral compared with the costs of treating deep vein thrombosis in the short time horizon of 6 months
Deep vein thrombosis (blood clot) is a potential complication in immobile patients with acute stroke. Stroke occurs due to a blood clot in an artery in the brain or after a
haemorrhage where a blood vessel has ruptured. The former is referred to as ischemic stroke and the latter as cerebral haemorrhage. Early mobilization is the best treatment to prevent deep vein thrombosis. When this is not feasible, prophylactic anticoagulant medicines are given, but must be used with caution in cerebral haemorrhages or massive ischemic strokes. Thus, for some patient groups, pharmaceutical thrombosis prophylaxis may be contraindicated. Intermittent pneumatic compression (ICP) is a device with cuffs connected to a pump that provides a pulsating (intermittent) air pressure around the legs. The cuffs are usually placed around both the lower legs and thighs. The medical staff from Haukeland University Hospital with experience with use of the equipment, indicate that it is simple and not time-consuming. The treatment is supposed to prevent deep vein thrombosis.
Bestillerforum RHF, the commissioning forum of the The National System for Managed Introduction of New Health Technologies within the Specialist Health Service in Norway (Nye Metoder), has commissioned the Norwegian Institute of Public Health to conduct a health technology assessment of intermittent pneumatic compression compared with no use of IPC to prevent deep vein thrombosis in immobile patients with acute stroke.
We identified several relevant systematic overviews in an update (carried out in November 2019) of a horizon scanning report from 2016. A guideline from NICE (2018) with a search from 2017 was the most relevant review based on our inclusion criteria and was used as a basis for retrieving studies published before June 2017. We used the search strategies from the NICE report (2018) as a starting point and conducted an updated search for randomized controlled trials published from June 2017 to March 2020. The inclusion criteria were immobile patients with acute stroke who received IPC or IPC plus treatment in the control group compared with standard treatment without IPC or no treatment. The outcomes were distal and proximal venous thrombosis, pulmonary embolism as well as health-related quality of life and adverse events. The risk of bias was assessed for all studies. When calculating effect estimates, we used risk ratio (RR) for dichotomous outcomes, weighted mean difference (MD) for continuous outcomes and calculated 95% confidence intervals (CI). Where possible, we performed subgroup analyses of patients with ischemic stroke and cerebral haemorrhage. We assessed the most important outcomes with the GRADE tool. The certainty of the evidence, i.e. whether we are confident that the effect estimate is close to a true underlying effect, is considered high, moderate, low or very low.
In the health economic assessment, we estimated the average costs of using IPC for prevention of deep vein thrombosis. In addition, we conducted a cost-consequence analysis for the time period of hospitalization. We investigated whether the cost of preventing one case of deep vein thrombosis was higher or lower than treating deep vein thrombosis.
Efficacy and safety
We did not identify any new relevant studies that met our inclusion criteria in the update search. In total, we included three studies in six publications; CLOTS 3 with four publications; 2013, 2014 and two from 2015, Prasad (1982) and Lacut (2005), all included in the report from NICE (2018). In CLOTS 3, IPC (n = 1438) was compared with no IPC (n = 1438) in patients with stroke, both ischemic stroke (n = 1211 vs 1217) and cerebral haemorrhage (n = 187 vs 189). There was no difference between the groups in the proportion of patients receiving prophylactic anticoagulation medicine, but a few more in the no IPC group were treated with heparin. In Lacut (2005), patients with cerebral haemorrhage received IPC plus compression stockings (n = 74) compared with compression stockings (n = 77). Prasad (1982) does not state whether patients had a stroke or cerebral haemorrhage. IPC (n = 13) was compared with no IPC (n = 13). In CLOTS 3 and Lacut (2005) the IPC cuffs were placed around both legs, calves and thighs, while in Prasad (1982) the cuffs were placed around the legs. The main analyses were the comparison of IPC versus no IPC (CLOTS 3 and Prasad, 1982).
For IPC compared to no IPC, we found that deep vein thrombosis, both distal and proximal, measured after 30 days in two studies occurred in 239 of 1451 patients in the IPC group compared with 310 of 1451 patients in the no IPC group (RR = 0 .77 [95% CI: 0.66 to 0.90]). Our confidence in the effect estimate is moderate and the effect is in favour of IPC. We found similar results after six months. Proximal venous thrombosis measured after 30 days in one study occurred in 122 of 1438 patients (8.5%) in the IPC group compared with 174 of 1438 patients (12,1%) in the no IPC group (RR = 0.70 [95% CI: 0.56 to 0.87]) in favour of the IPC group. Our confidence in the effect estimate is moderate. For the subgroups ischemic stroke and cerebral haemorrhage, the results were also in favour of the IPC group (RR ischemic stroke = 0.74 [95% CI: 0.59 to 0.94] and RR cerebral haemorrhage = 0.40 [95% CI: 0, 20 to 0.77]). For pulmonary embolism, we found little or no difference between the groups. Pulmonary embolism occurred in 20 of 1438 patients (1.4%) in the IPC group versus 35 of 1438 patients (2.4%) in the no IPC group; RR = 0.83 (95% CI: 0.51 to 1.35). Our confidence in the effect estimate is low. Mortality after 30 days and after 6 months was possibly lower, but there could also be no difference between the IPC group compared to the no IPC group since the confidence intervals crossed the line for no effect. After 30 days, 157 of 1451 (10.8%) died in the IPC group versus 190 of 1451 (13.1%) in the no IPC group, RR = 0.83 (95% CI: 0.68 to 1.01). After 6 months, the corresponding result was 320 of 1438 (22.3%) versus 361 of 1438 (25.1%), RR = 0.89 (95 % CI: 0.78 t0 1.01). Our confidence in the effect estimates was low. We did not conduct our own analyses of health-related quality of life and disability, but the CLOTS 3 study found little or no difference between the IPC group and the no IPC group. Our confidence in the results for health-related quality of life is low, and for the results for disability it is moderate. Skin breaks may have occurred more frequently in the IPC group (44 of 1438 versus 20 of 1438, RR = 2.15 [1.30 to 3.50]), while we found little or no difference in falls with injury or fractures. Our confidence in the effect estimate for skin damage is low.
The incremental cost of treating one patient with IPC is around 1 500 Norwegian kroner, while treating one case of deep vein thrombosis costs about 32 000 Norwegian kroner. The results from our cost-consequence analysis show that it costs roughly the same to use IPC to prevent one case of deep vein thrombosis as treating one case of deep vein thrombosis. Moreover, the patients are spared for related complications.
Efficacy and safety
Few patients with cerebral haemorrhage were studied. Should these patients or other patients who cannot receive anticoagulation medicines, have a deep vein thrombosis or pulmonary embolism, the treatment options are few. Our results indicate that IPC may be effective in preventing deep vein thrombosis, and experience with it indicates that it is easy to use.
We included only randomized controlled trials. Adverse events and side effects that had been reported only in case studies, studies without control groups and in registry studies, were not identified, and this may be a weakness of our review. The expert group that assisted this report suggested that the use of IPC and its results should be registered in the Norwegian Stroke Register, if the technology is routinely adopted in the Norwegian hospitals.
We did not identify any new studies in the update search. Thus, both this and previous systematic reviews and guidelines are largely based on the results from the CLOTS 3 study. The results in all publications will unavoidably overlap. Whether new studies are needed is not clear.
The results from this health technology assessment indicate that there may be knowledge gaps: IPC may be most relevant for the patient group with cerebral haemorrhage and for other patients for whom prophylaxis with anticoagulants is contraindicated. A broader study of these patient groups may be important.
Our health economic assessment is based on the assumption that the results from the summarized randomized clinical trials are transferable to the Norwegian settings. This assumption creates some uncertainty about local variation when it comes to patient population and clinical practice in Norway.
IPC in immobile patients with acute stroke may reduce the risk of deep vein thrombosis compared to no IPC. The mortality was somewhat lower in the IPC group than in the no IPC group, but there is significant uncertainty associated with the result. Health-related quality of life and function did not appear to differ between the groups, but skin breaks may occur more often in patients receiving IPC. It is roughly equally costly to avoid deep vein thrombosis using IPC, as to treat deep vein thrombosis. Therefore, IPC is a cost neutral intervention in the short time horizon of 6 months. The studies included few patients with cerebral haemorrhage, and it may be relevant to gain more knowledge about the effect of IPC for these patients in further studies. The results in this health technology assessment are mainly based on the results from the CLOTS 3 study and includes the same studies as in the guideline from NICE (2018).