NICE’s recommendations for thromboembolism are not evidence basedBMJ 2011; 343 doi: https://doi.org/10.1136/bmj.d6452 (Published 07 December 2011) Cite this as: BMJ 2011;343:d6452
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In his Personal View published in 2011 , Dr Welfare highlights important points surrounding the use of anticoagulants in the prevention of VTEs and their inclusion in the NICEs guidelines for VTE prevention . We would like to add to his comments our personal review of the evidence supporting the use of mechanical methods of prophylaxis, most commonly translated as graduated compression stockings (GCS).
The 2010 NICE guidelines recommend that all surgical patients start mechanical prophylaxis on admission, continue during their procedure and post-operatively until fully mobile. For medical patients, mechanical prophylaxis should be considered in patients who have a contraindication to pharmacological prophylaxis. NICE makes an exception for stroke patients, who should not be offered mechanical prophylaxis in any circumstances. Mechanical prophylaxis is usually translated in the use of Graduated Compression Stockings (GCS).
NICE largely base their recommendations on evidence from a 2010 Cochrane review (3) and a separate 2009 trial by Dennis et al (4). After review of these publications, we would like to question the certainty with which the Cochrane authors, and subsequently NICE, made their recommendations.
The Cochrane authors included 18 trials encompassing both medical and surgical patients with and without additional background pharmacological prophylaxis against VTE. These trials included on average 140 patients (range of 18 to 252 patients). The Cochrane authors excluded two large trials, one in 2518 stroke patients (4) and one in 874 orthopaedic patients (5). Reasons for exclusion were that the population was too speciifc for the former and the study too pragmatic for the later. Both of these trials did not support the use of GCS. In 6 of the 18 included trials, CGS were applied only to one leg, with the patient’s other leg acting as a control, a fact known to impede blood flow in both legs (6). All of the trials included in the Cochrane review had detection of VTE as their primary outcome, which were detected radiologically by scanning patients on set days.It is unclear whether or not the patients with the VTEs were symptomatic or asymptomatic, an important fact when the significance of asymptomatic VTEs is uncertain (7). The authors identified 10 of the 14 trials (out of a total of 18) that had received some form of support from stocking manufacturers, ranging from simply supplying the stockings to outright sponsoring the study. Finally, the Cochrane authors decided to part from the Cochrane guidelines when considering publication bias, and provided 2 funnel plots to conclude that no bias was present. We repeated this simple statistical exercise using the Cochrane guidelines and our findings are different (Figures a, b) indicating a statistical bias may well have misled their conclusion that “GCS are effective in diminishing the risk of DVT in hospitalised patients”.
NICE chose to consider both the Cochrane review and one of the study rejected by the Cochrane authors. Including this trial formed the basis that GCS should not be used in stroke patients. NICE does not comment if this conclusion might also apply (or why it would not) to the medical patients included in the studies reviewed by the Cochrane authors, neither does it comment if the inclusion of that study in the statistical analysis would have modified their conclusion.
Both NICE and Cochrane acknowledge that none of the individual trials, or the Cochrane analysis, are statistically powerful enough to see any differences in more clinically important outcomes such as all-cause mortality and pulmonary embolus.
In conclusion, we believe that NICE’s recommendation on GCS should be reviewed. Given the low confidence in any potential benefit it is important that any recommendation does not prevent research required to establish the validity of GCS in routine clinical practice for both medical and surgical patients,. The cost associated with these measures is considerable, and the benefits are uncertain.
Figures a, b. Funnel plots are a way to consider publication bias (8). In figure a, the Cochrane authors created two separate funnel plots with 8 and 10 studies respectively. They concluded on that basis that there was no publication bias. In figure b, we plotted all the studies in one funnel plot, and the plot indicates a possibility of publication bias. Our method is in line with the Cochrane review guidance (8), whilst the one used by the authors is not.
Dr Laurence Whittaker
Foundation Year 1 Doctor
County Durham and Darlington NHS Foundation Trust, Hollyhurst Road, Darlington DL3 6HX
Dr Trevor Baglin
Divisional Director of Pathology & Consultant Haematologist
Box Number: 234, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust
Hills Rd, Cambridge CB2 0QQ
Dr Alain Vuylsteke
Consultant in Anaesthesia and Intensive Care
Department of Anaesthesia and Intensive Care, Papworth Hospital NHS Foundation Trust, Cambridge CB23 3RE
1. Welfare M. NICE’s recommendations for thromboembolism are not evidence based. BMJ 2011;343:d6452
2. National Institute for Health and Care Excellence. Venous thromboembolism: reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in patients admitted to hospital. CG92. London: National Institute for Health and Clinical Excellence;2010
3. Sachdeva A, Dalton M, Amaragiri SV, Lees T. Elastic compression stockings for prevention of deep vein thrombosis. Cochrane Database Syst Rev. [online] 2010(7). Available from DOI 10.1002/14651858.CD001484.pub2 [date of access 24/04/13]
4. Dennis M, Sandercock PA, Reid J, Graham C, Murray G, Venables G, et al. Effectiveness of thigh-length graduated compression stockings to reduce the risk of deep vein thrombosis after stroke (CLOTS trial 1): a multicentre, randomised controlled trial. Lancet. 2009 Jun 6;373(9679):1958-65
5. Cohen AT, Skinner JA, Warwick D, Brenkel I. The use of graduated compression stockings in association with fondaparinux in surgery of the hip. A multicentre, multinational, randomised, open-label, parallel-group comparative study. J Bone Joint Surg Br. 2007 Jul;89(7):887-92
6. Spiro M, Roberts VC, Richards JB. Effect of externally applied pressure on femoral vein blood flow. Br Med J. 1970 Mar 21;1(5698):719-23
7. Kim YH, Oh SH, Kim JS. Incidence and natural history of deep-vein thrombosis after total hip arthroplasty. A prospective and randomised clinical study. J Bone Joint Surg Br. 2003 Jul;85(5):661-5
8. Sterne JAC EM, Moher D (ed.). Chapter 10: Addressing reporting biases. In: Higgins JPT, Green S (ed.) Cochrane Handbook for Systematic Reviews of Intervention. Version 5.1.0 (updated March 2011). The Cochrane Collaboration. 2011; Available from www.cochrane-handbook.org [date of access 24/04/13
Competing interests: No competing interests
We read the recent article on thromboembolism with interest. The author highlighted that the headline figure of 25,000 preventable deaths due to VTE equates to an expected one in 24 deaths across the UK and asserted these figures were inflated four times when compared to only 6500 deaths reported as caused by VTE out of around 600,000 deaths due to all causes (1 in 92 deaths). In North Lancashire, there were 374 deaths due to VTE (main and underlying cause of death with ICD 10 codes ICD codes: I269, I269, I801, I802, I803, I809, I829) out of 18797 deaths between September 2006 and August 2011 (1 in 50 deaths). Although this non standardised death rate in North Lancashire is higher than the national average, it is only half the number of expected deaths based on national estimates. Or, VTE is not recorded as a cause of death in one in two patients dying due to VTE.
Our analysis of hospital admissions with VTE as primary or secondary diagnosis across Lancashire between Jan 2009 and April 2011 showed that around six out of every 1000 spells were due to VTE. This proportion has been stable and predictable. We did not find a shift or trend in the proportion of VTE spells since the introduction of national CQUIN for VTE in June 2010, suggesting the national policy so far has not led to a measurable improvement in VTE outcomes and the current prevention efforts are not enough for achieving further improvements in VTE outcomes. Both these explanations question the status quo nature of national and local VTE policies. We wonder if it is time for a rethink about the national CQUIN scheme for VTE risk assessment, to widen the scope to collect data on VTE thromboprophylaxis as part of the NHS Outcomes Framework, and improve the recording of VTE related deaths.
1. BMJ 2011;343:d6542
Competing interests: No competing interests
Dr Mark Welfare, in his personal view piece “NICE’s recommendations for thromboembolism are not evidence based”, makes several valid observations, particularly about the lack of good quality evidence in some areas and the need for more research to address this. The prophylaxis of venous thrombo-embolism is not alone in lacking top grade evidence; it is alarming how many apparently tried and tested therapies fail that test when a proper search is made for proof. We agree there is a lack of randomised trial data in the field of VTE prophylaxis for general medical in-patients, despite the fact that expert systematic reviewers provided all the findable evidence and the Guideline Development Group made every effort to examine the evidence that was available. It is matter of record that when the CLOTS Trial Collaboration report findings on DVT prophylaxis in stroke patients  we stalled the publication of our guidance, met to reconsider, and changed our guidance in the light of this most recent evidence.
Dr Welfare takes the guideline developers to task on the use of surrogate endpoints and, in principle, he is right to do so. If there were ample randomised evidence with the important endpoints of fatal bleeds versus fatal embolism they would have used that alone. As he says, there is insufficient evidence. The Guideline Development Group paid particular attention to whether asymptomatic DVT was a surrogate or whether there was in fact a continuum and revisited the question several times during the development of the guidance. The GDG studied the point specifically and found that where both the major and lesser outcomes were available there was a proportionality which ran through individual studies and their meta-analyses. There are underpinning biological reasons to believe in a common cause hypothesis for DVT and pulmonary embolism and there are empirical reasons to believe that Heinrich’s triangle applies in the relationship between venous thrombosis and death from pulmonary embolism. We therefore decided to take the line that there was a continuum between fatal PE and asymptomatic DVT and if lower limb thrombosis was reduced that would translate into lives saved from PE. The NICE GDG is not alone in taking this approach. This is imperfect, but better to use the evidence available than waste it. Some unbiased evidence is better than none. As and when new evidence becomes available, NICE will assess it.
Unfortunately Dr Welfare then departs from cogently reasoned argument by implying that the guideline developers were in the pocket of pharma and that, by implication, NICE was acquiescent in putting its name to a deliberately flawed guideline. The gentlest interpretation is that Dr Welfare has an incomplete understanding of how NICE guidelines are developed. Be that as it may, the Guideline Development Group members, unfairly accused by Dr Welfare, might be owed an apology. Dr Welfare’s use of the fact that Boehringer Ingelheim issued a press release on behalf of Lifeblood without its consent as proof of complicity between the two is similarly unconsidered as evidenced by his omission of the fact that Lifeblood reported Boehringer to the ABPI over the matter.
We have to defend our reputations against the implication that an independent Guideline Development Group could be so easily suborned by self-interest and that due vigilance on behalf of each other was not exercised. Every meeting started with a rigorous update on conflicts of interest and an interrogation by the chair where there was any doubt. It is quite natural that leaders in the field also are involved in funded meetings and help with clinical trials of pharmaceutical products but during the work of the GDG we ensured that they distanced themselves from these involvements.
Competing interests: Memebr of NICE CG92 group
I thank the wide interest in my Personal View, the format of which did not allow detailed examination of the evidence and further positive suggestions. The polemical style has perhaps seemed to polarise views more than need be. I note the general support from day to day clinicians.
Lifeblood have made detailed comments which I would like to respond to and amplify. Firstly I do not doubt the individual sincerity of Lifeblood members and NICE members. That is not the way Pharma works. Rather they use the 'food, flattery and friendship plus funding' route so eloquently described by Peter Grant.
A further good example of the work of Pharma is paradoxically given within Lifeblood's response. My inability to understand where the 2005 claims of 25,000 preventable deaths was because the reference now given where it originated was published two years later in 2007 (The VITAE study, Cohen et al, 2007)! The paper declares that ‘The VITAE study was funded by sanofi-aventis. The model structure and underlying data were approved by an independent expert board. Editorial assistance was provided by sanofi-aventis’. Detailed analysis of the VITAE study shows that the claims that 60,000 people in the UK die of VTE each year is based on just one epidemiological study from France and an algorithm which purports to describe the relationship between DVT (symptomatic and undiagnosed) and PE (detected and otherwise). The study then uses four layers of projection to achieve its inflated claim. As Lifeblood's response indicates, the 25,000 prevented deaths would require prophylaxis to be 66% effective at preventing death from VTE which it clearly is not. Whilst I agree that diagnosis of PE is difficult, death is a fairly robust end-point.
The central claim of the policy is that 25,000 deaths will be prevented. This key claim cannot be maintained and should be dropped. Only direct high quality meta-analysis can give us the answer to whether deaths can be prevented - NICE's own study showed that in medical patients it probably cannot with current medications. Projections and data from unrelated post-mortem studies are interesting but do not show that death can be prevented.
DVT, principally asymptomatic, is prevented but that is not the claim of NICE. I could support a campaign that advertised itself as 'preventing 25,000, largely asymptomatic, DVTs', but that is not quite so catchy.
Then what about harms - a recent further meta-analysis of prophylaxis in medical patients (Ann Intern Med2011;155:602-15) suggests that for every 1000 medical and stroke patients given LMWH, 3 symptomatic PEs will be prevented but at the expense of 4 major bleeds with no conclusive effect on death. Lifeblood emphasise the reduction in suffering from preventing DVT whilst ignoring the 'suffering' from major bleeds some of which are intra-cerebral. It should also be pointed out that trials only recruited patients with lo risk of bleeding so arguing that careful case selection will prevent these bleeds is superfluous - the trial data with an excess of bleeding apply to low risk populations.
It would be interesting to read the quality of patient information leaflets relating to the decision to accept prophylaxis and how they express these data.
NICE should review their guidance in the light of this new evidence and the widespread concern about the policy amongst clinicians. My central thesis is that the potential of preventing deaths from VTE will almost certainly not be fulfilled using current recommendations and that we should begin a search for new strategies from a blank sheet using a wider range of expert input.
If we can accept that at current state of knowledge, lmwh may not prevent VTE, what other strategies could be used? these are strategies I conceived with just 10 minutes thought:
• Routine scanning of all patients admitted at some pre-determined point (3-5 days seems reasonable) to look for asymptomatic DVT and giving treatment dose after that. This would ensure that treatment was targeted at the highest risk patients but with a risk that it would be too late for some
• Further studies of high dose aspirin in high risk patients given that aspirin seems to show promise in some studies but because it is not a patent protected drug has been poorly studied in this context
• A trial with death or symptomatic PE as end point - sample size calculation (http://www.sealedenvelope.com/power_binary.php) suggests that with 90% certainty and 0.05 significance level, just 68,424 patients would need to be randomized to test the hypothesis that prophylaxis improves survival from 96% (hospital survival in Stein) to 95.5%. If survival advantage is better, 18,058 patients would be required in each arm to examine improvement from 96% to 95%. If the calculations put forward by NICE etc are used, 15% of patients in the trials died and 10% of deaths were due to VTE and treatment was 50% protective, this would imply a reduction in mortality from 15% to 14.25%, then 107274 patients would need to be randomized but if survival was improved by 1% to 86% then 52112 would be required.
• Further studies of the best length of treatment for LMWH. Many of the studies (e.g Prevent which examined effectiveness of Dalteparin) used treatment until discharge or 14 days of treatment as a minimum even if discharged before. Currently the policy being implemented means that in reality patients get treatment only whilst an in-patient and mean length of stay is 5.5 days – we may well be implementing an ineffective regime at present
• Various strategies based on early mobilization, foot exercises, early discharge etc could be assessed and whilst having cost implications they would have few side effects. Similarly, approaches to reduce admissions rates and offer ambulatory care at home could be effective. Length of stay has reduced considerably since the main studies were conducted.
• Concentrate on better diagnosis of VTE. Currently there are clearly some patients dying of PE after presenting to doctors and being misdiagnosed. Better training, more routine use of risk scores and D-dimer tests in primary and secondary care, lower thresholds for performing CT pulmonary angiography and Doppler of legs and better monitoring of respiratory rate and hypoxia in primary care could all be useful strategies. One starting point would be an analysis of the deaths of patients where PE has been missed.
• Many medical patients are readmitted within 90 days and many have ongoing risk for VTE irrespective of admission. In the high risk patients (e.g. cancer, chronic inflammation) consideration should be given to long term prophylactic strategies
I would like the debate on VTE prophylaxis to move forward. I hope that my article, through its polemical approach, has initiated new debate which will be accepted by NICE and all interested parties can move forward together on this important subject
Competing interests: as before
We were disappointed by Dr. Mark Welfare’s insinuation that Lifeblood: The Thrombosis Charity is controlled by big pharma and would like to clarify this and other misconceptions and inaccuracies contained in his personal view (1).
Lifeblood has always striven to be independent of the pharmaceutical companies. Our annual accounts ending on 31/1/11 filed at the Charity Commission, showed that 58% of our income is derived from public donations. We do receive funding from pharmaceutical companies, however we always ensure the funds are ring-fenced for educational / awareness projects. They are mainly directed towards our annual awareness campaign, “National Thrombosis Week”. Any pharma donations are only accepted on the basis that Lifeblood controls these projects. Similarly we do not endorse any products, and have taken a responsible stance with the new anticoagulants, advising they should only be used where there is an evidence base and there are licensed indications (see www.thrombosis-charity.org.uk).
It is true that in 2008 an errant journalist employed by an agency paid by Boehringer Ingelheim issued a press release timed to coincide with the launch one of the new oral anticoagulants. The article erroneously and irresponsibly suggested that Lifeblood endorsed the drug and hailed it as an alternative to warfarin. This was done without Lifeblood’s knowledge and consent. Furthermore Lifeblood reported Boehringer Ingelheim to the Prescription Medicines Code of Practice Authority for breaching the Code of Practice of the Association of the British Pharmaceutical Industry (ABPI), and the company was appropriately admonished.
We have worked hard alongside health professionals and are proud to have shared responsibility for bringing the failure to prevent hospital-acquired venous thromboembolism (VTE) to the attention of the Health Select Committee in 2004, and to precipitate an enquiry. This, and continued lobbying from ourselves, health professionals and the All Party Parliamentary Thrombosis Group, led to the development of the Department of Health’s comprehensive approach which included new NICE guidelines (CG92) and the CQUIN VTE targets.
Dr. Welfare admitted he didn’t understand the basis of the figure of 25,000 preventable deaths due to hospital-acquired VTE. It may assist readers to know that it comes from data on file from the VITAE study, by Dr. A Cohen et al (2). This looked at six European countries and full country specific data were used in the UK calculations. It was a modified incidence based model, which took into account HES data, prophylaxis rates and published event rates. He found a conservative mortality figure for the UK was approximately 60,000 deaths and 42,000 being hospital related. Of these 20% might be terminally ill, leaving approximately 34,000 with survival prospects. Of these assuming a 50% recommended prophylaxis rate (medicine and surgery combined) and a two-thirds reduction in pulmonary embolism (PE mortality), then there are 25,000 deaths which are potentially preventable with prophylaxis. In support of this estimate, the last statistics on death in England and Wales where PE was mentioned on the death certificate were 16,670 in 2007 (National Statistics office). One of the problems with the death rate due to PE is that PE is grossly under-diagnosed. For example a post mortem study of hospital deaths in Cambridge showed that for every PE diagnosed in life, another two cases were not recognised antemortem (3). Thus applying this principle to the death rate in England and Wales, and allowing for the fact that a proportion of patients do receive thromboprophylaxis in hospital and therefore have their deaths prevented, would support the VITAE data.
Dr. Welfare argues we shouldn’t be using thromboprophylaxis in medical patients because there is no evidence it reduces death. He does concede there is a reduction in morbidity, i.e. in deep vein thrombosis but then criticizes the use of any surrogate marker. However the logic of using incidence of DVT (after all it is the usual cause of a PE) as a surrogate marker for PE cannot be denied. Furthermore reduction in morbidity, including post thrombotic syndrome, is of benefit to patients. Should health professionals only use medication if there is a proved reduction in death in clinical trials? Should we not also reduce suffering? Certainly the patient body we represent believes so.
Dr. Welfare suggests that “litigation costs will rise if patients who experience VTE after admission to hospital have not been given prophylaxis; and that Trusts will be fined …if they do not comply with the requirements to assess more than 90% of admissions”. Rather than supporting his argument for the removal of compulsory implementation of appropriate thromboprophylaxis, this makes a very cogent case for delivery of this important patient safety initiative. It is regrettable that Dr. Welfare feels that “there are many better things [he] could be concentrating on” and that Trusts who do not comply with the CQUIN target are losing money. However we note that his Trust finally achieved the CQUIN target of 90% for the first time in the second quarter of 2011-12, and so will not be losing money and we congratulate them on this.
Lastly Dr. Welfare suggests that the box for preventing VTE has been ticked and therefore “further research ideas will not be pursued, and political and clinical momentum will be lost”. However implementing the CQUIN targets has been difficult for many Trusts and has exposed issues that will stimulate more research. For example there is a lack of evidence for many groups of patients classed as “medical” and is thromboprophylaxis required in those wearing plaster casts? Moreover there is not yet a perfect pharmacological thromboprophylactic agent as he highlights.
On a more positive note, we thank Dr. Welfare for his support of the Lifeblood “Spot the Clots” Campaign. Again it may interest readers to know that far from being new, the campaign was conceived in 2010 and has been a main focus of the charity for a little short of two years. It is the product of numerous phone calls and e-mails to the charity by patients and relatives of those who have suffered or died of venous thromboembolism, where the diagnosis has been “missed” by health professionals.
Lifeblood is proud of its involvement in important patient safety initiatives, and this has been recognized by the Charity Awards with the “Healthcare and Research Charity of the Year” in 2010.
1. Welfare M. NICE’s recommendations for thromboembolism are not evidence based. BMJ 2011; 343: d6452
2. Data on file from: Cohen AT, Agnelli G, Anderson FA, Arcelus JI, Bergqvist D, Brecht JG, Greer IA, Heit JA, Hutchinson JL, Kakkar AK, Mottier D, Oger E, Samama MM, Spannagl M; VTE Impact Assessment Group in Europe (VITAE). Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality.Thromb Haemost 2007 Oct;98(4):756-64.
3. Baglin TP, White K, Charles A. Fatal pulmonary embolism in hospitalised medical patients. J Clin Path 1997; 50 (7): 609-10.
Competing interests: Lifeblood: The Thrombosis Charity exists to increase awareness and improve management of thrombosis. Lifeblood has always striven to be independent of the pharmaceutical companies. Our annual accounts ending on 31/1/11 filed at the Charity Commission, showed that 58% of our income is derived from public donations. We do receive funding from pharmaceutical companies, however we always ensure the funds are ring-fenced for educational / awareness projects. They are mainly directed towards our annual awareness campaign, “National Thrombosis Week”. Any pharma donations are only accepted on the basis that Lifeblood controls these projects. Similarly we do not endorse any products, and have taken a responsible stance with the new anticoagulants, advising they should only be used where there is an evidence base and there are licensed indications.
The authors of the current NICE guidelines on venous thromboembolism (VTE) have produced a comprehensive and apparently authoritative review of the evidence supporting VTE prophylaxis (1) . While application of many of their recommendations will undoubtedly save lives and reduce VTE-associated morbidity, we remain unconvinced as to the strength of the case to continue VTE prophylaxis for 28 days after colorectal cancer resection.
This represents a fundamental alteration in practice across primary and secondary care for tens of thousands of patients per year in the UK. We suspect that many, possibly the majority of organizations will routinely choose to ignore this advice, and not without justification.
The guideline development group (in which expertise in the surgical management of abdominopelvic malignancy was notable by its absence) proposes this change in practice based principally on three publications that, even when combined, describe the prevention of only 4 episodes of pulmonary embolism in almost 400 patients( 2-4). Even extending the analysis to those patients with proximal deep venous thromboses indicate that only 13 episodes would have been prevented by extending prophylaxis to 28 days, and, since 11 of these were reported in a study in which approximately 50% of patients did not even have malignant disease (4), the relevance of this finding to colorectal cancer (or indeed other abdominopelvic surgery for malignancy) remains unconvincing.
Furthermore, reliance on these three studies, the most recent of which completed recruiting patients almost a decade ago, fails to take into account recent developments such as enhanced recovery protocols and laparoscopic surgery, which have transformed postoperative recovery, reducing the postoperative stress response, immobility and length of stay, all of which would be expected to have a significant bearing on the risk of postoperative VTE.
We anticipate that the uncritical application of these guidelines will put acute NHS trusts and PCT’s (or GP consortia) at loggerheads over precisely who funds extended VTE prophylaxis and will inevitably attract criticism of surgical practice that omits extended prophylaxis, in the event that a patient develops a venous thromboembolism within 28 days of discharge from hospital. Finally, for an elderly cancer population, there is the additional practical difficulty of administration of extended VTE prophylaxis; the guidelines development group acknowledge that post discharge prophylaxis may not be cost effective if more than 37% of patients needed district nurses to administer this therapy.
We believe that there is simply insufficient evidence in these guidelines to justify the major upheaval in clinical practice required to extend VTE prophylaxis to 28 days for the 20,000 patients each year undergoing colorectal cancer resection. Updating guidelines regularly is clearly important, but such substantial changes to clinical practice must be justified on the basis of new and definitive evidence, which is currently lacking.
Gordon Carlson - Professor of Surgery & Consultant Colorectal Surgeon, Salford Royal Hospitals, Salford Royal NHS Foundation Trust
Brendan Moran - Consultant Colorectal Surgeon & Chairman Multidisciplinary Clinical Committee, Association of Coloproctology of Great Britain & Ireland
Nigel Scott - Consultant Colorectal Surgeon & President Association of Coloproctology of Great Britain & Ireland
Graham Williams - Consultant Colorectal Surgeon & President Elect Association of Coloproctology of Great Britain & Ireland
1. Venous thromboembolism: reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in patients admitted to hospital. http://www.nice.org.uk/nicemedia/live/12695/47920/47920.pdf. NICE 2010
2. Lausen I, Jensen R, Jorgensen LN, Rasmussen MS, Lyng KM, Andersen M et al. Incidence and prevention of deep venous thrombosis occurring late after general surgery: randomised controlled study of prolonged thromboprophylaxis. European Journal of Surgery 1998, 164(9):657-63.
3. Bergqvist D, Agnelli G, Cohen AT, Eldor A, Nilsson PE, Le Moigne-Amrani A et al. Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. New England Journal of Medicine 2002, 346(13):975-80.
4. Rasmussen MS, Jorgensen LN, Wille-Jorgensen P, Nielsen JD, Horn A, Mohn AC et al. Prolonged prophylaxis with dalteparin to prevent late thromboembolic complications in patients undergoing major abdominal surgery: a multicenter randomized open-label study. Journal of Thrombosis and Haemostasis : JTH 2006, 4(11):2384-90.
Competing interests: No competing interests
Mark Welfare's review of the evidence for what has become ritualistic behaviour in most hospitals is timely. I work within a specialty (Stroke Medicine) that does not routinely use low molecular weight heparin or compression stockings precisely because the evidence does not favour their use. In fact the most recent Cochrane review of anticoagulation in acute stroke shows any benefit in prevention of VTE was offset by harm associated with haemorrhage(1). Two recent randomized controlled trials have found that the use of compression stockings is not associated with clinical benefit(2,3).
The current status quo, whereby the majority of hospitalized patients are treated with either anitcoagulants and/or compression stockings is a very lucrative one for ‘Big Pharma’. This is perhaps why Boehringer Ingelhem is amongst sponsors contributing to Lifeblood, whose accounts for the year to Jan 2011* showed £75K in corporate donations. In its capacity as a stakeholder organization, a representative of Anticoagulation Europe (another charity dedicated to the prevention of thrombosis) championed Dabigitran Etexilate in its submission to NICE during the early appraisal process†. Anticoagulation Europe receives funding from Boehringer Ingelheim amongst others. Its accounts show that it received total sponsorship, subscriptions excluded, in excess of £123K to year end 2010‡.
The good intentions of these charitable organizations is not in question. However we now seem to be living in an era when decision makers within the NHS are increasingly required to give almost equal weighting to clinical evidence and ‘stakeholder’ opinion. ‘Big Pharma’ has correctly deduced that supporting patient groups and charitable organizations is a neat way to sidestep the regulations prohibiting direct-to-patient marketing. In this setting it is vital that clinicians keep their critical faculties honed, and do not conflate enthusiastic advocacy with evidence.
*Accessed Dec 2011 at http://www.charity-commission.gov.uk/Accounts/Ends40/0001090540_ac_20110...
†Accessed Dec 2011 at http://www.nice.org.uk/nicemedia/live/12225/55939/55939.pdf
‡Accessed Dec 2011 at http://www.charity-commission.gov.uk/Accounts/Ends50/0001090250_ac_20101...
1. Sandercock P, Counsell C, Kamal AK. Anticoagulants for Acute Ischemic Stroke. Stroke. 2009 Jun. 29;40(7):e483–e484.
2. Collaboration TCT. Effectiveness of thigh-length graduated compression stockings to reduce the risk of deep vein thrombosis after stroke (CLOTS trial 1): a multicentre, randomised controlled trial. The Lancet. 2009 Jun. 6;373(9679):1958–1965.
3. CLOTS (Clots in Legs Or sTockings after Stroke) Trial Collaboration. Thigh-length versus below-knee stockings for deep venous thrombosis prophylaxis after stroke: a randomized trial. Ann Intern Med. 2010 Nov. 2;153(9):553–562.
Competing interests: No competing interests
I read the excellent article by Dr Welfare with great interest (1) and he makes an excellent point concerning the dangerous bandwagon that is the Pharmaceutical industry’s push for more and more aggressive chemical thromboprophylaxis.
The number of so called ‘preventable’ fatal thromboembolic events has been grossly exaggerated by politicians, the pharmaceutical industry, NICE and by others with vested interested including certain clinicians and charities (2). The scientific evidence has been butchered by politically driven ignorance.
There is increasing evidence emerging that more aggressive newer anticoagulants have no significant benefits over older cheaper drugs in terms of preventing thromboembolic events (4), while they will inevitably result in a significant morbidity and mortality in terms of their haemorrhagic side effects.
The sad thing is that the current box ticking NHS approach to thromboprophylaxis combined with the dubious NICE VTE guidelines are not going to help patients, they are arguably ineffective and will probably result in more harm than good.
1. Mark Welfare. NICE’s recommendations for thromboembolism are not evidence based. BMJ 2011;343:d6452
2. BJF Dean. The impact of national guidelines for the prophylaxis of venous thromboembolism on the complications of arthroplasty of the lower limb. J Bone Joint Surg Br 2010 92-B: 747-748.
3. Samuel Z. Goldhaber et al. Apixaban versus Enoxaparin for Thromboprophylaxis in Medically Ill Patients. New England Journal of Medicine 2011 Nov 13th.
4. Jameson et al. The effect of aspirin and low-molecular-weight heparin on venous thromboembolism after hip replacement. Journal of Bone and Joint Surgery - British Volume, Vol 93-B, Issue 11, 1465-1470.
Competing interests: No competing interests
If I get a penny for every VTE form I do, I would retire before having to apply for a consultant job. I am currently struggling to understand the rationale behind having to consider VTE prophylaxis for day case stress echo patients in our department. These are patients who hardly stay for an hour. I am having to prepare a new drug chart purely to tick the VTE box off as many get exercise stress echos and are not prescribed any drug. The patients are anything but immobile and the drug charts obviously don't come free. Of course, I tick the box in question and put a comment saying that prophylaxis wasn't prescribed as the patient attended for a day case echo. I am often hunted down by the nurses if I forget. Going at this rate, we may be may be asked start doing these forms for outpatients, as they often wait for well over an hour. Are we going over the top?
Competing interests: No competing interests
We operate under the principle that ‘we need clinical experts in the field to develop guidelines’. But because of the pervasive and persuasive nature of contact between these experts and pharma – ‘food, flattery and friendship’ plus funding – we risk getting expert opinion based, instead of evidence based guidelines.
If there are no uncompromised experts in the relevant field we may be better served if guideline developers were only method experts, with or without uncompromised clinicians in a different specialty from the guideline. The real clinical experts could then make their input during the public consultation phase, at which time their views would be subject to scrutiny of their argument, not respect for their opinion.
Requiring a conflict of interest be declared does not remove its potential bias. It simply shifts its burden to the end user. Quite unhelpful.
Competing interests: No competing interests