A Nation-wide Initiative against Venous Thromboembolism

There is a gap between knowledge and recommendations regarding venous thromboembolism (VTE) on the one hand and daily practice on the other. This fact has prompted a Swiss multidisciplinary group consisting of angiologists, haematologists, internists, and emergency medicine and pharmaceutical medicine specialists interested in VTE, the SAMEX group, to set up a series of surveys and studies that give useful insight into the situation in our country. Their projects encompassed prophylactic and therapeutic aspects of VTE, and enrolled over 7000 patients from five academic and 45 non-academic acute care hospitals and fifty-three private practices in Switzerland. This comprehensive Swiss Clinical Study Programme forms the largest database surveying current clinical patterns of VTE management in a representative sample of the Swiss patient population. Overall the programme shows a lack of thromboprophylaxis use in hospitalised at-risk medical patients, particularly in those with cancer, acute heart or respiratory failure and the elderly, as well as under-prescription of extended prophylaxis beyond hospital discharge in patients undergoing major cancer surgery. In regard to VTE treatment, planning of anticoagulation duration, administration of LMWH for cancer-associated thrombosis, and the use of compression therapy for prevention of post-thrombotic syndrome in patients with symptomatic proximal DVT require improvement. In conclusion, this programme highlights insufficient awareness of venous thromboembolic disease in Switzerland, underestimation of its burden and inconsistent application of international consensus statement guidelines regarding prophylaxis and treatment adopted by the Swiss Expert Group.


Summary
There is a gap between knowledge and recommendations regarding venous thromboembolism (VTE) on the one hand and daily practice on the other.This fact has prompted a Swiss multidisciplinary group consisting of angiologists, haematologists, internists, and emergency medicine and pharmaceutical medicine specialists interested in VTE, the SAMEX group, to set up a series of surveys and studies that give useful insight into the situation in our country.Their projects encompassed prophylactic and therapeutic aspects of VTE, and enrolled over 7000 patients from five academic and 45 non-academic acute care hospitals and fifty-three private practices in Switzerland.This comprehensive Swiss Clinical Study Programme forms the largest database surveying current clinical patterns of VTE management in a representative sample of the Swiss patient population.
Overall the programme shows a lack of thromboprophylaxis use in hospitalised at-risk medical patients, particularly in those with cancer, acute heart or respiratory failure and the elderly, as well as under-prescription of extended prophylaxis beyond hospital discharge in patients undergoing major cancer surgery.In regard to VTE treatment, planning of anticoagulation duration, administration of LMWH for cancer-associated thrombosis, and the use of compression therapy for prevention of post-thrombotic syndrome in patients with symptomatic proximal DVT require improvement.In conclusion, this programme highlights insufficient awareness of venous thromboembolic disease in Switzerland, underestimation of its burden and inconsistent application of international consensus statement guidelines regarding prophylaxis and treatment adopted by the Swiss Expert Group.

Introduction
The best estimates indicate that 350 000 to 600 000 Americans annually suffer from venous thromboembolism (VTE), and that at least 100 000 deaths may be directly or indirectly related to this disease.As stressed in a Call to Action of the US Surgeon General in 2008 [1], this is far too many, since many of these deaths could be avoided.The US Institute of Medicine has classified the failure to provide hospitalised, at-risk patients with appropriate screening and preventive treatment as a medical error, and the US Agency for Healthcare Research and Quality has ranked the provision of such preventive treatment as one of the most important things that can be done to improve patient safety.Proven, effective measures are available to prevent and treat deep vein thrombosis (DVT) and pulmonary embolism (PE) in high-risk individuals.Yet today a substantial proportion of individuals who could benefit from such proven services do not receive them.
Obviously there is a gap between knowledge and recommendations [2] on the one hand and daily practice on the other.Thus, the global ENDORSE survey showed that 59% of hospitalised at-risk surgical patients and 40% of at-risk medical patients were given appropriate thromboprophylaxis [3].These data prompted a Swiss multidisciplinary group consisting of angiologists, haematologists, internists, and emergency medicine and pharmaceutical medicine specialists interested in VTE -the SAMEX Group -to convene once a year between 2006 and 2011 to discuss ways of closing this gap.They did more than just discuss, since their yearly meeting ended with a series of surveys and studies that provide useful insight into the situation in our country (table 1) [4][5][6][7][8][9][10][11].Their projects encompassed prophylactic and therapeutic aspects of VTE, and enrolled over 7000 patients from five academic, 45 non-academic acute care hospitals and fifty-three private practices in Switzerland.Overall, 76% of the patients were recruited in the Germanand 24% in the French-speaking part of Switzerland, while 40% of the patients were enrolled in academic and 60% in non-academic centres.
In the present review we aim to summarise the results of the prospective comprehensive Swiss Clinical Study Programme in a meaningful conclusion which will alert and specifically advise physicians with a view to improvement of current VTE management in Switzerland.

Current consensus guidelines
According to the consensus guidelines of the American College of Chest Physicians (ACCP) [2] endorsed and commented on by the Swiss Expert Group (SEG) [12], all hospitalised medical and surgical patients should be systematically assessed for the presence or absence of VTE risk factors, and thromboprophylaxis is indicated in patients at high risk (grade 1A).Grade 1 and Grade 2 refer to the risk to benefit balance that is either clear (grade 1) or unclear (grade 2), whilst the suffixes A to C refer to the quality of evidence (A high, B intermediate, and C poor quality) [13].After hospital discharge, extended prophylaxis for up to 35 days after surgery in patients with total hip replacement or fracture (grade 1A), knee replacement (grade 2B), and major cancer surgery (grade 2A) is recommended.
In patients with acute VTE, initial parenteral anticoagulation with unfractionated heparin, low-molecular-weight heparin (LMWH), or fondaparinux is indicated (grade 1A) for at least 5 days and until the target INR is reached for ≥24 hours (grade 1C), followed by administration of vitamin K-antagonist (VKA).Three-month anticoagulation with VKA is recommended for the treatment of provoked VTE (grade 1A) or first isolated distal DVT (grade 2B), and indefinite-duration anticoagulation should be considered for patients with unprovoked proximal or unprovoked recurrent VTE (grade 1A).The risk-benefit ratio of indefinite-duration anticoagulation shall be periodically evaluated (grade 1C).In patients with acute cancer-associated VTE, the recommendation mandates anticoagulation therapy for an indefinite duration or until the cancer is resolved, and the recommended modalities include LMWH for 3-6 months (grade 1A), followed by VKA or LMWH for patients with active cancer (grade 1C).In patients with symptomatic proximal DVT, the use of elastic compression stockings or bandages is recommended for a minimum of 2 years to prevent post-thrombotic syndrome (grade 1A).

Thromboprophylactic aspects
In the Swiss ENDORSE survey [4], 2000 patients were included of whom 1153 (58%) were in surgical wards and 847 (42%) in medical wards.According to the ACCP criteria [2], the proportion of surgical patients at VTE risk was similar in Switzerland (68%, between hospital range 48-86%) in comparison with the global ENDORSE study [3] (64%) (p = 0.296).The rate of at-risk medical patients was lower in Switzerland (21%, range 3-44%) than in the global study (42%) (p<0.001).The proportion of at-risk surgical patients with ACCP-recommended VTE prophylaxis was higher in Switzerland (81%, between-hospital range 76-93%) than in the global study (59%) (p<0.001).Among medical patients at risk, the use of recommended thromboprophylaxis was higher in Switzerland (61%, between-hospital range 0-84%) than in the global survey (40%) (p<0.001).However, 56% of the patients with cancer, 41% with major trauma, and 29% undergoing vascular surgery received no prophylaxis.Briefly, in Switzerland, although the rate of recommended thromboprophylaxis was higher than in many countries it is still improvable, es- pecially in medical patients at risk.Consequently, hospitalwide strategies for systematic risk factor assessment and implementation of practical tools to ensure appropriate use of prophylaxis in patients at VTE risk are mandatory.This information was complemented by the SWIVTER Registry [5].In 14 Swiss hospitals, 567 consecutive patients (306 medical, 261 surgical) with acute VTE and hospital stay <30 days prior to the VTE event were enrolled.Prophylaxis had been administered in 329 (58%) patients during the previous hospital stay.Among the medical patients, 146 (48%) had received prophylaxis, and among the surgical patients 183 (70%) had received prophylaxis (p<0.001).The indication for prophylaxis was present in 262 medical patients (86%) and in 217 (83%) surgical patients.Among the patients with an indication for prophylaxis, 135 of the medical patients (52%) and 165 of the surgical patients (76%) received prophylaxis (p<0.001).
Admission to the intensive care unit [odds ratio (OR) 3.28, 95% confidence interval (CI) In the frame of IMPART [7], we compared various tools aiming at improving the adequacy of thromboprophylaxis among hospitalised acutely ill medical patients.We randomly assigned medical services across Switzerland to a pocket digital assistant programme (PDA), pocket cards (PC), and no clinical decision support system (CDSS) as controls.In centres using an electronic chart, an e-alert system (eAlerts) was developed.After 4 months we compared post-CDSS with baseline thromboprophylaxis adequacy for the various CDSS and control groups.Overall, 1085 patients were included (395 controls, 196 PC, 168 PDA, 326 eAlerts), 651 pre-and 434 post-CDSS implementation: 472 (44%) presented a risk of VTE justifying thromboprophylaxis (32% pre, 61% post) and 556 (51%) received thromboprophylaxis (54% pre, 47% post).The overall adequacy of pre-and post-CDSS implementation was 56% and 51% for controls (P = 0.29), 67% and 45% for PC (P = 0.002), 66% and 65% for PDA (P = 0.99), 51% and 56% for eAlerts (P = 0.37) respectively, eAlerts limited over-prescription (56% pre, 31% post, P = 0.01).Hence, while pocket cards and handhelds did not improve thromboprophylaxis adequacy, eAlerts had a modest effect, particularly in reducing overprescription.This effect only partially contributes to improvement of patient safety, and more work is needed towards institution-tailored tools.
As a follow-up study ESTIMATE was set up to prospectively validate the Geneva Risk Assessment Model (RAM) [14] through evaluation of the relationship between the combined rate of fatal and non-fatal symptomatic VTE (primary endpoint) and bleeding events at 90 days after hospital admission on the one hand, and the calculated risk score provided by the Geneva RAM at hospital admission on the other.The study will include at least 1000 patients, a goal that is about to be reached.Because a substantial proportion of venous thromboembolic events do occur after hospital discharge as initially reported in a large retrospective study from Geneva University Hospital [15], extended prophylaxis has been recommended in high-risk patients undergoing major orthopaedic surgery or major cancer surgery [2].In ESSENTIAL [8] we prospectively investigated thromboprophylaxis in 1046 consecutive patients undergoing major orthopaedic (70%) or major cancer (30%) surgery in 14 Swiss hospitals.Appropriate in-hospital prophylaxis was used in 1003 patients (96%).At discharge, 638 patients (61%) received prescription for extended pharmacological prophylaxis: 564 (77%) after orthopaedic surgery, and 74 (23%) after cancer surgery (p<0.001).Patients with knee replacement (94%), hip replacement (81%), major trauma (80%), and therapeutic arthroscopy (73%) had the highest prescription rates for extended VTE prophylaxis; the lowest rates were in patients undergoing major surgery for thoracic (7%), gastrointestinal (19%), and hepatobiliary (33%) cancer.Thus, approximately one quarter of the patients with major orthopaedic surgery and more than three quarters of the patients with major cancer surgery did not receive prescription for extended VTE prophylaxis.

Therapeutic aspects
The SWIVTER II and the OTIS-DVT registries [9][10][11]  Even though one might argue that many of the observations made and conclusions reached are far from original, the studies and surveys performed over a 6-year period by a multidisciplinary group of physicians across Switzerland point to insufficient awareness of venous thromboembolic disease, underestimation of its burden and inconsistent application of international consensus statement guidelines regarding prophylaxis [2] and treatment [15] adopted by the Swiss Expert Group [12].Consequently, implementation tools to improve compliance with current recommendations have been or are still being studied.It is worth noting that the network around this initiative fostered interest in and awareness of VTE in the participating university and regional hospitals and, anecdotally, also produced slide kits to disseminate the new knowledge in CME forums.-Acutely ill hospitalised at-risk medical patients are given thromboprophylaxis in only 61% of cases.
-In patients diagnosed with acute VTE who had been hospitalised within 30 days prior to the event, 70% of surgical patients but only 48% of medical patients had been given thromboprophylaxis during hospital stay; in cancer patients, the figure was as low as 60%.
-In high-risk patients undergoing major orthopaedic surgery or major cancer surgery, extended thromboprophylaxis was given in only 77% or 23% of the cases respectively.
-Long-term anticoagulant treatment was planned in less than half of cancer patients with VTE.
-There is considerable inconsistency in the prescribed duration of anticoagulant treatment in outpatients diagnosed with acute DVT.
-Mechanical compression as adjunctive treatment of symptomatic proximal DVT is prescribed for at least two years in only 24% of patients.

Funding / potential competing
interests: The SAMEX initiative was funded by unrestricted grants from Sanofi-Aventis (Suisse) SA.The ESTIMATE study has received unrestricted additional support from the International Society on Thrombosis and Haemostasis (ISTH) 2007 Presidential Fund.

Table 1 :
Studies conducted in the frame of the SAMEX initiative on VTE in Switzerland.
ESTIMATEProspective evaluation of a risk assessment model for predicting the need for thromboprophylaxis in acutely ill hospitalised medical patients.Study completed ESSENTIAL Assessment of extended thromboprophylaxis in patients undergoing major orthopaedic or major cancer surgery.Thromb.Haemost.2009; 102:56-61 OTIS-DVT Evaluation of practice patterns for the outpatient treatment of DVT and of planned duration of anticoagulant treatment.Thromb.Res.2011;127:406-10 Thromb.Haemost.2011;105:239-44 SWIVTER II Assessment of long-term anticoagulant prescription in cancer patients with VTE.Thromb.Haemost.2011;105:962-7 SWIVTER III Evaluation of practice patterns for primary and secondary prophylaxis in cancer patients with VTE.Study ongoing Review article: Current opinion Swiss Med Wkly.2011;141:w13241 Swiss Medical Weekly • PDF of the online version • www.smw.ch

Table 2 :
Main conclusions of the SAMEX initiative on VTE in Switzerland.