Prophylaxis for Thromboembolic Disease with Low Molecular Weight Heparins in Adult Patients in Home Care

PICHON RIVIERE, A.; AUGUSTOVSKI, F.; GARCIA MARTI, S.; GLUJOVSKY, D.; ALCARAZ, A.; LOPEZ, A.; BARDACH, A.; CIAPPONI, A; URTASUN, M

Documento de Evaluación de tecnologías Sanitarias

IECS

Año: 2013 p. 1 - 30

1668-2793

Venous Thromboembolic Disease (VTED) includes venous thrombosis and pulmonary thromboembolism (PE), its main complication. VTE main risk factors include having presented previous episodes of VTE, advanced age, exposure to surgery, trauma, hospitalization, neoplasm and paresis of the extremities. Among surgeries, those who entail higher risk are the ones of hip or knee. In Europe, the annual incidence is 160 cases of DVT every 100,000 inhabitants, 50 of them develop fatal PE. The highest mortality presents during the first hours of evolution, therefore, prophylaxis reduces it dramatically. Heparin is one of the main drugs used for preventing VTE. Initially standard or non-fractionated (NFH) was used until two decades ago when low molecular weight heparins (LMWH) appeared with higher bioavailability, faster clearance, simple administration and less need for control lab tests, although more expensive.TechnologyLMWH are heterogeneous substances obtained from the traditional non fractionated heparin by different chemical or enzymatic depolymerization methods thus obtaining structurally different products and with different anticoagulating/antithrombotic capabilities and different adverse effect profile.PurposeTo assess the available evidence on the efficacy, safety and coverage policy related aspects about the use of LMWH vs. NFH for the prevention of VET, DVT, PE in patients immobilized at home health care due to conditions such as cancer, orthopedic surgeries or advanced age.MethodsA bibliographic search was carried out on the main databases: DARE, NHS EED, on Internet general search engines, in health technology evaluation agencies and health sponsors. Priority was given to the inclusion of systematic reviews; controlled, randomized clinical trials (RCTs); health technology assessments and economic evaluations; clinical practice guidelines and coverage policies of other health systems.ResultsNo evidence comparing the use of LMWH vs. Sc NFH for patients immobilized or in home care was found. Evidence was found on the assessment of LMWH vs. comparators such as placebo or mechanical prophylactic methods for the subgroup of interest. Two systematic reviews, three randomized clinical trials (RCT), one observational prospective study of several case series, seven clinical practice guidelines, one expert consensus, two health technology evaluation reports and three health sponsor´s coverage policies were included.Patients who Underwent Orthopedic SurgeriesIn 2008, one systematic review on adults who underwent arthroscopy of the knee was published. It included four studies and a total of 527 patients. The methodological quality of the RCTs was variable. When comparing any kind of LMWH vs. Placebo, an Absolute Risk Reduction (ARR) of event occurrence of 6.4% and an OR of 0.14 (95%CI, 0.04-0.48) were reported in the LMWH group. Adverse events were more common in the intervention group (LMWH), being mild bleeding the most common one with a RR of 2.41 (95%CI, 1.08-5.36).Another 2000 RCT on the efficacy and safety of extended ambulatory prophylaxis after total hip replacement (THR) or total knee replacement (TKR) randomized 1,195 patients to one dose/day of Sc ardeparin (100IU/kg of weight) or placebo. No significant differences were observed in the incidence of thrombotic events or death.Another 2005 RCT assessed the effectiveness of the continuous passive motion exercise devices (CPM) after trauma. It included 227 patients randomized to therapy with CPM + LMWH vs. LMWH alone. The incidence of events in the LMWH was 2.5% vs. 3.6% (p<0.01) in the group that used CPM.Cancer PatientsOne 2012 systematic review on ambulatory cancer patients under chemotherapy treatment included nine RCTs on a total of 3,538 patients; it compared therapy with any oral or parenteral anticoagulation agent, mechanical devices or both vs. Inactive control. None of them evaluated NFH, Factor Xa direct inhibitors or mechanical interventions. LMWH vs. Inactive control significantly reduced the incidence of symptomatic DVT with a RR of 0.62 (95%CI, 0.41-0.93).Elderly PatientsOne 2011 RCT assessed the efficacy of the VTE prophylaxis in hospitalized patients over 70 years old. Three thousand two hundred and thirty nine patients were randomized to certoparin (LMWH) 3,000 IU/day or Sc NFH 5,000 IU three doses/day for 8 to 20 days. Certoparin and NFH were equally effective. There were no statistically significant differences as to major bleeding.The Clinical Practice Guideline published in 2012 by the ACCP (American College of Chest Physicians) on prevention in patients with orthopedic surgery recommend the use of LMWH, fondaparinux, apixaban, dabigatran, rivaroxaban, NFH at low doses or vitamin K antagonists (VKA) for 10 to 14 days or an intermittent pneumatic compression device (CPM) after the replacement. In case of higher risk of bleeding, a CPM or no prophylaxis is suggested. No drug prophylaxis is recommended in patients with isolated lesions in the lower limbs requiring immobilization or in those who underwent an arthroscopy of the knee with no previous history of VTE. In ambulatory cancer patients with no additional risk factors for VTE, the ACCP recommends not to use standard prophylaxis with LMWH or NFH. In elderly patients who are chronically immobilized at home or at an institution, the standard use of prophylactic therapy for thrombosis is not recommended.Coverage Policies: The main health sponsors cover the use of LMWH up to 30 or 35 days after total hip replacement, knee replacement or hip fracture. Its use is covered for two weeks after arthroscopy.ConclusionsNo evidence was found on the subcutaneous use of NFH in preventing DVT-PE in immobilized patients in home care, after an orthopedic surgery, cancer or elderly. New studies will be necessary to determine its use in this population.About the use of LMWH in preventing DVT-PE after orthopedic surgery, cancer or in the elderly, the studies found presented an adequate level of evidence which shows that LMWHs are as efficacious as intravenous NFH, they have a simpler follow up and administration but they have a slight increase in the incidence of bleeding and they are more expensive.The indication of LMWH is at the same level as the other anticoagulation agents in hip or knee replacement, being the alternative of choice in facture of the hip. In case of high risk of bleeding after a major orthopedic surgery, mechanical prophylaxis is recommended. In both cancer and elderly patients, unless there are no added risk factors, the use of anticoagulation prophylaxis is not recommended.