Prophylaxis In Ambulatory Patients Research Articles

Comparison of Khorana Vs. Onkotev Predictive Score to Individualize Anticoagulant Prophylaxis in Ambulatory Patients with Cancer

Background: The current guidelines [ J Clin Oncol. 2020;38(5):496] recommend using the risk assessment model (RAM) Khorana score ≥2 [ Blood. 2008;111(10):4902-4907] for primary anticoagulant prophylaxis (PP) of venous thromboembolism (VTE) in patients treated for cancer in an outpatient setting. Recently, a novel RAM, the ONKOTEV score [ JAMA Network Open 2023;6(2):e230010] has been prospectively externally validated with good predictive performance. Like all other established RAMs, the Khorana Score and ONKOTEV models aim to assess the incidence of VTE accurately but do not integrate the expected benefits and potential harms of treatment to determine the clinical utility of the competing management alternatives. We set out to compare the clinical utility of the Khorana Score vs. the ONKOTEV predictive model to guide the PP of VTE in patients receiving anticancer treatment. Methods: We used the ONKOTEV validation dataset (n=425). The ONKOTEV score included the Khorana Score (dichotomized as Khorana score >2 vs. ≤ 2) and three readily available clinical information (also dichotomized): history of previous VTE, the presence of metastatic disease, and clinical or radiological assessment of vascular or lymphatic compression by tumor. After assessing the models' performance (discrimination, calibration), we applied a generalized decision curve analysis (gDCA) to integrate the effects of treatments with the models' predictive accuracy. This, in turn, allowed us to develop individualized recommendations for using PP for VTE in patients receiving anticancer treatment. We calculated net benefits (NB) to compare three management strategies: don't provide any treatment vs. administer prophylaxis to all patients receiving anticancer treatment for VTE vs. use the Khorana or ONKOTEV model to guide PP of VTE. According to gDCA, the best treatment is the one with the highest NB. We obtained data on treatment effects from the meta-analysis of published randomized trials comparing direct oral anticoagulants (DOAC) and low-molecular-weight heparins (LMWH) vs. placebo [ Annals of Palliative Medicine. 2020;9(5):2970]. We estimated that DOAC reduced the risk of VTE by 57% [relative risk reduction (RRR) =0.57 (95%CI: 0.13 to 0.79)] and LMWH by 48% [RRR=0.48 (95%CI: 0.42 to 0.66)]. We assessed the major bleeding rate on DOAC as 0.01 (95%CI: 0.006 to 0.04) and 0.02 (95%CI: 0.01 to 0.03) for LMWH. Results: Both RAMs had a satisfactory performance. Harell's C discrimination statistics was 0.71 for ONKOTEV and 0.66 for Khorana Score with good calibration properties (with intercept and the slope not statistically significantly different from 0 and 1, respectively). Fig 1A shows the results based on the default assumptions: if the patient values avoiding the morbidity of VTE 1.6 to 5 times more (0.2<RV<0.6) than the major bleeding, then offering DOAC to all patients receiving PP for VTE represents the most optimal management strategy. When the patients would rather avoid the consequences of the major bleeding by >2.5x more than the morbidity of VTE, using the ONKOTEV model to guide the administration of DOAC represents the best treatment strategy. If we assume that RRR ≤ 0.2, relying on the ONKOTEV model to guide the use of DOAC becomes the most optimal approach to PP of VTE in patients receiving anticancer treatment (Fig 1B). Conclusion: ONKOTEV model is superior to Khorana Score in guiding individualized PP for VTE in ambulatory patients with cancer. It is particularly helpful when the patient values avoiding major bleeding more than the morbidity of VTE. Our analysis provides new recommendations for PP of VTE receiving outpatient treatment for cancer, calling for updating the current guidelines for PP of VTE in this setting.

Real world data for venous thromboembolisms (VTEs) in patients with active cancer: Thromboprophylaxis pooled analysis from GMaT and ACT4CAT studies.

6637 Background: Venous Thromboembolisms (VTEs) lead to many negative consequences for patients with active cancer and are reported up to 20%. They affect anticancer treatment plan, increase morbidity, mortality, economic burden, and escalate psychological drain. Current guidelines recommend pharmacologic prophylaxis for thrombosis in ambulatory cancer patients with Khorana score ≥2. Methods: GMaT and ACT4CAT are prospective observational phase IV studies conducted by HeSMO in Greece. The aim was to record the clinical practice for ambulatory patients with active cancer who received thromboprophylaxis and enrolled after signing informed consent. Studies were approved by the bioethics committee. Results: 1157 patients from 26 oncology clinics enrolled who received thromboprophylaxis. Tumor types: gastrointestinal 38.5%, lung 24.8%, urological 12.2%, gynecological 6.9%, breast 6.1% and others 11.5%. Treatment lines: 1st 62.5%, 2nd 15.1%, 3rd 4%, adjuvant 9.7% and neoadjuvant 5.9%. Age ≥65 in 55.2%, BMI ≥30 in 17.8% and males 59.9%. High-Risk for Thrombosis Agents (HRTAs) received 82.3%: platinum agents (52.9%), antimetabolites (49.0%) and immunotherapy (10.2%). Notably, 52.7% of anticancer agents had potential drug-drug interactions (DDIs) with Direct Oral Anticoagulants (DOACs). High thrombotic risk factors presented in table. Thromboprophylaxis duration was 5.1±3.3 months with: tinzaparin 91.2%, fondaparinux 4.6%, bemiparin 2.3%, enoxaparin 1.2%, rivaroxaban 0.4% and apixaban 0.3%. Intermediate thromboprophylaxis doses of Low Molecular Weight Heparins (LMWHs) received 62% of patients; 50% in adjuvant setting & 72.6% in metastatic. 32 thrombotic events reported (efficacy: 97.2%, 95%CI: 96.3-98.2%) and 26 grade 1 or minor bleedings (2.2%, 95%CI:1.4-3.1%). Patients receiving intermediate doses of LMWHs had less risk for thrombosis (p=0.0308). Conclusions: VTEs prophylaxis in ambulatory patients with active cancer was found safe and effective. Apart from Khorana score, metastasis, HRTAs and DDIs seem to affect clinical decision for thromboprophylaxis mainly with LMWHs and often using intermediate doses irrelevant of clinical setting. Cancer Associated Thrombosis (CAT) is not negligible risk for patients and oncologists appeared to be aware about this. Clinical trial information: NCT03292107 , NCT03909399 . [Table: see text]

VTE prophylaxis in ambulatory patients with lower limb immobilization: A retrospective audit

VTE prophylaxis in ambulatory patients with lower limb immobilization: A retrospective audit

Thromboprophylaxis for ambulatory surgery: Results from a prospective national cohort

BackgroundVenous thromboembolism (VTE) prophylaxis is not always part of the usual care of ambulatory surgery patients, and few guidelines are available. ObjectivesTo collect data on the application of VTE prophylaxis in ambulatory patients. DesignThe OPERA study is a large national survey performed in 221 healthcare facilities. PatientsAmong patients, 2174 who underwent one of ten selected procedures over two pre-defined days of investigation. Main outcome measuresAssessment and management of the postoperative VTE risk. ResultsThe postoperative VTE risk was assessed as nil (4.1% of the physicians), low (74%) or moderate (20%). This risk was assessed as lower (71%) in ambulatory surgery as compared to conventional surgery. In most centres (94%), a personal patient history of VTE was recorded preoperatively, and in 72% a prophylaxis protocol was systematically applied but only 40% of the responding centres had a written protocol for VTE prophylaxis. The postoperative period (discharge at home) was covered by a VTE protocol for 75% of the centres, with VTE prophylaxis starting postoperatively in 21% of the patients. In these patients, different treatments were applied: below-knee compression stockings (25%); thigh-length compression stockings (21%); intermittent pneumatic compression in the recovery room (1.2%); unfractionated heparin (2.0%); low molecular weight heparins (65%); vitamin K antagonists (0.5%); other treatments, including direct oral anticoagulants (0.5%). ConclusionThese data underline the need for a better assessment of the VTE risk in ambulatory patients and new studies either with conventional or new agents to be able to build guidelines in this new setting.

Primary prophylaxis of VTE in cancer outpatients

Cancer patients have a significantly higher risk of developing venous thromboembolism (VTE) compared to non-cancer patients and several studies suggest that VTE risk among ambulatory cancer patients varies widely. Recently, predictive models capable of risk-stratifying a broad range of ambulatory cancer outpatients have been developed and validated; using the Khorana model a score of 2 is associated with an intermediate-high risk for VTE. However, the use of VTE prophylaxis in ambulatory patients who have cancer remains controversial. Even if important randomized clinical trials showed decreased rates of VTE events among patients who were receiving chemotherapy, the effect of prophylaxis on morbidity, mortality, and costs has not been rigorously studied. Outpatients with active cancer should be assessed for thrombosis risk and although most do not routinely require thromboprophylaxis, it should be considered for high risk patients.

Low molecular weight heparin (LMWH) for primary thrombo-prophylaxis in patients with solid malignancies – systematic review and meta-analysis

Background. Patients receiving chemotherapy for cancer are at increased risk for venous thromboembolism (VTE). We performed a meta-analysis of all randomized controlled trials (RCTs) which evaluated low molecular weight heparin (LMWH) as primary prophylaxis in ambulatory patients with solid malignancies.Methods. A comprehensive search was conducted until October 2013. Primary outcome was symptomatic VTE. Secondary outcomes were pulmonary embolism (PE), any VTE, deep vein thrombosis (DVT), mortality and adverse events.Results. Eleven trials met the inclusion criteria, and evaluated a total of 6942 patients. Primary prophylaxis with LMWH reduced symptomatic VTE (RR 0.46, 95% CI 0.32–0.67) and the rate of PE (RR 0.49, 95% CI 0.29–0.84). In the subgroup analysis of VTE in patients with lung and pancreatic cancers LMWH further reduced VTE [RR 0.42 (95% CI 0.25–0.71); RR 0.31 (95% CI 0.18–0.55), respectively]. Meta-analysis of six trials which reported survival outcomes revealed no statistically significant benefit for LMWH in one-year mortality rates (RR 0.93, 95% CI 0.83–1.04). There was no significant increase in major bleeding events (RR 1.28, 95% CI 0.84–1.95).Conclusions. LMWH reduces the incidence of symptomatic VTE and PE in patients receiving chemotherapy for cancer, with no apparent increase in major bleeding. The benefit is most apparent in pancreatic cancer and also lung cancer. VTE prophylaxis should be considered for these specific populations.

Thromboprophylaxis Guidelines in Cancer with a Primary Focus on Ambulatory Patients Receiving Chemotherapy: A Review from the Southern Network on Adverse Reactions (SONAR)

Patients with cancer are at increased risk for venous thromboembolism (VTE). Factors related to cancer type, site, stage, duration, and extent of disease contribute to the oncology patient's risk of VTE. Patient-specific factors such as history of prior VTE and comorbidity are also contributory. The role of treatment-related factors, including chemotherapy regimen, has been a focus of recent investigation because most cases of VTE in the oncology setting occur in ambulatory patients. Thus, an emerging area of clinical research is primary VTE prophylaxis in the ambulatory cancer setting. Clinical guidelines currently recommend primary thromboprophylaxis in cancer patients who are undergoing surgery, who are hospitalized, and who are in a specific subset of high-risk ambulatory cancer patients. Validated risk stratification tools are essential for identification of patients who are at high risk of thrombosis. Emerging data from recently published clinical trials, as well as ongoing studies, are likely to advance our understanding of the potential utility of antithrombotic agents for primary prophylaxis in ambulatory patients with cancer and may influence future clinical guideline recommendations.

Management of venous thromboembolism in patients with cancer.

Patients with cancer are at increased risk of venous thromboembolism (VTE). In these patients VTE is associated with substantial morbidity and complicates the clinical management of cancer. Emerging research indicates a probable detrimental effect of VTE on cancer survival. Although VTE may develop at any stage of cancer disease, the risk of VTE is particularly high in association with three clinical settings including surgery for cancer, use of a central vein catheter (CVC) and chemotherapy. Guidelines recommend post-operative prophylaxis (for at least 7-10 days) for patients undergoing elective cancer surgery. A prolonged prophylaxis (for upto four post-operative weeks) is recommended in cancer patients at high risk for VTE. The role of antithrombotic prophylaxis in the prevention of CVC-related thrombosis remains controversial. The PROTECHT study has recently evaluated the benefit of antithrombotic prophylaxis in cancer patients receiving chemotherapy, showing a statistically significant 50% relative risk reduction in symptomatic thromboembolic events. The international guidelines currently agree in non-recommending routine prophylaxis in ambulatory patients who receive anticancer chemotherapy but suggest an individual risk-based evaluation. To better identify cancer patients at high risk for VTE, simple predictive models have been validated. Further intervention studies are currently on-going to explore the benefit of antithrombotic prophylaxis in individual high-risk groups of patients. The long-term treatment of cancer-related VTE is based on therapeutic doses of LMWH in preference to warfarin. The optimal duration of antithrombotic treatment in cancer patients remains to be fully defined.

Prevention of Thrombosis in Ambulatory Patients With Cancer

Cancer patients with solid tumors or hematologic malignancies receive most of their cancer treatment as outpatients. Thromboembolism, when it occurs, complicates the clinical care of these patients because of the associated morbidity and the need for anticoagulant treatment. It would seem that prevention of venous thromboembolism in these patients would be worthwhile. However, to date there are relatively few trials of anticoagulant prophylaxis in ambulatory patients with cancer and it is not possible to recommend prophylaxis for most patients. Research is needed to better define a population at high enough risk to warrant pharmacologic prophylaxis and to develop new antithrombotic agents for this indication.

Antiarrhythmic prophylaxis in ambulatory patients with coronary heart disease

Antiarrhythmic prophylaxis in ambulatory patients with coronary heart disease