Cost-Utility Analysis Comparing Direct Oral Anticoagulant and Low Molecular Weight Heparin Therapies for Secondary Prevention of Cancer-Associated Thrombosis.

BACKGROUND AND OBJECTIVE: Cancer patients are at elevated risk of cancer-associated thrombosis (CAT). Randomized controlled trials have found that direct oral anticoagulants (DOACs) are associated with fewer recurrent venous thromboembolism (VTE) events and an increased risk of bleeding than low molecular weight heparins (LMWHs) in CAT. With new clinical data available, this study aims to assess the comparative cost-effectiveness of DOACs and LMWHs over 6- and 60-month treatment durations from the US healthcare system and societal perspectives. METHODS: A Markov model for cancer patients eligible to receive rivaroxaban, edoxaban, apixaban, enoxaparin, or dalteparin was used to conduct a cost-utility analysis. Clinical scenarios were analyzed based on 6- and 60-month time horizons from the US healthcare system and societal perspectives. The main outcome was the incremental cost-effectiveness ratio (ICER), expressed as cost in US dollars per quality-adjusted life year (QALY). One-way and probabilistic sensitivity analyses were performed to evaluate the robustness of the results. RESULTS: DOACs were cost-saving and clinically superior to LMWHs and were associated with a cost change ranging from - $9134.66 to - $15,281.92 and incremental effectiveness of 0.43-1.25 QALYs among four clinical scenarios. The most influential model inputs for ICER were the utility associated with LMWH use and probabilities of non-VTE and non-bleeding related death. Probabilistic sensitivity analyses were consistent with the results. CONCLUSIONS: DOACs were found to dominate LMWHs, suggesting that DOACs may be a cost-effective alternative to LMWHs for CAT. This study can help inform decision-makers on the cost-effectiveness of anticoagulation strategies and help in the development of future practice recommendations for cancer patients.

Fondaparinux Sodium Compared With Low-Molecular-Weight Heparins for Perioperative Surgical Thromboprophylaxis: A Systematic Review and Meta-analysis.

Background Fondaparinux sodium has been compared with low-molecular-weight heparins ( LMWH ) in randomized controlled trials for perioperative surgical thromboprophylaxis. However, the results from these studies are inconsistent in terms of efficacy and safety to reach a clinical decision. The objective of this study was to systematically review the randomized controlled trials comparing the efficacy and safety of fondaparinux and LMWH for perioperative surgical thromboprophylaxis. Methods and Results Systematic search in various databases was done to identify randomized controlled trials comparing fondaparinux and LMWH published during the years 2000 to 2017. Outcomes of interest in this study included venous thromboembolism up to day 15, all-cause mortality up to day 90, major bleeding, and minor bleeding during the treatment period. Analyses were performed with the relative odds based on a random-effects model using Mantel-Haenszel statistics. Results were presented as odds ratios with their 95% CIs. The assessment of study quality was performed as per Cochrane collaboration. After screening 10 644 articles, 12 randomized controlled trials including 14 906 patients were included in the final analyses. Pooled analyses showed the odds of venous thromboembolism in the fondaparinux group were 0.49 times the odds in LMWH group ( OR =0.49 [0.38-0.64]). However, the odds of major bleeding in the fondaparinux group were 1.48 times the odds in the LMWH group ( OR =1.48 [1.15-1.90]). Conclusions Fondaparinux was associated with a superior efficacy in terms of reduction of venous thromboembolism in this meta-analysis. However, it was also associated with increased odds of major bleeding.

Impact of anticholinergic load of medications on the length of stay of cancer patients in hospice care.

OBJECTIVES: An important goal of hospice care is to relieve pain and suffering of terminal cancer patients. Anticholinergic medications are effective in the symptom palliation among terminal cancer patients. However, use of these medications has been associated with increased risk of side effects, which might lead to premature mortality. Short lengths of stay in hospice care leave patients with a higher level of unmet needs. The study was conducted to examine the effect of increasing anticholinergic load on the length of stay of cancer patients in hospice care in the USA. METHODS: The National Home and Hospice Care Survey 2007 was used as the data source. The Cox proportional hazards model was used to investigate the risk of death among users of moderate and high anticholinergic load compared with users of low anticholinergic load in presence of other prognostic factors. KEY FINDINGS: Cancer patients on a moderate anticholinergic load had a 12.7% lower hazard of death (P = 0.0244), while those on a high anticholinergic load had a 15.6% lower hazard of death (P = 0.0071) as compared with those patients on a low anticholinergic load. Among other prognostic factors, non-elderly age group, male gender, white race, metropolitan hospice agency, non-profit hospice agency, severe activities of daily living dependency and cognitive impairment were significantly associated with a higher probability of death. CONCLUSIONS: These results provide no evidence for increasing anticholinergic load increasing mortality in cancer patients using hospice care. Thus, high anticholinergic load might have conferred a protective effect on the patients because of better symptom control.

Prospective study of amphotericin B formulations in immunocompromised patients in 4 European countries.

BACKGROUND: Amphotericin B is a widely used broad-spectrum antifungal agent, despite being associated with significant adverse events, including nephrotoxicity. METHODS: The present prospective study collected data on outcomes for 418 adult patients treated consecutively with polyenes in hematology and oncology wards in 20 hospitals in Europe. RESULTS: Patients initially received amphotericin B deoxycholate (62% of patients), liposomal amphotericin B (27%), or other lipid formulations of amphotericin B (11%). Of the patients initially treated with amphotericin B deoxycholate, 36% had therapy switched to lipid formulations of amphotericin B, primarily because of increased serum creatinine levels (in 45.7% of patients) or other amphotericin B-attributable adverse events (in 41.3% of patients). Nephrotoxicity, which was defined as a > or = 50% increase in the serum creatinine level, developed in 57% of patients with normal kidney function at baseline. Predictors of nephrotoxicity included formulation type and duration of treatment. Compared with patients without nephrotoxicity, patients with nephrotoxicity had a higher mortality rate (24%), and their mean length of stay in the hospital was prolonged by 8.6 days. Slight increases in the serum creatinine level (i.e., > or = 50%) were associated with a significantly longer stay in the hospital. Severe nephrotoxicity (i.e., a > or = 200% increase in the serum creatinine level) was a significant predictor of death, as were severe underlying medical conditions and documented fungal infection. CONCLUSION: This prospective study confirmed that, in European hospitals, amphotericin B formulations have a major influence on the length of stay in the hospital and nephrotoxicity-associated mortality.