Weekly EBM Update: 12.7.2018 (Feat. Guest Star)

Welcome to the EBM Weekly Update!

This week we have an evidence update from the annual American Society of Hematology (ASH) meeting regarding the use of DOAC's for the treatment of cancer associated VTE. While in practice this had been done for sometime, this is one of the first trials (maybe the first?) showing superior efficacy with the use of a DOAC over LMWH. 

The second article review was selected and written by someone near and dear to many an IM residents’ heart- Dr. Daniel Green. Yes, we convinced this recent OHSU grad to make a cameo appearance from his Kaiser abode in sunny southern California and grace us with his EBM wisdom regarding the overzealous and potentially lethal use of oxygen therapy in nearly all hospitalized patients. We are forever grateful for his contribution! Thanks Dan ;) If any of you other current residents, alums, or faculty out there want to contribute to this effort, we’d love to have you!!

Apixaban, Dalteparin, in Active Cancer Associated Venous Thromboembolism, the ADAM VTE Trial (ASH 2018)

Historically, low molecular weight heparin (LMWH) was used for both prophylaxis and treatment of cancer associated DVT. Its superiority was demonstrated to coumadin in the CLOT trial (NEJM 2003), which demonstrated fewer episodes of venous thromboembolic disease (VTE) amongst patients receiving LMWH vs. oral anticoagulation with a coumadin derivative. However, with the advent of newer oral agents such as direct oral anticoagulants (DOAC’s), if LMWH remains superior remains to be seen. A non-inferiority trial published early this year in NEJM (2/2018) demonstrated that edoxaban was non-inferior to LMWH in patients with cancer associated DVT, however this was at the expense of increased bleeding, particularly amongst patients with GI malignancies. The authors of the above study evaluated the efficacy of 6 months of treatment with Apixaban (a DOAC) compared to dalteparin (LMWH) in the treatment of cancer associated VTE amongst 300 patients (287 included in primary analysis with colorectal, lung, pancreas, and breast the most prevalent cancer types). The authors found significantly fewer VTE’s in patients receiving apixaban compared to dalteparin (3.4% vs 14.1%, p-value: 0.0182). There was no difference in major bleeding between groups (0 and 2 patients, respectively), nor clinically relevant non-major bleeding.

Take Home: Among patients with cancer associated VTE, oral anticoagulation with apixaban appears to be a safe and effective treatment compared to LMWH. Further subgroup analysis is warranted to evaluate the safety of these agents amongst patients with GI malignancies.

Link to Conference Abstract Here

Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. (Lancet 4/2018) (By Contributor Dr. Daniel J. Green)

Background:  Most patients that are in the hospital will have a nasal cannula on whether they need it or not.  How do we know who needs supplemental oxygen therapy?

METHODS:  Systematic review and meta-analysis of randomized control trials in a variety of different databases comparing liberal versus conservative oxygen therapy in acutely ill adult inpatients (pts with chronic respiratory disease and a few other things like ECMO were excluded).  The outcome of interest was mortality (in hospital, 30-day, longest follow-up reported) and morbidity (hospital-acquired pneumonia, any infection, length of hospital stay, others).

Findings:  Twenty-five RCTs including ~16,000 patients with diseases such as sepsis, critical illness, stroke, trauma, myocardial infarction, cardiac arrest, and emergency surgery.  They compared conservative oxygen strategy (‘less is more’) verses liberal oxygen strategy (O2 sat median greater than 96%). More oxygen had a relative risk for in-hospital death of RR 1.2, 30-day mortality relative risk RR 1.14, all were statistically significant, and the I-square test for heterogeneity was low (favorable, meaning the studies were similar and easy to compare).

Critical Appraisal:  Broadly speaking, internally valid with high quality of evidence, low risk bias with low heterogeneity among numerous large randomized control trials.  Reasonably well generalized as the patient's included had a variety of different medical conditions.  Our veteran population has a high prevalence of chronic respiratory disease, I could not easily find what this term includes. If they excluded stable COPD, asthma patients etc., it would limit the generalization to our VA population.

 Take Home:  There is small but persistent risk of death, both short and long-term, from supplemental oxygen therapy titration to a saturation greater than ~96%.  Consider removing the nasal cannula to prevent death, prevent your patient from sitting in bed all day unnecessarily, and prevent dry nasal passages and discomfort.  But mostly death.

Link to Paper Here