Sep 27, 2019


The story

On wards you often cross your fingers and hope for the best, but in clinic you want meds to conform to expectations. Here's how dapagliflozin surprised in heart failure with reduced ejection fraction (HFrEF).

The background

Results from 2015's EMPA-REG OUTCOME trial were as notable for how quickly study drug empagliflozin worked as for the magnitude of observed benefits. The sodium–glucose cotransporter 2 inhibitor (SGLT2i) reduced incident heart failure and heart failure hospitalizations within months of treatment initiation but had minimal impact on vascular events like myocardial infarction or stroke. Suspicion grew that effects were not related to hemoglobin A1C control – modest across the SGLT2i drug class – but tied to direct action in congestive heart failure.

The study

HFrEF patients with and without diabetes saw similarly improved outcomes with SGLT2i dapagliflozin in the 4,700-patient DAPA-HF trial. Treatment patients were 26% less likely to have worsening heart failure or CV-related death compared to placebo (16% vs 21%) after median follow-up of 18 months. A secondary outcome of decreased all-cause mortality was also positive. Hypoglycemia and hypovolemia were uncommon, and benefits appeared additive to other heart failure therapies.

The takeaway

SGLT2i’s are as much heart failure as diabetic meds and could quickly become a mainstay in HFrEF management. Expect further scrutiny of the still unknown cardiac mechanism of action.

Say it on rounds

When you're allergic to progress notes

Our condolences. But those with life-threatening peanut allergies are watching the literature on desensitization closely. A phase 2 trial of oral immunotherapy (OIT), in which patients are given escalating doses of peanut protein, found that most treatment patients were able to achieve 'sustained unresponsiveness' to peanut allergens over the 3-year study period. Known for causing GI and skin symptoms, OIT became more tolerable with time on treatment, though many patients regained peanut sensitivity when OIT was stopped.  

When your samples vanish in the tube system

You know better than to assume things work. A study of fresh frozen plasma (FFP) use in patients with cirrhosis and coagulopathy found that while FFP corrected INR and aPTT, it did little to correct thrombin generation, a more reliable metric for appropriate coagulation balance. Use of FFP actually decreased thrombin generation in about one-third of patients. The authors suggest transfusing platelets or fibrinogen for cirrhosis patients, and to consider PCC in severe bleeding. 
J Hepatol

When your plasma is at least 70% Diet Coke

A mammoth cohort study of 450,000 Europeans linked self-reported diet soda consumption to increased all-cause mortality over 16-year follow-up. Consumption of 2+ glasses of artificially sweetened beverages per day had a stronger association with mortality (HR 1.26) than total soft drink or sugar-sweetened soft drink consumption and was tied to an increased risk of death from circulatory disease (HR 1.5). Associations can be fluky across such a large data set, so look for more research before you toss your home supply. 
JAMA Int Med

Brush up

COPD diagnosis

All you need to diagnose chronic obstructive pulmonary disease is an FEV1/FVC ratio of < 0.7. But a few early work up steps can tell you much more. Early phenotyping with CT chest can measure extent of emphysema (think pink puffers) and luminal narrowing and wall thickening characteristic of bronchitis (blue bloaters). Both inform risk of lung cancer and circulatory disease. Check resting O2 saturation to determine need for supplemental oxygen and consider physiological testing (e.g. 6-minute walk test) for patients who report dyspnea on exertion. 

What's the evidence

For lab-guided treatment in COPD? Make sure to measure 2 labs in your early work up: alpha1-antitrypsin to rule out genetic disease (responsive to enzyme supplementation) and blood eosinophil counts. A 2016 patient-level meta-analysis of 11,000 COPD patients across 10 trials found that those with blood eosinophil counts of < 2% responded poorly to inhaled glucocorticoids and had an increased risk of pneumonia following inhaled glucocorticoid treatment.

What your ED friends are talking about

Copy forward starts as a survival mechanism and becomes a way of life: a study of ED residents found that physical exam and ROS findings were way over-documented in the EMR when compared to real life observation.

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