Digest #51: A Mid/Mad March Edition

March 22, 2024 | By

The Curbsiders Digest

Welcome Back to The Curbsiders Digest!

In this issue, we cover SELECTing patients for semaglutide, new treatments for food allergy,  guideline updates on albumin use, blood-based screening for colorectal cancer, and resolution of subclinical hypothyroidism. 
Effortlessly absorb important medical news, with our twice monthly newsletter featuring easily digestible analysis of the latest practice-changing articles, and of course…bad puns. 


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Issue 51


Appetizers (to whet your appetite) 

Palate Cleanser (aka the melon part of the meal) 

The Main Course

A Digestif or two


Brought to you hot off the stove, from a variety of specialties. Delivered in super tasty, bite-sized morsels. 
-Jennifer DeSalvo MD, Laura Glick MD, Hannah Smith MD

  • Cracking a hard nut with omalizumab? A multi-center, double-blind, placebo-controlled trial (OUtMATCH) just published in NEJM found that omalizumab, a monoclonal anti-IgE antibody, may reduce the risk of allergic reactions in individuals with multiple food allergies, including peanut. 177 participants (age 1 to 55)  allergic to peanuts and >2 other foods were randomized to receive omalizumab or placebo injections every 2-4 weeks for 16-20 weeks. Following this, 67% of patients in the omalizumab group were able to tolerate 600 mg or more of peanut protein, versus 7% with placebo (P<0.001).  Findings were similar for secondary endpoints, which included participants’ threshold reactivity to other common food allergens including milk, eggs, wheat, and tree nuts. The FDA subsequently approved omalizumab to reduce allergic reactions in adults/children >1 year old with IgE-mediated food allergies. (LG) 
  • Subclinical hypothyroidism may spontaneously normalize in older adults. A pooled data-analysis, recently published in JCEM, combined data from two randomized, double-blind, placebo-controlled trials (TRUST, IEMO 80-plus), and included patients over age 65 with subclinical hypothyroidism (an elevated TSH level with a normal FT4 level), not on thyroid replacement. The first cohort (pre-trial, screening population) included 2335 patients with one elevated TSH level and a repeat one year later–at which point, 61% experienced TSH normalization.  The second cohort (on-trial, placebo) included 361 patients with two abnormal TSH levels checked three months apart.  40% of these patients had normalization of their TSH after one year. TSH was more likely to normalize in patients who were female, younger, had smaller baseline TSH elevations, and had no thyroid peroxidase antibodies. (LG) 
  • Total Major Adverse Cardiovascular Events (MACE) with Bempedoic Acid. In the CLEAR randomized, placebo-controlled trial, 13,970 adults with or at high risk for cardiovascular disease with an elevated LDL and statin intolerance were randomized to treatment with bempedoic acid or placebo, with improvement in risk of MACE. This pre-specified analysis, just published in JAMA, assessed the total/cumulative incidence of events among high-risk patients.  Over 3.4 years of median follow-up, treatment with bempedoic acid was associated with a significant reduction in total incidence of MACE-4 events (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and coronary revascularization; HR 0.8, 95% CI 0.72-0.89, P <.001), with similar results for key secondary endpoints including myocardial infarction and coronary revascularization (but not stroke). Greater risk reduction was observed with increasing numbers of cardiovascular events, highlighting bempedoic acid’s benefits among those with high cardiovascular risk.  (JD) 
  • When to pull out al(l) the Albumin stops? New guidelines from the International Collaboration for Transfusion Medicine provide updated recommendations on the use of intravenous (IV) albumin. The panel ultimately makes only two conditional recommendations for intravenous albumin use, in (1) patients with cirrhosis and ascites undergoing large volume paracentesis (>5 liters) (very low certainty of evidence); and (2) patients with cirrhosis and spontaneous bacterial peritonitis (low certainty of evidence). Notably, these guidelines do not otherwise recommend albumin use in critically ill adult patients as first-line volume replacement, to increase serum albumin levels, in patients with cirrhosis and extra-peritoneal infections, in patients requiring diuretics or renal replacement therapy, or in patients undergoing cardiovascular surgery. (JD) 
  • A blood test to ECLIPSE Colonoscopies? In ECLIPSE, a study of a cell-free DNA (cfDNA), blood-based test for colorectal cancer (CRC) screening just published in NEJM, researchers assessed the performance characteristics of the cfDNA test, compared to colonoscopy screening. The cfDNA test (by Guardant Health) looks at DNA genomic alterations/fragmentation and methylation status and integrates detections into either a positive or negative test. Almost 8,000 participants at average risk for CRC underwent routine colonoscopy screening and cfDNA testing.  The cfDNA test had 83% sensitivity for the detection of CRC, 13% sensitivity for advanced precancerous lesions, and a 90% specificity for advanced neoplasia, with a specificity that inversely correlated with age. Given that not all patients are able or willing to undergo routine screening colonoscopy, this blood-based tool may ultimately be a useful screening modality–though questions remain about screening interval, integration with colonoscopy and stool testing, and cost. (HS) 

Palate Cleanser

The melon part. To get rid of the taste of those pesky apps.  And to fill your brain with some fun facts.

The Hospital is Bananas…  

Have you ever wondered about the seemingly never-ending stash of pale green and brown-spotted bananas gathering dust in the hospital physician lounges? As Dr. Teresa Samson writes in “When Life Gives You Hospital Bananas,” it’s easy to grab this snack-turned-meal when you’re running to see yet another new consult or return the next urgent page during your brief lunch break from seeing patients.  It’s also easy to forget them, after we’ve grabbed a banana and stuffed it in our pockets or backpacks, for later, when things settle down–a hope that often may not be realized.  But she notes that although the colors of these bananas can reflect our exhaustion and burnout from our workload, they may also fuel our hope for a minute more of a snack break–and more, calmer moments–the next day, and the day after that. Not to mention, with those squished, browner bananas, the amazing banana bread possibilities. 

– Jennifer DeSalvo MD 

The Main Course

Alyssa Mancini MD
Pulmonary & Critical Care Medicine

SELECTing Semaglutide:   

Reducing cardiovascular events in patients with overweight or obesity
The U.S. Food and Drug Administration (FDA) just approved a new indication for subcutaneous semaglutide – to reduce the risk of major cardiovascular events in adults with cardiovascular disease and overweight or obesity. This is the first weight loss medication to be approved for this indication in this patient population. 

Over the past few years, data have been building to support the benefit of semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, in improving weight and cardiovascular outcomes.  First, the STEP trials assessed the magnitude of weight loss in participants with overweight or obesity (with or without type 2 diabetes) who received semaglutide. Subsequently, STEP-HFpEF found that in participants with obesity and HFpEF, semaglutide reduced heart failure symptoms and physical limitations (see Digest #46 for more on STEP-HFpEF).  The SUSTAIN trials, including SUSTAIN-6, also revealed a lower rate of major adverse cardiovascular events in patients with type 2 diabetes with high cardiovascular risk who received semaglutide.  That brings us to SELECT, which assessed whether semaglutide could reduce cardiovascular risk associated with overweight and obesity in the absence of diabetes–and was the basis for the FDA approval above.

Breaking it Down
SELECT was a double-blind, randomized, placebo-controlled trial that was conducted in 41 countries. The trial enrolled >17,600 participants over age 45 (mean age 62 years, 72% male) who had preexisting cardiovascular disease and a BMI > 27 (mean BMI 33) without diabetes. More than 75% of participants had a previous myocardial infarction, and the use of guideline-based medical therapies for cardiovascular disease was well-balanced between groups.  Participants were randomly assigned 1:1 to receive once-weekly subcutaneous semaglutide 2.4 mg (after dose escalation) or placebo, in addition to standard-of-care medical treatment and lifestyle counseling.  Treatment with an open-label GLP-1 receptor agonist was initiated during the trial (a trial violation) in 36 semaglutide-arm patients and 121 placebo-arm patients.  Additionally, SGLT2 inhibitor therapy was initiated in 213 semaglutide-arm patients and 332 placebo-arm patients. 

Mean duration of exposure to semaglutide or placebo was 34 months over a mean follow-up of 40 months. As expected, mean change in body weight was significantly greater with semaglutide than with placebo (estimated treatment difference -8.51 percentage points, 95% CI -8.75 to -8.27).  The primary end point – a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke (i.e. major adverse cardiovascular events) – occurred in 6.5% of participants in the semaglutide group and 8.0% in the placebo group (HR 0.80, 95% CI 0.72-0.90, p<0.001)–with risk reduction independent of baseline BMI.  Serious adverse events were less frequent with semaglutide than with placebo, but adverse events (primarily gastrointestinal) causing permanent treatment discontinuation occurred in 16.6% of semaglutide-arm patients and 8.2% of placebo-arm patients (p<0.001). 

What Does it Mean?
In patients with preexisting cardiovascular disease and overweight or obesity, but without diabetes, subcutaneous semaglutide 2.4 mg weekly significantly reduced the risk of major adverse cardiovascular events. This effect is likely achieved through multiple interrelated pathways, including demonstrated improvement in cardiometabolic risk factors like blood pressure, glycemic control, lipid levels, and waist circumference.  It is important to remember that since this trial included participants with preexisting cardiovascular disease, it did not look at primary prevention–not to mention the limited diversity of the study population (only 28% women and 4% Black).  That said, ultimately, SELECT adds to the pharmacologic toolbox for risk mitigation in the population with CVD and overweight and obesity, and we anticipate that this new FDA approval will lead to greater uptake in this population…and, we hope, increased insurance coverage as well.

Read The SELECT Trial HERE!


Before you go….
we’ve got a few nibbles!

Consolidate your learning with a Quiz!  

This week on The Curbsiders: We have a phenomenal pericarditis/myocarditis primer this week, with Episode #431, featuring Dr. Vivek Kulkarni. Learn the physical exam findings to look for, the diagnostic tests and emergencies to call your cardiology colleagues about, and the basics of treatment. Very hearty!

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The Curbsiders Digest

Issue 51

Editor in Chief: Nora Taranto MD

Banner: Kate Grant  MBChB, DipGUMed

Jennifer DeSalvo,  Alyssa Mancini, Hannah Smith,  and Nora Taranto report no disclosures.

Kate Grant reports no disclosures


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Episode Credits

The Curbsiders Digest

Issue 51

Editor in Chief: Nora Taranto MD

Banner: Kate Grant  MBChB, DipGUMed

Jennifer DeSalvo, Alyssa Mancini, Hannah Smith, and Nora Taranto report no disclosures.

Kate Grant reports no disclosures.

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