Digest 55: SURMOUNTing OSA

July 19, 2024 | By Nora Taranto

Welcome Back to The Curbsiders Digest!

In this issue, we cover nasal sprays to shorten URIs, new treatments for COPD, and more data on coffee!.  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. 

Yummy! 

If you or a friend are hungry for more, sign up here.

Menu 

Issue 55

07/19/2024

Appetizers (to whet your appetite) 

Palate Cleanser (aka the melon part of the meal) 

The Main Course

A Digestif or two

Appetizers

Brought to you hot off the stove, from a variety of specialties. Delivered in super tasty, bite-sized morsels. 
-Beth Garbitelli MD, Laura Glick MD; Alyssa Mancini MD; Jennifer DeSalvo MD

• Daily coffee drinkers rejoice! According to a study in the Journal of Hypertension, regular coffee consumption does not lead to increased blood pressure, compared to no coffee consumption. In this Italian prospective cohort study, 1400 participants were stratified based on self-reported coffee consumption (none, 1-2 cups, or > 3 cups daily).  After adjusting for confounders, daily coffee consumers and non-consumers had similar changes in blood pressure, with similar rates of new-onset hypertension, over 10 years (based on in-office, at home, and through 24-h-ambulatory monitoring).  Heavy (>3 cups) consumers had a lower mean systolic blood pressure in office compared to those with lower/no consumption, but there were no significant differences noted on ambulatory or home readings. (LG)
• Dupilumab–a new kid on the COPD block? NEJM recently published results from a phase 3, double-blind, randomized trial where almost 1000 patients with COPD and a blood eosinophil count of >300 cells/uL were randomized to subcutaneous dupilumab – a monoclonal antibody targeting drivers of type 2 inflammation – or placebo every 2 weeks. The annualized rate of moderate or severe exacerbations was 0.86 with dupilumab and 1.30 with placebo (rate ratio 0.66; 95% CI 0.54-0.82). The increase in prebronchodilator FEV₁ from baseline to weeks 12 and 52 was significantly higher with dupilumab. The incidence of adverse events was similar in the two groups. (AM) 
• Is it time to rethink statin eligibility? JAMA recently published a cross-sectional study of 3,785 adults aged 40-75 years without known cardiovascular disease, comparing 10-year risk estimates for atherosclerotic cardiovascular disease (ASCVD) for primary prevention statin therapy using the 2013 pooled cohort equations (PCEs) and the 2023 Predicting Risk of Cardiovascular Disease Events (PREVENT) equations, which removed race and added renal function and statin use. The mean 10-year ASCVD risk was significantly lower using PREVENT (4%) compared to PCE (8%) across all age, sex, and racial subgroups. Utilization of PREVENT may reduce the number of patients eligible for primary prevention statin therapy. (JD) 
• Test From Home for HCV. Hepatitis C Virus (HCV) infection is a major issue across the globe. Of the 50 million people with HCV, only about 36% have been officially diagnosed. The World Health Organization (WHO) just assessed and prequalified the first hepatitis C self-test, which can dramatically expand access for diagnosis, especially for those in low or middle income countries. An earlier version of the test was initially prequalified in 2017 for professional use (prequalification is a process from WHO to evaluate new advances in diagnostics, as a means to facilitate safety and accessibility of new technologies), with the WHO now prequalifying an extension of the test that can be performed by patients themselves. (BG)
• Shortening the Common Cold.  A new, intriguing study from The Lancet evaluated nasal spray use and length of self-reported acute upper respiratory infections (URI). In this open-label study, >13,000 participants were randomized to usual care (e.g. brief advice about cold symptoms), gel-based nasal spray, saline nasal spray, or a website with behavioral content promoting physical activity and stress management. Eligible participants had either frequent URIs (>3 yearly) or >1 risk factor for adverse outcomes (e.g. immunocompromise, asthma, lung disease, diabetes, obesity, age >65). Usual care patients were asked not to use OTC nasal sprays.  Patients in the nasal spray groups reported fewer days of illness compared to the usual care and website intervention groups, by ~2 days. (BG)

Palate Cleanser

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

Substantial disparities in medical knowledge, health outcomes, healthcare navigation, and health policies exist within women’s health, as highlighted by the National Academy of Medicine during their annual symposium last year. JAMA Internal Medicine published several editorials, including “Understanding and improving women’s health – from cells to society” and “Science and sex – a bold agenda for women’s health,” calling for increased female participation in research, especially pregnant and lactating women, and including sex as a biological variable in research to ensure that studies adequately include both sexes (thereby enabling better understanding of sex-based genetic differences in physiology and treatment). They also emphasize that disparities in research knowledge and lack of representation increase further when race and ethnicity are considered, and need addressing. The authors suggest featuring women’s health topics in medical education curricula to advance knowledge of future researchers, clinicians, policymakers, and leaders to “scale effective models and foster innovation along the continuum from cells to society… this investment, long overdue, will yield dividends for the health of more than half of the world’s population.” 

– Jennifer DeSalvo MD

The Main Course

Cyrus Askin, MD
Internal, Pulmonary & Critical Care Medicine

GLP-1 Agonism: Another way to SURMOUNT-OSA?
Obstructive Sleep Apnea (OSA) affects nearly 1 billion patients worldwide, and patients with OSA are at increased risk of developing atrial fibrillation, hypertension and stroke, as well as other conditions–many of which increase mortality. For many patients, OSA is relatively easy to treat…on paper.  Positive airway pressure (PAP) at night (via CPAP, APAP or Bi-Level devices) is often enough to improve a patient’s apnea-hypopnea index (AHI) and raise nocturnal oxygen saturations to acceptable levels. However, adherence and consistency are major issues with PAP therapy. Historically, other treatments such as surgical interventions and oral appliances have also had their own limitations. 

Now, enter GLP-1 agonists – specifically, Tirzepatide, a dual GIP/GLP-1 receptor agonist and a drug gaining popularity as an effective weapon to treat diabetes and obesity. Given that excess adiposity is a major risk factor for the onset and progression of OSA, it stands to reason that an effective weight loss agent might be a useful treatment for OSA. 

Breaking it Down 
SURMOUNT-OSA represents a pair of multi-center, international trials that randomized patients with moderate-to-severe OSA to tirzepatide or placebo for 52 weeks. Each study included approximately 230 non-diabetic adults with moderate-to-severe OSA by AHI and obesity (BMI >30). The first trial enrolled patients who were not on PAP, and the second trial enrolled patients already using PAP (with plans to continue it during the study). All patients in the control and treatment groups were instructed to maintain a 500 kcal/day deficit and to complete >150 minutes of exercise weekly.  The primary endpoint was change in apnea-hypopnea index (AHI) from baseline, with key secondary endpoints including reduction of > 50% in AHI events at 52 weeks, change in systolic blood pressure, and body weight. There was a decrease in AHI of nearly 25 events/hour with tirzepatide in Trial 1 and nearly 30 events/hour in Trial 2, compared to a drop in AHI of about 5 events/hour for both placebo arms. Body weight dropped ~20% with tirzepatide, compared to negligible changes with placebo. Sleep-related patient-reported outcomes also improved more with tirzepatide than with placebo. GI side effects were more prevalent with tirzepatide than with placebo, which is consistent with prior studies looking at GLP-1 agonists. 

What does it Mean?
SURMOUNT-OSA provides objective data demonstrating clinically meaningful improvements in AHI, body weight and sleep quality with tirzepatide compared to placebo. It is, of course, difficult to disentangle the effect of the drug on obesity and on OSA itself, with apparent benefits on both weight loss and OSA metrics. The study design – specifically the inclusion of international populations, the inclusion of those both on and not on PAP, and limits placed on male enrollment – improve its generalizability.  It is, however, important to remember that this study did not look at the effect of tirzepatide in non-obese patients with OSA, nor at whether patients on PAP therapy treated with tirzepatide could come off PAP with ongoing resolution of symptoms and AHI. Follow-up studies should be considered to address both these questions. Overall, this study focused on the population with obesity and OSA, with compelling results to support the use of tirzepatide in this population–in particular, in patients with obesity and OSA who are opposed to PAP therapy. These patients are historically undertreated and might now achieve a lower AHI and a lower BMI without ever having to put a PCPAP mask on.

Read The Trial HERE!

Digestifs

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

Consolidate your learning with a Quiz!  

This week on The Curbsiders: Just in time for your (and your patients’) summer adventures, we have Episode #449, Travel Medicine with Dr. Boghuma Titanji. This episode is packed with pearls about yellow fever, traveler’s diarrhea, malaria, and more! 

Comments for the Chef

We want to hear from you!

Please share your feedback and ideas in this Survey!

Thanks so much for joining us this week.

Until next time, keep that brain hole digesting! 

The Curbsiders Digest

Issue 55

Editor in Chief: Nora Taranto MD

Banner: Kate Grant  MBChB, DipGUMed

Disclosures:
Jennifer DeSalvo,  Alyssa Mancini, Laura Glick, Beth Garbitelli, and Nora Taranto report no disclosures.

Cyrus Askin reports no disclosures. 

Kate Grant reports no disclosures. 

PATREON is LIVE!

Sound Smart on Rounds with Kashlak Admitting Privileges.

Short 20-30 minute High-Yield Bonus Episodes (audio and video) covering topics such as:

-Hypertension

-Blood Pressure

-Chronic Kidney Disease

-And MUCH MORE!

Plus, AD FREE full episodes, access to Kashlak Vault (400+ show notes, infographics, scripts and more!) exclusive Merch and access to the Kashlak Community via Discord, an online forum where you connect with The Curbsiders team and other top-tier Members. Matt and Paul check in regularly and answer questions on medicine and more. Whether you are an Attending or a Resident, we can help you LEVEL UP your Knowledge for Rounds. Get Smart Now!