Digest 71: The Overstuffed With Pearls Edition

November 22, 2025 | By Nora Taranto

Welcome Back to The Curbsiders Digest!

In this special Thanksgiving issue, we discuss rethinking beta blockers after acute MI, GI safety of GLP-1s, and more practice-changing insights and so much more! 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 71

11/21/2025

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 “Garbs” Gasperlin MD, Joshua Gilman MD, Alyssa Mancini MD

• GLP1s and risk of severe gastrointestinal events. The Annals of Internal Medicine recently published the results of a new-user active-comparator cohort study looking at the risk of severe gastrointestinal events (acute pancreatitis, biliary disease, bowel obstruction, gastroparesis, and severe constipation) in adults with type 2 diabetes initiating dulaglutide, semaglutide, or tirzepatide. There were over 65,000 matched pairs in the semaglutide vs. dulaglutide cohort with a HR of gastrointestinal events  of 0.96 (95% CI 0.87-1.06), over 20,000 in the tirzepatide vs. dulaglutide cohort (HR 0.96, 95% CI 0.77-1.20), and over 46,000 in the tirzepatide vs. semaglutide cohort (HR 1.07, 95% CI 0.90-1.26). Overall, these findings suggest that dulaglutide, semaglutide, and tirzepatide have similar gastrointestinal safety profiles in this patient population. (AM) 
• Discordance between cystatin C- and creatinine-based GFR and clinical outcomes. JAMA recently published the results of an individual participant-level meta-analysis looking at differences between cystatin C-based estimated glomerular filtration rate (eGFRcys) and creatinine-based estimated glomerular filtration rate (eGFRcr), and associations with mortality, cardiovascular events, and kidney failure. The study included over 821,000 participants from 23 outpatient cohorts in the Chronic Kidney Disease Prognosis Consortium (CKD-PC). 11% of participants in the outpatient setting and 35% in the inpatient setting had an eGFRcys at least 30% lower than eGFRcr. Characteristics associated with this large difference included older age, current smoking, heart failure, liver disease, COPD, peripheral arterial disease, and higher BMI. At a mean follow up of 11 years, having a larger eGFR difference (compared to having a smaller difference between cystatin- and creatinine-based measures) was associated with higher rates of all-cause mortality, cardiovascular mortality, atherosclerotic cardiovascular disease, heart failure, and kidney failure with replacement therapy. (AM) 
• DoxyPEP & Antimicrobial Resistance: Due to rising global rates of chlamydia, syphilis and gonorrhea, physicians have turned towards proactive prescribing of DoxyPEP (or Doxycycline Post-exposure Prophylaxis for Bacterial STI Prevention, check out more info via the CDC) for at-risk populations. Multiple studies have demonstrated reduced risk for sexually transmitted infections in men who have sex with men and other groups, especially with reduction of syphilis and chlamydia. Researchers from France recently published a study in Clinical Infectious Diseases reviewing antimicrobial resistance profiles among patients (identifying as men who have sex with men, on HIV PrEP) who were randomized to DoxyPEP or no PEP and were tested for gonorrhea and chlamydia (GC) every 3 months. GC-positive samples in the DoxyPEP arm showed increased resistance to tetracycline compared to the no-PEP arm. While isolates remained susceptible to ceftriaxone, researchers noted that DoxyPEP isolates demonstrated decreased susceptibility to cefixime. This review highlights the importance of STI screening for patients on prophylaxis. Further studies are needed to assess antimicrobial resistance risks with such an approach. (BG)
• Pros of the PSA? Prostate cancer screening has long been a controversial topic due to concerns about both overtreatment and the harms from invasive biopsy practices and aggressive surgery practices (though there have been a number of advances in diagnostics, treatment, and active surveillance approaches to minimize these risks over the last 30 years). Investigators from the European Randomized Study of Screening for Prostate Cancer just published 23-year follow-up results in NEJM that investigated long-term outcomes with PSA screening (every 2 – 7 years from ages 55 to ~70) in their cohort of over 162,000 men. As expected, prostate cancer diagnoses (and more early/low-risk diagnoses) occurred more frequently in the screening group. Prostate-cancer mortality was 13% lower in the screening group, with approximately 1 death prevented for every 456 men screened. (BG)
• Sip, sip, hooray – coffee lovers with atrial arrhythmias rejoice! Despite coffee’s reputation as a potential proarrhythmic agent, the DECAF trial recently published in JAMA explored the effect of caffeinated coffee consumption compared to abstinence on recurrent atrial fibrillation (AF) or atrial flutter (AFL). This prospective, open-label, multi-center clinical trial enrolled 200 patients with persistent AF or AFL with a history of AF following electrical cardioversion who currently or previously (within the past 5 years) consume caffeinated coffee. Patients were randomized 1:1 to regular caffeinated coffee consumption (≥1/day) vs coffee/caffeine abstinence for 6 months. Among the study participants (mean age 69, 71% male), patients who consumed caffeinated coffee had a lower rate of AF/AFL recurrence (47%) compared to those in the abstinence group (64%), translating to a 39% reduction in recurrence risk (HR 0.61; 95% CI, 0.42-0.89; P = .01). Cheers to evidence-based sipping! (JD) 

Palate Cleanser

The melon part. To get rid of the taste of those pesky apps.  And to fill your brain with some fun facts.
How do you decide whether the day calls for a business-casual ‘fit versus scrubs paired with your white coat? A recent systematic review published in BMJ reminds us that physician attire shapes patients’ perceptions of professionalism, trustworthiness, and communication–but that preferences shift with clinical settings, medical specialty and physician gender. In outpatient and primary care settings, several studies found that casual attire and white coats may enhance physician-patient communication. However, in the ED and OR, patients favored scrubs given their association with professionalism and preparedness. Additionally, patients had different perceptions of physician attire according to specialty, with preferences for white coats within ophthalmology, dermatology, and neurosurgery, while scrubs were preferred in gastroenterology and anesthesiology. Interestingly, gender-specific differences were also present, as male physicians were perceived as more professional donned in formal attire with white coats, whereas female physicians in similar dress were often misidentified as nurses or assistants. These findings indicate that patients’ perceptions are highly variable, implying that an evidence-based wardrobe titrated to the clinical environment (and personal preference) may be the newest, least controversial way to boost trust and patient satisfaction metrics. 

– Jennifer DeSalvo MD 

The Main Course

The Ever Changing Utility of Beta Blockers

Joshua Gilman MD

A History Lesson

Beta blockers (BB) have been a cornerstone of treatment for patients with acute coronary syndrome (ACS) and myocardial infarction (MI) for over 40 years. Large randomized control trials (RCTs)–including BHAT, NMSG, ISIS-1, MIAMI and CAPRICORN–showed a benefit in general mortality and cardiovascular (CV) mortality/morbidity with the use of post-MI BBs. The benefit of BBs in this setting is attributed to their ability to reduce myocardial oxygen demand, reduce adverse cardiac remodeling, and lower rates of ventricular arrhythmias. A landmark meta analysis in 1999 evaluated long-term BB therapy in 55,000 patients with ACS and showed a 23% long term relative risk reduction in mortality with BB use. Studies from this era subsequently clarified that patients with a reduced left ventricular ejection fraction (LVEF <40%) derive a particular benefit from BB therapy. This data, along with countless observational trials, has led the AHA/ACC to recommend long-term post-MI beta blocker use throughout multiple prior iterations of their guidelines, including the 2011 secondary prevention, the 2013 STEMI, the 2014 NSTEMI as well as their most recently updated 2023 chronic coronary disease (CCD) and 2025 acute coronary syndrome (ACS) guidelines.  

Updates in the Revascularization Era 

Over the last several decades, new treatment methods have emerged for patients with ACS such as percutaneous coronary intervention (PCI), fibrin specific fibrinolytic therapy, high-intensity statins, potent antiplatelet agents, and renin-angiotensin system inhibitors. This evolution has prompted reexamination of the role of long-term BB therapy in patients with preserved LV systolic function (commonly defined as an LVEF ≥40%-50%)–with conflicting results.  A 2014 post hoc analysis of CHARISMA (a trial evaluating clopidogrel use in stable CV disease) found that long-term BB therapy was associated with a reduction in recurrent MI but not improvements in overall/CV mortality. The 2018 CAPITAL trial evaluated long-term carvedilol use in 800 patients with ST-elevation MI treated with PCI and LVEF ≥40% and did not show a clear long-term outcome benefit. The 2024 REDUCE-AMI trial, which randomized >5,000 patients with acute MI treated with PCI and an LVEF ≥50% to BB (metoprolol or bisoprolol) or placebo found no difference between arms in the composite of death or recurrent MI at 3.5 years of follow up. Meanwhile, the 2024 ABYSS trial looked at withdrawing vs continuing BBs in ~4,000 patients already on BB therapy for prior MI with a preserved EF, and failed to show non-inferiority of the BB interruption group (primarily driven by increased hospitalizations in the interruption group).

Most recently, the 2025 REBOOT-CNIC and BETAMI-DANBLOCK trials tried to provide further clarity on the BB debate–yet again, with differing results. REBOOT-CNIC enrolled ~8,500 patients with ACS treated with PCI and an LVEF ≥40% to a BB (most received bisoprolol) or placebo. At 3.7 years, there was no difference in mortality, reinfarction or HF hospitalization between groups. By contrast, BETAMI-DANBLOCK, which enrolled just over 5,500 patients with ACS treated with PCI and LVEF ≥40% found that BB therapy was associated with a significant reduction in the primary endpoint of death or major adverse cardiac events, driven mainly by fewer MIs in the BB arm. In a subgroup analysis, the benefit seemed strongest in patients with mildly reduced LVEF, 40-49%.

These discrepancies spurred pre-specified pooled and individual patient-level meta-analyses to definitively answer this question. In a 2025 meta-analysis of CAPITAL, REBOOT-CNIC, and BETAMI-DANBLOCK, Rosello et al. assessed the efficacy of BBs in 1,885 patients with mid range LVEF (40-49%) and a recent MI. In this mildly-reduced EF patient population, BB therapy was associated with a reduction in the primary outcome of a composite of all-cause death, new MI, or HF.  Finally, in the 2025 Beta Blocker Trialists’ Collaboration Study meta-analysis, authors evaluated the benefit of BB therapy in those with a preserved LVEF (>50%). Among 17,801 patients included (from the CAPITAL, REDUCE-AMI, REBOOT-CNIC, and BETAMI-DANBLOCK), there was no difference in the primary composite outcome of all-cause mortality, MI, or HF between the BB and no-BB groups.  There was a numerical but non-statistically significant reduction in the number of recurrent MI favoring BB use. 

Putting it Together

These meta-analyses help us to put all the recent data together. Patients with a mildly reduced LVEF (40-49%) after an MI treated with PCI appear to derive a mortality benefit from long-term BB therapy, whereas patients with an LVEF ≥50% do not. Of course, it’s important to keep in mind that these trials largely excluded patients with another indication or contraindications for BB therapy (including rate control for atrial fibrillation, uncontrolled hypertension, or heart failure). The most recent AHA/ACC guidelines on ACS give early BB initiation a Class 1A recommendation for use in patients with ACS, and the AHA/ACC guidelines on CCD give BBs a Class 1A recommendation for use in those with prior MI and LVEF ≤40% and a Class 2B recommendation to reassess the utility of BB therapy in patients with prior MI and LVEF >50% after 1 year of therapy.  Both sets of guidelines predate the most recent 2025 BB trials and the subsequent meta-analyses, but there have been calls for change.  Ultimately, many questions remain, related to differences in patient characteristics (STEMIs vs NSTEMIs), optimal timing of initiation or discontinuation, duration of therapy, and which BB is best. Luckily, more trials are coming, including the SMART-DECISION (comparing BB discontinuation after 1 year of therapy to continuation) and ABBREVIATE (de-adoption of BB in patients with stable ischemic heart disease) trials, which aim to clarify some of these remaining questions.

Read The 2025 Guidelines Here!

Digestifs

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

Consolidate your learning with a Quiz!  

This week on The Curbsiders: Episode #505 covers a dizzying array of tips and tricks to help you manage….you guessed it, Dizziness! Dr. David Hale covers this topic from start to finish so that you can identify red flag symptoms and diagnose and treat your patients seamlessly. 

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Until next time, keep that brain hole digesting! 

The Curbsiders Digest

Issue 71

Editor in Chief: Nora Taranto MD

Banner: Kate Grant  MBChB, DipGUMed

Jennifer DeSalvo,  Joshua Gilman,  Alyssa Mancini, Beth Gasperlin, and Nora Taranto report no disclosures.

Kate Grant reports no disclosures. 

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