Digest 73: Changing January Landscapes

January 30, 2026 | By Nora Taranto

Welcome Back to The Curbsiders Digest!

In this issue we discuss the changing January landscapes, plus CREST-2 and Carotid Stenosis Management, Tirzepatide and Oral GLPs, Antidepressant Tapering, and Age-adjusted D-Dimers 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 73

01/30/2026

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.

Jennifer DeSalvo MD, Laura Glick MD, Joshua Gilman MD, Alyssa Mancini MD

• GLP/GIPs continue their winning streak! The SURPASS-CVOT non-inferiority trial randomized ~13,000 patients with type 2 diabetes (DM2) and ASCVD to receive either the dual GLP/GIP-1 receptor agonist tirzepatide (max dose of 15mg) or GLP-1 receptor agonist dulaglutide (max dose of 1.5mg).  After a median follow up of four years, the primary outcome (a composite of death from any cardiovascular (CV) cause, myocardial infarction (MI), or stroke) occurred in 12.2% of the tirzepatide group compared to 13.1% in the dulaglutide group (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.83 – 1.01, p=0.003 for non-inferiority; p=0.09 for superiority). Secondary outcomes numerically favored tirzepatide including death from CV causes (5.6% vs 6.2%), death from any cause (8.6% vs 10.2%), MI (4.7% vs 5.4%), reduction in A1c (-1.66% vs -0.88%) and body weight reduction (-11.8% vs. -4.8%). Both treatment arms had similar rates of drug discontinuation (~20%). Adverse events were also common in both, the most common of which were gastrointestinal. (JG)
• Age-ADJUSTed D-dimer cutoffs to rule out DVT?  JAMA recently published the results of ADJUST-DVT, a multicenter, multinational prospective study aiming to validate the use of an age-adjusted D-dimer cutoff (age x 10 in those aged >50) to safely rule out lower extremity deep vein thrombosis (DVT). In this study, 3205 individuals (median age 59 years, 54% female) presented to the emergency department with suspicion for a lower extremity DVT.  2169 individuals (68%) had a low/intermediate or unlikely pretest probability of having a DVT, based on Wells score.  In this patient subset, 24.5% had a D-dimer < 500 ug/L (the standard D-dimer cutoff), and 7.4% had a D-dimer level between 500 ug/L and their age-adjusted cutoff.  In the latter group, none had a confirmed venous thromboembolism (VTE) within three months of follow up. Therefore, use of the age-adjusted cutoff resulted in a 7.4% absolute increase in the proportion of patients in whom DVT could be ruled out. In patients aged > 75, using the age-adjusted cutoff increased the proportion of negative D-dimer from 8.7% to 26.1%, without any false-negative tests. (AM) 
• Debunking deprescription of antidepressants. In a systematic review and meta-analysis of 76 trials just published in Lancet Psychiatry–encompassing more than 17,000 patients with fully or partially remitted illness (mean age 45 ± 15 years; 68% female)–investigators examined how different antidepressant deprescribing strategies influence risk of disease relapse. The analysis compared abrupt discontinuation with fast tapering (≤4 weeks), slow tapering (>4 weeks), dose reduction (≤50% of the minimum effective dose), or continuation of antidepressants, with or without psychological support, over a mean follow-up of 46 weeks. Slow tapering combined with psychological support, antidepressant continuation (especially paired with psychological support), and reduced-dose continuation all reduced the risk of depression relapse compared to abrupt discontinuation (with fast tapering strategies showing no improvement compared to abrupt discontinuation). Evidence in remitted anxiety remains limited. The authors conclude that clinical guidelines should promote individualized deprescribing strategies—emphasizing gradual tapering and structured psychological support. (JD) 
• A TOP Trial for Transfusion. The TOP trial (Transfusion Trigger after Operations in High Cardiac Risk) recently published in JAMA compared liberal versus restrictive postoperative red-cell transfusion strategies in 1,428 U.S. veterans at high risk for cardiac events undergoing major vascular or general surgery. Participants with postoperative anemia (hemoglobin <10 g/dL) were randomized to either a liberal strategy (transfusion trigger <10 g/dL) or a restrictive strategy (transfusion trigger <7 g/dL). The primary outcome—a composite of 90-day all-cause mortality or major ischemic events (myocardial infarction, coronary revascularization, acute kidney failure, or ischemic stroke)—was not significantly different between the liberal and restrictive arms (9.1% vs 10.1%; RR 0.90; 95% CI, 0.65–1.24), indicating no clear benefit with liberal transfusion in this high cardiac-risk surgical population. Interestingly, a secondary analysis did find a lower rate of non-MI cardiac complications (new arrhythmias, heart failure, nonfatal cardiac arrest) in the liberal transfusion group (5.9% vs 9.9%). (LG) 
• An Oral GLP Approval. The U.S Food and Drug Administration (FDA) recently approved the once-daily oral semaglutide 25 mg (Wegovy® tablet) for chronic weight management in adults who are obese or overweight with at least one weight-related comorbidity, and for reduction of major adverse cardiovascular events in adults who are obese or overweight with established cardiovascular disease. This approval represents the first oral glucagon-like peptide-1 (GLP-1) receptor agonist indicated for weight management. Approval was based on data from the OASIS and SELECT trials. The Wegovy pill, which is currently available in the United States (as of January 2026), is indicated as an adjunct to a reduced-calorie diet and increased physical activity. It is administered once daily on an empty stomach with gradual dose escalation to a maintenance dose of 25 mg to improve tolerability. (LG)

Palate Cleanser

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

With the dawn of the digital curbside via secure chat messaging prompting increased use of the electronic health record (EHR), a recent retrospective study analyzed gender differences contributing to unequal digital workload burden among over 200 Internal Medicine and Internal Medicine-Pediatric physician trainees and faculty working in the hospital. Witte et al found that although female and male physicians worked a similar number of hours (9.5 vs 9.3 hours, p= 0.4), both female trainees and faculty spent more time engaging digitally in the EHR (248 vs. 222 min/day; p < .001) and secure chat (38 vs. 34 min, p < .001), and exchanged more daily messages (62 vs. 53 sent; 56 vs. 48 received, both p < .001). These trends remained consistent after faculty transitioned to a swing shift model despite a reduction in overall number of working hours. Additionally, the authors noted, “although modest, these differences accumulate; for [inpatient] faculty in a week-on/week-off model, this equals 13 extra hours of messaging and over 70 additional hours in the EHR annually… these patterns are unlikely to be solely self-imposed; rather they may stem from a nexus of external expectations, communication styles shaped by social norms, and subtle biases in team dynamics… several studies have associated higher EHR workload with burnout and reduced job satisfaction.” This study’s findings are also consistent with the digital workload gap observed in outpatient settings and may indicate a need to further investigate system-level workflow redesign strategies to promote digital workload efficiency and equity. 

– Jennifer DeSalvo MD 

The Main Course

Joshua Gilman MD

Asymptomatic Carotid Stenosis: Does Medical Management Finally Win?
The management of asymptomatic carotid artery stenosis has been quite controversial. For decades, clinical practice favored surgical intervention with endarterectomy over medical management alone, but modern  therapies–and less invasive procedures, such as stenting–have challenged the surgical approach. The CREST-2 trials, just published in NEJM, have now added new evidence that will likely challenge traditional practice patterns and reshape clinical guidelines.

First, some background on the disease. Asymptomatic carotid stenosis increases the risk of neurological ischemic events, including ischemic stroke, transient ischemic attack (TIAs), and transient monocular vision loss. Historical data from the 1990s suggested the risk of stroke in patients with severe (70-99%) carotid artery stenosis was >10% with medical therapy alone (noting medical therapy in many of these studies was aspirin alone). However, contemporary trials have suggested a much lower risk of stroke in asymptomatic patients (<1-2% per year) with modern medical management (aspirin, lipid lowering agents, anti-hypertensive agents, glycemic control, and lifestyle modification such as smoking cessation, weight loss, physical activity, and dietary modifications). But while stroke rates may be low, observational studies have shown that patients with asymptomatic carotid disease experience high rates of myocardial infarction and cardiovascular death, underscoring the importance of atherosclerosis management and risk factor modification.

The First Generation of Endarterectomy and Stenting Trials 
Three trials from the 1990s and 2000s established carotid endarterectomy (CEA) as the standard treatment for patients with severe, asymptomatic carotid stenosis: the Veterans Affair Study, the ACAS trial and the ACST trial. These trials showed an increase in perioperative risk of stroke or death, but a longer term reduction in stroke risk of ~1% per year. All trials enrolled patients with >60% carotid artery stenosis and compared CEA plus medical therapy to medical therapy alone. At the time of these trials, medical therapy typically consisted of a combination of aspirin and antihypertensives, with low rates of statin use.

Subsequently, carotid artery stenting (CAS) emerged in the mid 2000s as an alternative to CEA. The SPACE-2 trial, published in 2022, was the first to compare CEA, CAS and medical therapy in asymptomatic patients and found no difference between the groups– though the trial was stopped early due to slow enrollment. Additionally, a 2-year interim outcome analysis of the ESCT-2 trial, which compared CEA, CAS or medical therapy for both symptomatic and asymptomatic moderate/severe carotid stenosis showed no difference in outcomes. But this interim analysis also had a low number of patients and events on trial, and may have been underpowered. 

The Carotid Revascularization Endarterectomy vs. Stenting Trial 2 (CREST-2)
CREST-2 comprised two parallel, international, observer-blinded trials (a stenting trial and a surgical trial) enrolling 2485 patients with high-grade (≥70%) asymptomatic carotid stenosis. The stenting trial (n=1,245) compared intensive medical management (IMM) to CAS plus IMM,  and the surgical trial (n=1,240) compared IMM alone to CEA plus IMM. IMM consisted of antiplatelet therapy, medications to target a systolic blood pressure < 130mmHg and medications to target a low-density lipoprotein (LDL) cholesterol < 70mg/dL. Lifestyle factors (e.g. smoking cessation, glycemic control, weight) were also managed as needed. CREST-2’s primary outcome was a composite of stroke (ischemic or hemorrhagic) or death up to 44 days after randomization or ipsilateral ischemic stroke over the remainder of the 4 year follow-up.

In the stenting trial, the 4-year incidence of the primary outcome was 6.0% with IMM compared to 2.8% with CAS + IMM (absolute risk difference 3.2%, 95% CI 0.6-5.9, p=0.02, with a number needed to treat [NNT] of 31). From day 0-44 there were no strokes or deaths with IMM compared to 7 strokes and 1 death with CAS + IMM. For the rest of follow-up, the annual event rate of ipsilateral stroke was 1.7% with IMM compared to 0.4% with CAS + IMM (28 vs.7 ipsilateral strokes; 95% CI 1.78-9.31). Meanwhile, in the endarterectomy trial, the 4-year incidence of the primary outcome was 5.3% with IMM compared to 3.7% with CEA + IMM (absolute risk difference 1.6%, 95% CI -1.1-4.3, p=0.24). From day 0-44, there were 3 strokes with IMM, compared to 9 with CEA + IMM. For the remainder of follow-up, the yearly ipsilateral stroke rate was 1.3% with IMM compared to 0.5% with CEA + IMM (23 vs.10 ipsilateral strokes; 95% CI 1.13-5.00).

There are several important limitations to consider in interpreting CREST-2. First, there were very few events on study.  Furthermore, proceduralists had to undergo intense operator credentialing and patient anatomy was considered in screening procedures, potentially limiting generalizability. Lastly, the medical management arm could have been optimized, as a substantial proportion of patients had suboptimally controlled blood pressures, cholesterol and glycemic indices. An accompanying editorial importantly pointed out that for every 100 patients stented, approximately 4-5 patients will experience long-term benefit, while 1-2 will experience a peri-procedural stroke/death.

So where do we currently stand?
It seems likely that CREST-2 will ultimately shift management strategies away from surgery towards less invasive procedures like stenting. But the trial also importantly illustrates that intensive medical management may be powerful in and of itself.  As additional, potent medical therapies (e.g. PCSK9 inhibitors, GLP-1 agonists, and Lp(a) targeted therapies) become more widely available, the future of this disease may be managed more and more without procedures. Keep an eye out in coming months for guideline updates that reflect the CREST-2 results and this changing landscape.

Read the CREST-2 Results HERE!

Digestifs

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

Consolidate your learning with a Quiz!  

This week on The Curbsiders: Catch up this week on your Zs…by learning all the tips and tricks of sleep optimization and insomnia management with Ashley E. Mayson, PhD in Episode #512. We promise, this high-yield one won’t put you to sleep! 

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The Curbsiders Digest

Issue 73
Editor in Chief: Nora Taranto MD
Banner: Kate Grant  MBChB, DipGUMed

Jennifer DeSalvo,  Joshua Gilman,  Laura Glick, Alyssa Mancini, and Nora Taranto report no disclosures.

Kate Grant reports no disclosures.    

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