Digest 80 – Statins at the forefront. Plus automated oxygen titration in the critically ill, finerenone in CKD, and more

September 26, 2026 | By Nora Taranto

Welcome Back to The Curbsiders Digest!

In this issue we discuss everything from statins at the forefront, plus automated oxygen titration in the critically ill, finerenone in CKD, and more. Effortlessly absorb important medical news, with our monthly newsletter featuring easily digestible analysis of the latest practice-changing articles, and of course…bad puns. 

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Issue 80

09/25/2026

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, Joshua Gilman MD, Alyssa Mancini MD

YEARS algorithm to exclude PE. JAMA recently published the results of the Hydra study, an open-label, randomized, noninferiority trial that compared the safety and efficiency of the YEARS algorithm with CT pulmonary angiography (CTPA) only to rule out acute pulmonary embolism (PE) in patients with active cancer. 698 patients (median age 65, 60% female) with active cancer and suspected acute PE were recruited from emergency departments or medical units in 21 hospitals across Europe. Patients were randomized 1:1 to receive diagnostic management by CTPA only vs. by the YEARS algorithm, which assesses pretest probability based on 3 clinical items (signs of deep vein thrombosis, hemoptysis, PE the most likely diagnosis) and applies a probability-dependent D-dimer threshold below which acute PE can be safely ruled out and above which risk-dependent CTPA is performed. The YEARS algorithm’s diagnostic failure rate was 1.8% compared with 5.5% with CTPA only, for an absolute risk difference of -3.7%, which met criteria for noninferiority. Diagnostic management of PE without the need for CTPA was carried out for 22% of patients in the YEARS group. (AM) 

GLP-1 use and Breast Cancer. JCO Oncology Practice recently published the results of a retrospective cohort study conducted at a major academic center and affiliated sites looking at breast cancer incidence and glucagon-like peptide-1 receptor agonist (GLP-1) use. The study included  >100,000 women aged 45-80 (median age 61) with a BMI ≥ 25 who had documented breast imaging results. To address confounding, 1:1 case-control matching using propensity scores based on age, race, ethnicity, highest BMI, breast density, and history of type 2 diabetes was performed. GLP-1 use, defined as an initial prescription prior to the imaging date, was associated with a lower incidence of breast cancer (OR 0.649; 95% CI 0.57 – 0.74, p<0.0001). Results were similar in the matched logistic regression. (AM) 

Should we anticoagulate everyone with AFib? The benefit of anticoagulation (AC) in atrial fibrillation with an elevated stroke risk (CHA2DS2-VASc score ≥2 for men and ≥3 for women) has been well established, but the role of AC in an intermediate risk group (score of 1 in men and 2 in women) remains unclear. The recently published SINGLE-AF trial in NEJM sought to answer this very issue! This multicenter, open-label, superiority trial out of South Korea randomized 1,803 patients with intermediate-risk AFib to direct oral anticoagulant (DOAC) therapy vs no AC. At 2 years there was a 69% reduction in the cumulative incidence of stroke, systemic embolisms, major bleeding or death from any cardiovascular causes favoring the DOAC group (absolute difference of -1%, 0.5% vs 1.5%, p=0.028). There were a total of 3 strokes in the DOAC arm compared to 10 in the no AC arm. Major bleeding was not different between the groups. So anticoagulate away? It is worth noting the relatively low incidence of stroke in this group overall–though it may also be worth taking into account the burden of AF experienced to help with risk stratification. (JG) 

More fodder for finerenone! The INFINITY meta-analysis, published in The Lancet, pooled data from 3 randomized trials of finerenone, a non-steroidal mineralocorticoid receptor antagonist, in patients with chronic kidney disease (CKD), with and without T2DM, to assess efficacy across the full spectrum of CKD. 14,574 patients (mean age 64, 31% female), randomized to finerenone vs placebo on top of usual care for CKD, were included. Over a median follow-up of 3.1 years, finerenone reduced the risk of composite kidney outcome (≥57% decline in eGFR or kidney failure) by 24% compared to placebo (HR 0.76, 95% CI 0.68-0.86, p<0.0001). There was also a 20% relative reduction in composite cardiovascular outcome (heart failure hospitalization or cardiovascular death) favoring finerenone (HR 0.80, 95% CI 0.70-0.91, p=0.0006). Finerenone also lowered the risk of all-cause death (HR 0.88, 95% CI 0.79-0.99). The effects of finerenone on both outcomes were consistent across diabetes status as well as CKD etiology, baseline eGFR, urine albumin creatinine ratio and SGLT2i use. There was almost double the amount of hyperkalemia in the finerenone group (14.3% vs 7.6%), but termination of the drug was uncommon and hospitalization for hyperkalemia was even more rare. (JG) 

“Hey Alexa, Adjust the Oxygen…” JAMA Internal Medicine recently published a multicenter, randomized clinical trial (SAVE-O2 AI) evaluating whether autonomous supplemental oxygen titration in hospitalized adult patients can maintain normoxemia better than manual oxygen titration. Approximately 300 acutely ill hospitalized adult patients (median age 66, 54% female) receiving supplemental oxygen were randomized to autonomous oxygen titration versus usual care for 72 hours following randomization. The primary outcome – mean proportion of time spent in normoxemia (SpO2 90-96%) – was improved in the autonomous oxygen titration group compared to usual care group (85% vs 63%; adjusted risk difference 21 percentage points [pp]; 95% CI 18-25 pp; P<0.001). Secondary outcomes also demonstrated decreased time spent in hypoxemia and hyperoxemia in the autonomous oxygen titration group versus usual care group. (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.

Health Consequences of 9/11 

It’s difficult to believe this year marks the twenty-fifth anniversary of the September 11^th terrorist attacks – a milestone which also serves as an important reminder that, for many patients, the health consequences of that day did not end when the dust settled. In a piece recently published in JAMA Internal Medicine, Dr. Steven Phillips calls clinicians to clarify patients’ exposure history and confirm if patients are eligible for or enrolled in the federal World Trade Center Health Program. Patient survivors include local responders, residents, workers, students, or child/adult daycare attendants. Decades later, individuals may be suffering from subsequent long-term chronic physical and mental health conditions, including various cancers, namely thyroid, prostate, melanoma, tonsil, and lung, in addition to chronic rhinosinusitis, gastroesophageal reflux, obstructive and restrictive lung diseases, post-traumatic stress disorder, depression, and anxiety. Dr. Phillips implores clinicians to recognize patients’ exposure and guide eligible patients to enroll in the program to qualify for no-cost treatment. For patients enrolled in the program, clinicians should ensure patients receive appropriate care for certified conditions and encourage patients to reconnect with the program when a new condition may be certifiable. Twenty-five years later, the past may still be part of the present, sometimes waiting quietly in the social history for a clinician to ask the right question.

– Jennifer DeSalvo MD 

The Main Course

Alexander Chaitoff MD, MPH 

The evolving conversation about the benefits of statins for older adults

There is a special kind of angst clinicians face when telling an older adult, already on multiple medications, that they might need to start yet another one. Often, the medication being recommended is a statin.

While most older adults qualify for statins by guidelines, it has been reasonable to wonder how much benefit some patients are getting, as most primary prevention trials that informed the guidelines included participants with average ages of 52-62.  Furthermore, for patients already on statin therapy, some evidence suggested a “legacy effect“—the idea that statins might continue providing cardioprotection even after a patient stops the medication, potentially due to durable changes in plaque composition —raising the question of whether statins truly need to be lifelong medications.  There are also costs and harms to consider, as some high-intensity statins were, until recently, expensive brand-name medications. Further, statins were widely blamed for myalgias and cognitive impairments, among other side effects.

This all made it reasonable for people to question the use of statins in some older adults. But over the past several years, the conversation shifted. Meta-analyses pooling multiple trials overcame the power limitations of any single study and demonstrated that cardiovascular benefit persists even among the oldest patients. Meanwhile, rigorous n-of-1 trials and meta-analyses revealed that most statin-associated side effects are better explained by the nocebo effect than by any pharmacologic action. But while this evidence is reassuring, it still doesn’t get to the heart of the question – Is it safe to deprescribe statins in older adults being treated for primary prevention? And is it beneficial to start statins in older adults who’ve never been on one?

Thankfully, two trials have just come out that speak much more directly to the issue.

Starting statins for primary prevention in older adults
The STAREE trial asked whether initiating atorvastatin (40 mg daily) for primary prevention benefits community-dwelling older adults, randomizing 9,971 participants ≥70 years old (mean age 74.7) to atorvastatin versus placebo. Importantly, the trial excluded adults with any history of cardiovascular disease, diabetes, or dementia – this was a primary prevention trial. At a median follow-up of 5.9 years, atorvastatin significantly reduced major cardiovascular events compared with placebo (10.9 vs. 15.5 events per 1000 person-years, HR 0.7, 95% CI 0.61 – 0.82, p<0.001) compared with placebo. However, this was driven mostly by nonfatal MI and coronary revascularization, not reductions in cardiovascular mortality, for example. In fact, disability-free survival did not differ between groups.

Stopping statins for primary prevention in older adults
Meanwhile, the SAGA/SITE trial investigated whether discontinuing statins is non-inferior to continuing statins with respect to all-cause mortality among adults aged >75 years without a history of atherosclerotic cardiovascular disease who had been on statins for at least 1 year. Unlike the STAREE trial, they did include patients with diabetes (around 30% of the cohort). After excluding patients with life expectancy ≤3 months or dementia, the study enrolled 1,160 participants (median age 80). At 3 years of follow-up, all-cause mortality was similar between groups (7.9% continuation vs. 7.2% discontinuation), with no significant differences in major cardiovascular events, adverse events, or quality of life.

Where does this leave us now?
These trials suggest that the observational studies might have been pointing in the right direction after all. The deprescribing trial showed no real difference between groups, which may be consistent with a legacy effect. The prescribing trial showed cardiovascular benefit, matching what the meta-analyses had already suggested.

But the takeaways are nuanced. Even if a myocardial infarction doesn’t immediately cause mortality, having one isn’t preferable, and our usual disability metrics may not fully capture that.  Imagine a myocardial infarction that leads to a revascularization procedure that leads to lifelong antiplatelet therapy that leads to higher bleeding risk; these are downstream cascades that trials don’t always measure well. And in the deprescribing trial, yes, patients got off one medication. And yes, this was non-inferior to continuing it–but only when powered to detect a fairly large effect size. Patients who stopped their statin also had no better quality of life. So should a generic, affordable medication that may still offer a small benefit be stopped just because non-inferiority was demonstrated? Both trials also excluded patients with dementia, a reminder that trials can only generalize to the populations studied.

The answer, as usual, is shared decision-making. These results should make us feel better about not using statins in the right older adult, but we shouldn’t overread the evidence to assume all older adults would be just as well off without them. It’s a call to feel more confident in personalizing care: after these trials, both starting and stopping statins in older adults seem like reasonable choices, depending on the patient in front of you.

Read the SAGA/SITE study HERE and the STAREE study HERE!

Digestifs

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

Consolidate your learning with a Quiz!  

This week on The Curbsiders: Get Hip with Episode #539: TikTok Trends in Medicine. In this episode, Jessica Malaty Rivera dives into the evidence behind viral trends on tiktok (red light masks, peptides, etc.) and the influencer incentives behind some of this content.  

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The Curbsiders Digest

Issue 80
Editor in Chief: Nora Taranto MD
Banner: Kate Grant  MBChB, DipGUMed

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

Alex Chaitoff reports consultancy for Alosa Health

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