Digest 69: From VTE to VT

September 26, 2025 | By Nora Taranto

Welcome Back to The Curbsiders Digest!

In this issue, we take a look at extended Apixaban for VTE prevention, potassium for arrhythmia prevention, and Digitoxin for HF in the spotlight, 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 69

09/26/2025

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. 
-Jennifer DeSalvo MD, Joshua Gilman MD, Alyssa Mancini MD

• Extended Anticoagulation After Provoked VTE. For patients with provoked venous thromboembolism (VTE) and ongoing risk factors, low dose apixaban for 12 months led to a lower risk of symptomatic recurrent VTE compared to placebo, per a recent study published in NEJM. This was a single-center, double-blind, randomized trial of 600 adults (mean age 69, 57% female) with VTE who had a transient provoking factor, at least one enduring risk factor, and had already completed >3 months of anticoagulation. Patients were randomized to receive oral apixaban 2.5 mg twice daily vs. placebo for 12 months. The most common provoking factors were surgery (34%), immobility (31%), trauma (19%), and acute medical illness (18%). The most common enduring risk factors were chronic inflammatory/autoimmune disorder (52%), BMI >30 (48%), atherosclerotic cardiovascular disease (29%), and chronic lung disease (22%). Symptomatic recurrent VTE occurred in 1.3% of patients with apixaban and 10% with placebo (HR 0.13; 95% CI 0.04 to 0.36, p<0.001). Major bleeding occurred in 1 apixaban patient and none with placebo, with clinically relevant non-major bleeding in 4.8% of apixaban patients and 1.7% of placebo patients. (AM) 
• To Hold or Not To Hold.  In patients with inflammatory rheumatic disease (IRD), should we hold immunomodulatory agents (IA) when patients are infected? A recent study published in Clinical Infectious Diseases randomized patients with IRD on IA to either continue or temporarily interrupt IA treatments when experiencing their first clinically relevant infection. 474 of 1142 enrolled patients developed a clinically relevant infection (mostly mild to moderate).  The primary outcome of serious infections (i.e. those requiring hospitalization or IV treatment) occurred in 5.2% of interruption-group patients and 3.7% of continuation-group patients–with an adjusted risk difference of 1.7% (95% CI -1.99 to 5.39%) in favor of continuation.  When secondary analyses accounted for non-adherence (only 46% of patients in the interruption group actually held their IA), the risk difference was 4.5% (95% CI -7.32 to 16.34) in favor of continuation. The most common infections were non-COVID-19 respiratory, COVID-19, skin, and urogenital infections. The median duration of infection was similar between the groups, as was the occurrence of rheumatologic disease worsening. (AM) 
• Replete the K!  The POTCAST Trial, just published in NEJM, sought to assess the efficacy and safety of intentional potassium increases in patients at high risk for ventricular arrhythmias. This multicenter, open-label trial randomized 1200 patients at high-risk for ventricular arrhythmias (defined as those with defibrillators (ICDs or CRT-Ds)) with a baseline potassium level of < 4.3 mmol/L to receive treatment to increase potassium levels (high-potassium group) or standard of care. Patients in the high-potassium group were educated on potassium-rich diets and received potassium supplementation, mineralocorticoid receptor antagonists (MRAs) or both to achieve a target potassium level of 4.5-5.0 mmol/L.  Over 39.6 months of median follow-up, the primary endpoint (a composite of sustained VT or appropriate ICD therapy, unplanned hospitalization for arrhythmia or heart failure, or death) occurred less in the high potassium group compared to the standard-of-care group (22.7% vs 29.2%, HR 0.76 [0.61-0.95] p=0.01). This was primarily driven by a reduction in appropriate ICD therapy (15.3% vs 20.3%), with no difference in deaths. At trial conclusion, serum potassium levels were 4.36 mmol/L in the high-potassium group compared to 4.01 mmol/L with standard-of-care, and approximately 2/3 of high-potassium group patients were taking MRAs. (JG) 
• Is dig making a comeback? NEJM just published the DIGIT-HF trial which evaluated the efficacy and safety of low digitoxin (a cardiac glycoside similar to digoxin but eliminated by enterohepatic excretion if renal function is impaired) at low concentrations in patients with Heart Failure with reduced Ejection Fraction (HFrEF). This multicenter, double-blind, placebo-controlled trial randomized 1240 patients with HFrEF (and EF <40%) who were already on guideline-directed medical therapy (GDMT) to digitoxin vs placebo in addition to GDMT.  Levels of serum digitoxin were monitored every 6 weeks and adjusted for a target range of 8-18ng/mL. The mean EF was 29%, roughly 66% of patients had NYHA Class 3 symptoms and the majority of patients were on a RAAS-inhibitor, beta blocker, and mineralocorticoid receptor antagonist (with about 20% on an SGLT2 inhibitor). At 36 months of median follow-up, the primary outcome (composite of death from any cause or first hospital admission for worsening heart failure) occurred less in the digitoxin group compared to placebo (39.5% vs 44.1%; HR 0.82 [0.69-0.98] p=0.03). A serious adverse event occurred in 4.7% of the digitoxin group vs 2.8% of the placebo group (primarily cardiac disorders including ventricular fibrillation). There was a significant amount of drug discontinuation in both groups. (JG)
• Go with the Flow? Idiopathic normal-pressure hydrocephalus (NPH), a neurologic disorder featuring abnormal cognition, gait, and bladder control, is commonly treated with shunt surgery–but the effectiveness of shunting remains uncertain. A recent double-blind, placebo-controlled trial published in NEJM randomized 99 participants who responded to temporary cerebrospinal fluid drainage (with improved gait velocity) to an open-shunt valve setting (opening pressure 110 mm of water) or placebo valve setting (opening pressure>400 mm of water). The primary outcome of change-in-gait-velocity 3 months after surgery was greater in the open-shunt group (mean change 0.23 m per second) compared to placebo (mean change 0.03 m/sec; treatment difference of 0.21 m/sec, 95% CI 0.12 to 0.31, P<0.001). The open-shunt group experienced significantly greater improvement in gait and balance (by Tinetti scale) than the placebo group, but not in cognition or incontinence (measured by MOCA/Overactive Bladder Questionnaire, respectively). Adverse events included more falls in the placebo group (46% vs 24%), increased subdural bleeding and positional headaches in the open-shunt group, and a similar rate of cerebral bleeding in both groups. (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.

Popularized during the COVID-19 pandemic, telehealth has emerged as an innovative model to improve access to healthcare for diverse patient populations. Koh et al. recently published an article in JAMA Internal Medicine sharing their experience utilizing telehealth for medical and behavioral health visits among people experiencing homelessness, a group historically plagued by fragmented care and poor outcomes. The authors attribute their success in improving healthcare access and engagement using telehealth to the high rate of mobile phone ownership in this population, which eliminates barriers to in-person appointments and increases the flexibility of interactions with healthcare providers. However, significant challenges of this telehealth model remain: inconsistent phone service due to variable plan costs, high rates of device loss or theft, digital illiteracy, and the intrinsic limitations of telehealth – including the inability to perform physical exams and reduced personal connection. To transition from innovation to sustainability, the authors suggest systemic solutions: government-subsidized phones, dedicated telehealth centers with private rooms for Wi-Fi and phone charging, equipment to assist with virtual exams, and onsite staff to assist with digital literacy. As telehealth continues to evolve, adapting it for vulnerable populations like the unhoused will be key to its long-term value in equitable care delivery.

– Jennifer DeSalvo MD 

The Main Course

Alexander Chaitoff MD, MPH

Big news in blood pressure
You know how the wait between seasons of your favorite television show can seem like an eternity? The medical world endured a similar feeling as we waited 8 years for new American College of Cardiology/American Heart Association (ACC/AHA) hypertension treatment guidelines. Join us for a recap of some of the biggest changes in the 2025 Update.

Looking to PREVENT cardiovascular disease
One of the biggest updates is the inclusion of the PREVENT score to guide treatment decisions. The PREVENT (Predicting Risk of Cardiovascular Disease Events) score is a new cardiovascular risk assessment tool. PREVENT replaces the Pooled Cohort Equations (PCE), which were derived (as the name suggests) by pooling cohorts of patients and looking at what factors correlated with developing atherosclerotic cardiovascular disease over a 10-year time horizon. Since the PCE tool was developed in the 2010s using data from prior decades, there was concern that it overestimated cardiovascular risk, especially in certain populations. PREVENT was therefore developed on newer patient cohorts using more contemporary administrative claims data, and generally estimates a lower risk of cardiovascular disease for many patients. Two other important differences to note: Unlike the Pooled Cohort Equations, PREVENT allows clinicians to calculate the risk for total cardiovascular disease, atherosclerotic cardiovascular disease, and heart failure, and PREVENT can be used to calculate both 10-year and 30-year risks.

The 2017 guideline recommended using medications to treat adults with blood pressure >140/90 mmHg or >130/80 if they had >10% risk over 10-years as assessed by the Pooled Cohort Equation. The updated 2025 guidelines still recommend medication for those with blood pressure >140/90 mmHg, but they now recommend immediately treating anybody with blood pressure >130/80 mmHg and >7.5% risk by PREVENT (Section 5.2.2). Even for those with <7.5% total cardiovascular disease risk, the guidelines recommend initiating treatment within 3-6 months if lifestyle changes alone have not decreased blood pressure levels to <130/80, which is a more forceful recommendation than previous ones.

And the goal isn’t just to shoot for 130/80 mmHg anymore – for those who tolerate it, the 2025 guidelines explicitly mention that aiming for 120/80 mmHg, the goal in the SPRINT trial, may be optimal.

Check for resistant hypertension
Another big change is more attention paid to primary aldosteronism (Section 3.2.3.1). The 2025 guidelines state that all patients with resistant hypertension should be screened regardless of the presence of hypokalemia.  The ACC/AHA recommendation is one step removed from the 2025 Endocrine Society Primary Aldosteronism Guideline recommendation, which suggests screening for any patient with hypertension.  The 2017 ACC/AHA guidelines acknowledged that the negative predictive value of a normal potassium level was poor,  and the 2025 guidelines build on this by recommending a lower bar for screening – including any patients with resistant hypertension, hypokalemia, OSA, incidental adrenal mass, family history of early-onset hypertension, or stroke at a young age. They’ve also changed recommendations to make it logistically easier to obtain renin and aldosterone levels: to avoid delays in screening, the guidelines are now explicit that most antihypertensives can be continued before initial testing, with the exception of mineralocorticoid receptor antagonists. Furthermore, in those who have resistant hypertension that can’t be controlled with medication, the 2025 guidelines newly endorse renal denervation (Section 5.6) given recent evidence from sham-controlled trials.

Be aggressive to prevent kidney decline
Another area in which the guidelines recommend more aggressive workup and treatment is in those at risk for kidney disease. In the 2017 guidelines, workup for renal disease with urinary albumin-to-creatinine ratio was considered optional, but it is now a recommended test (Section 3.1.2). Furthermore, the guideline is much more strongly worded about using RAAS inhibition as the first line for patients with hypertension and kidney disease or diabetes, with wording changed from something that “can be considered” to something that is recommended.

The message: treat high blood pressure
These guidelines are filled with changes (See Table 1). Blood pressure control is now unequivocally recommended to prevent cognitive decline, pregnant people with hypertension are recommended to be counseled on aspirin use, and a high-potassium diet is recommended for those without kidney disease.  Nondihydropyridine calcium channel blockers (like diltiazem) are out as recommended first-line agents, while thiazide diuretics, dihydropyridine calcium channel blockers, and ACE inhibitors and ARBS are still in (Table 13). Combination pills, which are associated with better adherence and blood pressure control than prescribing multiple monotherapies, are now given a lot of real estate in the guidelines (Section 5.2.4).

There are a lot of details, we know (and there are many more, so check the guidelines out on a rainy afternoon!).  But if you are looking for a theme, it is that the recommendation to aggressively treat hypertension has never been stronger.

Read The Study Here!

Digestifs

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This week on The Curbsiders: Episode #499 tackles all the DOAC dilemmas you didn’t even know you had (but you definitely did!). In this episode, Dr. Jori May tackles the nuances of treatment failure, use of DOACs in obesity, and so much more.  

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The Curbsiders Digest

Issue 69

Editor in Chief: Nora Taranto MD

Banner: Kate Grant  MBChB, DipGUMed

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

Alex Chaitoff reports consultancy for Alosa Health. 

Kate Grant reports no disclosures. 

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