Hypokalemia and low-normal potassium levels (<4.0 mEq/L) are known risk factors for ventricular arrhythmias in patients with cardiovascular disease. Consequently, maintaining high-normal potassium levels (4.5 - 5 mEq/L) in these patients may be beneficial. To examine the issue, researchers performed the POTCAST trial, where 1200 patients with an ICD (underlying heart disease: heart failure - 64%, ischemic heart disease - 50%, nonischemic cardiomyopathy and primary arrhythmia disorders - 50%) and a potassium of less than 4.3 mEq/L were randomized to a target potassium level of 4.5 to 5.0 mEq/L (high-normal group) or standard care. In the high-normal group, potassium levels were increased using potassium supplements, mineralocorticoid receptor antagonists (spironolactone or eplerenone), or both. Guidance on a potassium-rich diet was also provided, and potassium-losing diuretics were stopped if able. After a median follow-up of 39.6 months, the primary outcome (a composite of documented sustained ventricular tachycardia or appropriate ICD therapy, unplanned hospitalization for arrhythmia or heart failure, or death from any cause) was significantly lower in the high-normal group compared to standard treatment (22.7% vs 29.2%, P=0.01) Appropriate ICD therapy or documented ventricular tachycardia and unplanned hospitalization for arrhythmia accounted for the majority of the difference in the primary end point. Hospitalization for hyperkalemia or hypokalemia was similar between groups.

The protocol for achieving the target range included initial visits every other week for blood tests and medication adjustments. The median duration for this intensive adjustment period was 85 days. Despite this rigorous protocol, only 42% of participants in the high-normal potassium group achieved a target potassium level. This type of frequent monitoring would be impractical in most routine outpatient practices. However, this study does offer an important takeaway: the beneficial effect was not dependent on achieving the high-normal target, suggesting the goal should be to avoid hypokalemia or low-normal potassium levels in this patient population.

• Increasing the Potassium Level in Patients at High Risk for Ventricular Arrhythmias, NEJM (2025)
• Article on webpage

Current treatment guidelines for provoked VTE (i.e., VTE after immobilization, surgery, extended travel, or pregnancy) recommend three months of anticoagulation. Anticoagulation beyond three months (extended anticoagulation) is typically reserved for patients with strong, persistent VTE risk factors, including active cancer or thrombophilia. The effects of extended anticoagulation on patients with provoked VTE who have minor chronic VTE risk factors (e.g., obesity, CVD) are unknown. To explore this clinical gap, researchers performed the HI-PRO trial, where 600 adults with provoked VTE and minor chronic VTE risk factors were randomized to 12 months of apixaban (2.5 mg twice daily) or placebo after completing at least 3 months of anticoagulation. The prevalence of minor risk factors and results after one year were as follows:

• Chronic VTE risk factors: Chronic inflammatory or autoimmune disorder - 52%, Obesity - 48%, CVD - 29%, Chronic lung disease - 22%, Chronic kidney disease - 11%
• Symptomatic recurrent VTE: Apixaban - 1.3%, Placebo - 10% (P<0.001)
• Major bleeding: Apixaban - 0.3%, Placebo - 0% (P>0.999)

In the HI-PRO trial, extended anticoagulation was superior to three months of anticoagulation in patients with provoked VTE who had minor chronic risk factors for recurrence (55% of participants had two or more risk factors). The first-year VTE recurrence rate in the placebo group was 10%, which is notably higher than the 1–6% rate observed in other studies enrolling patients with provoked VTE. The unexpectedly high placebo recurrence rate and the resulting clinical benefit from extended anticoagulation suggest that current risk stratification models may underestimate the impact of less significant chronic risk factors (e.g., chronic inflammatory disorders, CVD, obesity) when determining the need for indefinite anticoagulation following a provoked VTE. One limitation of the study is the 12-month treatment duration, which may not reflect the full risks and benefits of lifelong anticoagulation. It will be interesting to see how future guidelines incorporate data from this study. In the interim, providers may consider discussing the implications of this study with patients who present with provoked VTE and coexisting minor, long-term risk factors for recurrence.

• Extended Anticoagulation vs Standard Duration (3 months) after Provoked VTE, NEJM (2025)
• Article on webpage

Catheter ablation has become a common treatment for atrial fibrillation (AF), and many patients undergo the procedure in hopes of stopping anticoagulation. Catheter ablation success, defined as no atrial arrhythmias, depends on the type of AF and the length of follow-up. One-year success rates for paroxysmal AF are 70% to 85%, while persistent AF has a success rate of 50% to 70%. Over longer follow-up periods, success rates decline. Since catheter ablation is not 100% curative, and AF can come and go without symptoms, stopping anticoagulation after the procedure may increase stroke risk. Conversely, continuing anticoagulation increases bleeding risk. To examine the issue, researchers performed the ALONE-AF trial, where 840 patients (median CHA2DS2-VASc score of 2) with AF who had undergone catheter ablation and had no documented AF recurrence for at least one year were randomized to continuing anticoagulation (with apixaban or rivaroxaban) or stopping it. No atrial arrhythmia recurrence was documented with ECGs and at least two sessions of 24- to 72-hour Holter monitoring, with at least one performed within two months of enrollment. After two years, the primary outcome, a composite of stroke, systemic embolism, and major bleeding, was observed in 0.3% of the discontinue group and 2.2% of the continue group (P=0.02). Stroke was seen in 0.3% and 1.4%, respectively, and major bleeding in 0% and 1.4% (P=0.03).

Prior to this study, providers had limited data on the risks and benefits of stopping anticoagulation after ablation. The criteria used in the study for documenting no AF recurrence (at least two sessions of 24- to 72-hour Holter monitoring without atrial arrhythmia) serve as a starting point for selecting patients for anticoagulant discontinuation. Most patients in the study had paroxysmal AF (68%), which is more responsive to ablation. Although the study did not find differences in outcomes for patients with persistent AF, this subgroup was underrepresented.

• ALONE-AF Study: Discontinue vs Continue anticoagulation after ablation, JAMA (2025)
• Article on webpage

Animal-derived thyroid products, including Armour Thyroid, NP Thyroid, WP Thyroid, and Nature-throid, are not FDA-approved to treat hypothyroidism; however, they existed before the Food, Drug, and Cosmetic Act of 1938 and, therefore, were grandfathered into the FDA's list of prescription drug medications without going through the formal approval process. The products are produced from dried, ground thyroid glands, typically from pigs. The FDA contends that due to a lack of safety and efficacy data, these products may be unsafe because of variations in purity and potency and the presence of contaminants. The agency sent letters to manufacturers on August 6, 2025, notifying them of their intent to take action against unapproved animal-derived thyroid medications. The FDA is also encouraging healthcare providers to transition patients from animal-derived products to synthetic levothyroxine.

An estimated 1.5 million Americans receive prescriptions for animal-derived combination products each year. However, all major professional organizations recommend synthetic levothyroxine products (e.g., Synthroid) for treating hypothyroidism. Reasons they are preferred over combination products include:

• Combination products (e.g. Armour Thyroid) have a T4 to T3 ratio of 4:1, while physiologic ratios secreted by the thyroid gland are around 14:1.
• Combination therapy leads to supraphysiologic levels of T3, which may lead to symptoms of thyrotoxicosis
• T3 has a shorter half-life than T4, which can lead to fluctuations in T3 levels, with a peak occurring shortly after dosing
• There is substantially more data from trials on the use of levothyroxine compared to combination therapy

In my experience, patients who are on animal-derived combination products have already tried synthetic levothyroxine and feel that the combination products control their symptoms better. However, blinded studies comparing levothyroxine to combination products have not found a difference in symptom control. Despite this, it can be difficult to change patient perceptions, especially with regard to subjective symptoms. I anticipate significant pushback when trying to switch these patients to levothyroxine products.

• FDA notification on animal-derived thyroid products
• Hypothyroidism review
• Evaluating the effectiveness of combined T4 and T3 therapy or desiccated thyroid versus T4 monotherapy in hypothyroidism: a systematic review and meta-analysis, BMC Endocr Disord (2024)
• Article on webpage

In 2021, the SGLT2 inhibitor empagliflozin (Jardiance) became the first drug FDA-approved to treat heart failure with preserved ejection fraction (HFpEF). Several years later, another SGLT2 inhibitor, dapagliflozin (Farxiga), was approved. Now, Finerenone (Kerendia), a nonsteroidal mineralocorticoid receptor antagonist, has become the third drug and the first non-SGLT2 inhibitor to be approved. Approval was based on results from the FINEARTS-HF Study, where 6016 patients with heart failure and an ejection fraction (EF) of 40% or greater (average EF 53%) were randomized to finerenone or placebo. Over a median follow-up of 32 months, the incidence of the primary composite outcome (total worsening heart failure events and death from cardiovascular causes) was 14.9 events per 100 patient-years in the finerenone group and 17.7 events per 100 patient-years in the placebo group (P=0.007). There was no significant difference in overall mortality. Hyperkalemia was more common in the finerenone group (14.3% vs 6.9%) as was hypotension (18.5% vs 12.4%).

Finerenone blocks aldosterone receptors, similar to spironolactone, an inexpensive aldosterone antagonist that has been available for decades. Spironolactone, which is FDA-approved for heart failure with reduced ejection fraction (HFrEF), has also been studied in HFpEF. In the TOPCAT study, which enrolled 3445 patients with heart failure and an EF ≥ 45% (median EF 56%), spironolactone was not superior to placebo for a composite of CVD events; however, it did significantly reduce heart failure hospitalizations. The trial was plagued by discordant data in certain geographic regions (Russia, Georgia), and post-hoc analyses have found that when these regions were excluded, spironolactone significantly improved the primary outcome. The ACC 2023 HFpEF guidelines recommend spironolactone in some patients. Other drugs, including Entresto, Wegovy, and Zepbound, have demonstrated improvements in HFpEF outcomes in clinical trials but have not received FDA approval for the condition.

Finerenone is the third drug and only non-SGLT2 inhibitor approved for HFpEF. Providers should note that finerenone dosing recommendations for HFpEF, which are based on GFR and potassium levels, differ from those used in diabetic kidney disease. For patients who cannot afford finerenone, spironolactone likely offers similar benefits. Potassium levels should be monitored closely with either drug.

• Finerenone review
• HFpEF treatment recommendations
• Article on webpage