Practice Changing Updates

INTRODUCTION — 

This section highlights selected specific new recommendations and/or updates that we anticipate may change usual clinical practice. Practice Changing Updates focus on changes that may have significant and broad impact on practice, and therefore do not represent all updates that affect practice. These Practice Changing Updates, reflecting important changes to UpToDate over the past year, are presented chronologically, and are discussed in greater detail in the identified topic reviews.

NEPHROLOGY AND HYPERTENSION (June 2026)

A trial of finerenone in nondiabetic chronic kidney disease

●In patients with nondiabetic chronic kidney disease (CKD) who, despite treatment with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) plus an sodium-glucose cotransporter 2 (SGLT-2) inhibitor, have a urine albumin-to-creatinine ratio ≥200 mg/g (or measured albumin excretion ≥200 mg/day), estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73 m², and a serum potassium ≤4.8 mEq/L, we suggest addition of finerenone (Grade 2B).

Finerenone has been shown to improve kidney and cardiovascular outcomes in patients with diabetic kidney disease and albuminuria. The effect of this agent in nondiabetic chronic kidney disease (CKD) was examined in a trial in which nearly 1600 patients who had estimated glomerular filtration rate (eGFR) 25 to <90 mL/min/1.73m2 and urine albumin-to-creatinine ratio 200 to 3500 mg/g were randomly assigned to finerenone or placebo [1]. At three years, the rates of a composite kidney outcome (ie, a 57 percent reduction in eGFR or kidney failure) and of a composite cardiovascular outcome (ie, hospitalization for heart failure or cardiovascular death) were lower with finerenone, although these findings were not statistically significant. Given these findings and extrapolating from those in patients with diabetic kidney disease, we now suggest finerenone in patients with nondiabetic CKD who continue to have albuminuria despite standard treatments. (See "Overview of the management of chronic kidney disease in adults", section on 'Patients with albuminuria'.)

INFECTIOUS DISEASES (May 2026)

Ensitrelvir for post-exposure prophylaxis after household COVID-19 exposure

●For individuals with risk factors for severe COVID-19, we suggest ensitrelvir prophylaxis following household exposure (Grade 2B).

Ensitrelvir is a protease inhibitor with antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In a randomized trial of over 2000 individuals who had a household exposure to SARS-CoV-2, starting a five-day course of ensitrelvir within 72 hours reduced the incidence of coronavirus disease 2019 (COVID-19) by approximately 67 percent compared with placebo (2.9 versus 9 percent) [2]. Ensitrelvir was well tolerated, associated only with a transient decrease in high-density lipoprotein levels. Based on these data, we suggest ensitrelvir for individuals at high risk for severe COVID-19 (such as age ≥65 years, medical comorbidities, and immunocompromising conditions) following household or similarly close contact with a person with confirmed infection; ensitrelvir should be started as soon as possible and within 72 hours of exposure. The drug is available in Japan and was recently approved by the US Food and Drug Administration. (See "COVID-19: Epidemiology, virology, and prevention", section on 'Postexposure prophylaxis'.)

OBSTETRICS, GYNECOLOGY AND WOMEN'S HEALTH (May 2026, Modified May 2026)

Updated guidance for patients with postmenopausal vaginal bleeding

●For most patients with postmenopausal bleeding, we perform both endometrial sampling and transvaginal ultrasound for initial evaluation of the endometrium.

Patients with postmenopausal vaginal bleeding require evaluation of the endometrium for endometrial cancer and premalignant lesions. The American College of Obstetricians and Gynecologists (ACOG) recently updated its guidance for the evaluation of the endometrium in such patients [3]. Previously, they permitted transvaginal ultrasound (TVUS) as an alternative to endometrial sampling in most patients with an endometrial thickness <4 mm. However, due to rising rates of endometrial cancer, the potential for a false negative result on TVUS, and the tendency for high-risk endometrial cancers to present with thinner linings, ACOG now recommends that both endometrial sampling and TVUS, with few exceptions. We follow this updated guidance and counsel most patients with postmenopausal bleeding to have endometrial sampling and TVUS. (See "Overview of the evaluation of the endometrium for malignant or premalignant disease", section on 'Postmenopausal patients with bleeding'.)

INFECTIOUS DISEASES (February 2026)

Updated recommendations for individuals with chronic hepatitis B virus infection

●For persons with chronic hepatitis B virus (HBV) infection in the immune-tolerant phase (hepatitis B e antigen [HBeAg]-positive, markedly elevated HBV DNA, normal alanine aminotransferase) who are at high risk for cirrhosis or hepatocellular carcinoma, we suggest antiviral therapy (Grade 2C).

For people without cirrhosis, the decision to treat chronic hepatitis B virus (HBV) infection is based primarily on the alanine aminotransferase (ALT) and HBV DNA levels (table 1). The American Association for the Study of Liver Diseases (AASLD) guidelines for managing chronic HBV infection were recently updated [4]. As before, they recommend antiviral treatment for patients without cirrhosis in the immune-active phase (elevated ALT and HBV DNA) (table 2). They now also suggest treatment for those in the immune-tolerant phase (hepatitis B e antigen [HBeAg]-positive, normal ALT, markedly elevated HBV DNA) who are at high risk for cirrhosis or hepatocellular carcinoma; risks include age >40 years, ≥F2 fibrosis, and ≥grade 2 inflammation. Although not well studied in this population, antiviral therapy is likely to reduce the risk of these adverse outcomes. For most other patients without cirrhosis, we use shared decision-making to guide treatment. (See "Hepatitis B virus infection: Overview of management", section on 'Determining need for antiviral therapy'.)

ONCOLOGY (February 2026)

Palbociclib maintenance for advanced hormone receptor-positive, HER2-positive breast cancer

●For patients with advanced hormone receptor-positive, HER2-positive cancers without progression after induction chemotherapy, we suggest the addition of palbociclib to maintenance therapy with endocrine therapy and anti-HER2 therapy (Grade 2B), although reserving it for a later line of therapy is an acceptable alternative.

For patients with advanced hormone receptor-positive, HER2-positive cancers, initial treatment often involves taxane-containing chemotherapy plus trastuzumab and pertuzumab (THP) as induction treatment followed by maintenance therapy with endocrine therapy and anti-HER2 therapy. In a randomized trial in 518 such patients, addition of palbociclib to endocrine therapy and anti-HER2 therapy maintenance improved median progression-free survival (44 versus 29 months), but with added toxicity, primarily neutropenia and leukopenia [5]. Overall survival data remain immature. Based on these data, for hormone receptor-positive, HER2-positive cancers treated with THP induction, we suggest the addition of palbociclib to maintenance with endocrine therapy and anti-HER2 therapy. (See "Systemic treatment for HER2-positive metastatic breast cancer", section on 'Chemotherapy induction with endocrine therapy maintenance for hormone receptor-positive cancers'.)

PULMONARY AND CRITICAL CARE MEDICINE (January 2026)

Nerandomilast for treatment of progressive pulmonary fibrosis

●For patients with non-idiopathic pulmonary fibrosis interstitial lung disease (ILD) who develop progressive pulmonary fibrosis despite optimal initial ILD management, we suggest treatment with nintedanib or nerandomilast (Grade 2B). For patients with continued progression despite one of these agents, we suggest combination therapy with the two agents as tolerated (Grade 2C).

Nerandomilast is an oral phosphodiesterase 4B inhibitor with antifibrotic and immunomodulatory properties recently approved for the treatment of progressive pulmonary fibrosis [6]. Nerandomilast does not require monitoring of liver function and can be used in those with moderate kidney or liver disease. In one clinical trial that included patients on background nintedanib, nerandomilast use was associated with a 40 to 50 percent reduction in forced vital capacity (FVC) decline at 52 weeks compared with placebo [7]. In subgroup analyses, the FVC reduction was similar in size regardless of dose or background nintedanib therapy. All-cause mortality assessed at the end of the trial (up to 114 weeks) also showed a benefit for both the 9 mg and the 18 mg doses [6]. Diarrhea was the most common adverse event, occurring in 15 to 25 percent of patients without background nintedanib and in nearly 50 percent of patients on concomitant nintedanib therapy. Based on these data, we suggest the use of either nerandomilast or nintedanib for those with non-idiopathic progressive pulmonary fibrosis, as well as combination therapy as tolerated in those who continue to progress despite a single agent. (See "Overview of the management of adults with interstitial lung disease", section on 'Progressive pulmonary fibrosis'.)

CARDIOVASCULAR MEDICINE (November 2025)

Long-term antiplatelet therapy after percutaneous coronary intervention in patients taking oral anticoagulation

●For most patients on long-term oral anticoagulant therapy, we now suggest not continuing antiplatelet therapy indefinitely (Grade 2B), and typically stop 6 to 12 months after percutaneous coronary intervention. However, for selected patients who are at very high risk of thrombotic events, it is reasonable to continue a single antiplatelet drug.

Patients with an indication for oral anticoagulation (OAC) who undergo percutaneous coronary intervention (PCI) often receive combination antithrombotic therapy (ie, OAC plus an antiplatelet medication) indefinitely; however, it is uncertain whether long-term antiplatelet therapy is necessary. Two recent trials addressed this question:

•A trial in over 800 patients with stent placement >6 months prior to enrollment and current treatment with long-term OAC found that participants randomly assigned to aspirin had higher rates of death and major bleeding compared with those assigned to placebo [8].

•A trial in over 900 patients with stent placement >12 months prior to enrollment found that patients randomly assigned to direct oral anticoagulant (DOAC) monotherapy had lower rates of a composite endpoint of death, myocardial infarction, stent thrombosis, stroke, systemic embolism, and clinically important bleeding compared with those assigned to combination therapy (DOAC plus clopidogrel); this difference was driven primarily by a reduction in bleeding [9].

For most patients on long-term OAC, we now suggest not continuing antiplatelet therapy indefinitely, and typically stop 6 to 12 months after PCI. However, for selected patients at very high risk of thrombotic events, it is reasonable to continue a single antiplatelet drug. (See "Coronary artery disease patients requiring combined anticoagulant and antiplatelet therapy", section on 'Long-term therapy studies'.)

NEPHROLOGY AND HYPERTENSION (November 2025)

Fish oil supplements for patients on maintenance dialysis

●For patients on maintenance dialysis, we suggest fish oil supplements (Grade 2B) to prevent new and recurrent cardiovascular events. However, future trials to confirm benefit are warranted.

Patients on dialysis are at high risk of cardiovascular (CV) morbidity and mortality. In a trial in which over 1200 patients on maintenance hemodialysis were randomly assigned to either high-dose fish oil supplementation or placebo, the rate of serious CV events (ie, CV death, nonfatal myocardial infarction, nonfatal stroke, and peripheral vascular disease leading to amputation) was lower in the fish oil group during 3.5 years of follow-up (0.31 versus 0.61 per 1000 patient-days) [10]. The benefit in patients without a history of CV disease (approximately two-thirds of the study population) was similar to that in patients with such a history. However, fish oil did not lead to a statistically significant reduction in all-cause mortality. Based on these data, we now suggest fish oil supplements for patients on maintenance dialysis. (See "Secondary prevention of cardiovascular disease in end-stage kidney disease (dialysis)", section on 'Fish oil'.)

PRIMARY CARE (ADULT) (October 2025)

Clopidogrel versus aspirin for secondary prevention of chronic coronary disease

●For patients with chronic coronary disease who have not had acute coronary syndrome or percutaneous coronary intervention in the past 12 months, we suggest long-term antiplatelet therapy with clopidogrel (Grade 2C). Aspirin is a reasonable alternative.

Aspirin has traditionally been the mainstay of antiplatelet therapy for the long-term secondary prevention of cardiovascular disease. However, in a meta-analysis of seven randomized trials that included almost 29,000 patients with established coronary artery disease, rates of major adverse cardiovascular or cerebrovascular events were lower in those receiving clopidogrel than in those receiving aspirin (2.61 versus 2.99 per 100 patient-years) at 5.5 years of follow-up [11]. Both groups experienced similar rates of major bleeding, cardiovascular death, and all-cause mortality. Although most participants had presented with acute coronary syndrome (ACS) and undergone percutaneous coronary intervention (PCI), approximately 25 percent were managed with medical therapy alone. Based on these findings, we now suggest long-term antiplatelet therapy with clopidogrel in patients with chronic coronary disease who have not had ACS or PCI in the past 12 months; aspirin remains a reasonable alternative. (See "Aspirin and antiplatelet therapy for the secondary prevention of atherosclerotic cardiovascular disease", section on 'Patients with chronic ASCVD'.)

GASTROENTEROLOGY AND HEPATOLOGY (August 2025, Modified September 2025)

Semaglutide in metabolic dysfunction-associated steatohepatitis

●For patients with metabolic dysfunction-associated steatohepatitis (MASH) and stage ≥2 fibrosis who do not achieve their weight loss goals with lifestyle interventions alone, we suggest GLP-1-based therapy for treatment of MASH (Grade 2C).

Glucagon-like peptide-1 (GLP-1)-based therapies are widely used to treat obesity, and they improve liver inflammation in metabolic dysfunction-associated steatohepatitis (MASH). New data show that a GLP-1 receptor agonist can also improve fibrosis [12]. In an interim analysis of a randomized controlled trial including 800 patients with MASH and stage 2 or 3 fibrosis, the GLP-1 agonist semaglutide for 72 weeks improved liver fibrosis compared with placebo (37 versus 22 percent) and resolved steatohepatitis. These data support our suggestion to use GLP-1-based therapies in patients with MASH. In August 2025, the US Food and Drug Administration approved semaglutide for treatment of MASH [13]. (See "Management of metabolic dysfunction-associated steatotic liver disease (nonalcoholic fatty liver disease) in adults", section on 'GLP-1-based therapies'.)

PULMONARY AND CRITICAL CARE MEDICINE (September 2025)

Brensocatib for bronchiectasis with frequent exacerbations

●For patients with bronchiectasis who have two or more exacerbations in a year despite a trial of antibiotic therapy (eg, macrolide, antipseudomonal inhaled antibiotic), or for those who cannot tolerate ongoing antibiotic therapy, we suggest the addition of brensocatib (Grade 2B).

Brensocatib is a new oral therapy for bronchiectasis that inhibits activation of neutrophil elastases. In a new randomized trial in which 1721 patients with at least two bronchiectasis exacerbations in the prior year were assigned to brensocatib 10 mg or 25 mg daily or placebo for 52 weeks, brensocatib (either dose) reduced annual exacerbation rates by 20 percent and increased the proportion of patients who remained exacerbation-free (48.5 versus 40 percent) [14]. Brensocatib was well tolerated, with mild to moderate hyperkeratosis as the most frequent side effect, occurring in 1.4 to 3 percent of patients. Brensocatib was approved in the United States for non-cystic fibrosis bronchiectasis in individuals >12 years. We suggest brensocatib as add-on therapy in those who continue to have exacerbations despite a macrolide or inhaled antipseudomonal antibiotic. (See "Bronchiectasis in adults: Maintaining lung health", section on 'Elastase inhibitors'.)

ONCOLOGY (August 2025, Modified September 2025)

Aspirin for stage I to III PIK3CA-mutated colorectal cancer

●For patients with stage I to III colorectal cancer and a somatic (tumoral) phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation who have completed surgery, we suggest aspirin (Grade 2C), at a dose of 160 mg orally daily, to be continued for three years.

For patients with treated stage I to III colorectal cancer (CRC) and a somatic (tumoral) phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)mutation, studies are evaluating the benefits of aspirin. In a placebo-controlled randomized trial of over 600 patients with stage I to III PIK3CA-mutated colorectal cancer who completed surgery, low-dose aspirin (160 mg daily) for three years reduced the recurrence rate (hazard ratio 0.45; 8 versus 14 percent for those with PIK3CA mutations in exon 9 or 20) [15]. Among those with other PI3K pathway alterations, it reduced recurrence rates (8 versus 17 percent) and improved three-year disease-free survival (89 versus 79 percent). For patients with stage I to III CRC who complete surgery and have a somatic PIK3CA mutation, we now suggest low-dose aspirin, to be continued for three years. (See "Adjunctive therapy for non-metastatic treated colorectal cancer: Aspirin, NSAIDs, and vitamin D", section on 'PIK3CA mutations'.)

INFECTIOUS DISEASES (May 2025, Modified August 2025)

Chikungunya vaccination in travelers

●When chikungunya vaccination is indicated, we recommend recombinant virus-like particle over live-attenuated virus vaccine because of potential safety signals of the live-attenuated virus vaccine (Grade 1C).

Chikungunya virus is a growing public health concern; travelers frequently acquire infection and can import the virus into new areas. Apart from avoiding mosquito exposure, vaccination is the primary preventive strategy:

•In 2025, the US Food and Drug Administration (FDA) approved and the Centers for Disease Control and Prevention (CDC) recommended recombinant virus-like particle (VLP) chikungunya vaccine (VIMKUNYA) for selected high-risk travelers aged 12 years and older [16,17]; approval was based on several trials demonstrating high seroconversion rates.

•Reports of serious adverse effects in older adults following receipt of the previously approved live-attenuated virus chikungunya vaccine (IXCHIQ) prompted several regulatory agencies to restrict use in older adults or advise caution [18,19]. In the United States, the FDA withdrew approval of the live-attenuated virus chikungunya vaccine [20].

When indicated, we recommend the recombinant VLP over the live-attenuated virus vaccine; if the recombinant VLP vaccine is unavailable, the live-attenuated virus vaccine may be used in immunocompetent adults <60 years old. (See "Chikungunya fever: Treatment and prevention", section on 'Indication and choice of vaccine'.)

INFECTIOUS DISEASES (July 2025)

Updated guidelines for prophylaxis after a nonoccupational exposure to HIV

●For most people who initiate nonoccupational post-exposure prophylaxis to prevent HIV, we suggest bictegravir-emtricitabine-tenofovir alafenamide (Grade 2C).

People who present within 72 hours of a possible nonoccupational exposure to human immunodeficiency virus (HIV) should be evaluated for post-exposure prophylaxis with antiretroviral therapy (nPEP). If indicated, updated guidelines from the United States Centers for Disease Control and Prevention suggest bictegravir-emtricitabine-tenofovir alafenamide or dolutegravir plus either tenofovir alafenamide or tenofovir disoproxil fumarate [21]. Previously, tenofovir alafenamide had been avoided for nPEP, particularly for exposure through vaginal sex, but emerging indirect data from pre-exposure prophylaxis trials support its use. For most people, we suggest bictegravir-emtricitabine-tenofovir alafenamide since it is administered as a single pill once daily. There may be additional considerations for regimen selection in those with reduced kidney function or exposure to drug-resistant HIV. (See "Management of nonoccupational exposures to HIV and hepatitis B and C in adults", section on 'Preferred regimens'.)