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.

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 [1]. 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 platelet 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 [2]. 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 [3]. (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 therapy 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 class of therapy designed to target neutrophilic inflammation by inhibiting activation of neutrophil elastases. In a phase 3 trial, 1721 patients who had at least two bronchiectasis exacerbations in the prior year were treated with brensocatib 10 mg daily, brensocatib 25 mg daily, or placebo for 52 weeks [4]. Compared with placebo, brensocatib reduced annual exacerbation rates by 20 percent and improved the proportion of patients who remained exacerbation-free during treatment (48.5 versus 40 percent). Overall, brensocatib was well tolerated; mild to moderate hyperkeratosis was the most frequent drug-specific side effect, occurring in 1.5 to 3 percent of patients. Brensocatib now has regulatory approval in the United States for non-cystic fibrosis bronchiectasis in adults and children >age 12 years [5]. We suggest use of this new agent as add-on therapy in those who continue to have exacerbations despite a macrolide or antipseudomonal inhaled 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) [6]. 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 [7,8]; 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 [9,10]. In the United States, the FDA withdrew approval of the live-attenuated virus chikungunya vaccine [11].

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 [12]. 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'.)

PULMONARY AND CRITICAL CARE MEDICINE (June 2025)

Add-on therapy for refractory COPD in patients with peripheral eosinophilia

●For patients with COPD and peripheral eosinophilia (≥300 cells/microL) who have recurrent exacerbations despite triple inhaled therapy, we suggest the addition of dupilumab or mepolizumab rather than other therapies (Grade 2C).

The use of biologics targeting type 2 inflammation in chronic obstructive pulmonary disease (COPD) has demonstrated promise, with approval of dupilumab in 2024 and new approval of mepolizumab for patients with eosinophilia and exacerbations despite inhaled therapies. Mepolizumab approval followed a trial of over 800 patients with COPD, peripheral hypereosinophilia (≥300 cells/microL), and exacerbations despite triple inhaled therapy (long-acting muscarinic antagonist, long-acting beta agonist, and inhaled corticosteroid). Those randomized to treatment with the anti-interleukin 5 monoclonal antibody mepolizumab (100 mg subcutaneously monthly) had a reduction in moderate or severe exacerbations compared with placebo (0.80 versus 1.01 events per year), but no improvements in lung function or respiratory symptoms [13]. Similar patients treated with dupilumab have shown a somewhat larger reduction in exacerbation rates and modest improvements in lung function and symptoms. Absent comparative trials, we now suggest either dupilumab or mepolizumab for patients with COPD and peripheral eosinophilia who have persistent exacerbations despite optimized inhaled therapy (algorithm 1). (See "Management of refractory chronic obstructive pulmonary disease", section on 'Mepolizumab'.)

PULMONARY AND CRITICAL CARE MEDICINE (June 2025)

Methotrexate as initial therapy for symptomatic, moderate-to-severe pulmonary sarcoidosis

●For most symptomatic patients with pulmonary sarcoidosis who have severe lung involvement, worsening radiographic opacities, or increasing pulmonary function impairment, we suggest initial treatment with methotrexate rather than glucocorticoid therapy, observation alone, or other alternative therapies (Grade 2C).

Pulmonary sarcoidosis is usually treated initially with oral glucocorticoids, which have numerous side effects. In a new open-label trial of 138 treatment-naïve patients with pulmonary sarcoidosis and moderate-to-severe symptoms, impaired lung function, or disease progression over the last 12 months, patients randomly assigned to weekly oral methotrexate monotherapy for 24 weeks had similar lung function improvement compared with patients assigned to prednisone (6.2 versus 5.7 percentage point improvement in predicted forced vital capacity) [14]. Methotrexate had a slower onset of action but was associated with less weight gain (1.1 versus 5.0 kg) and similar patient satisfaction by the end of the trial. Based in part on this evidence, we now suggest methotrexate as initial therapy for most patients with moderate-to-severe pulmonary sarcoidosis requiring treatment; concurrent oral glucocorticoids are appropriate for those with rapidly progressing disease. (See "Treatment of pulmonary sarcoidosis: Initial approach", section on 'Efficacy of methotrexate'.)

NEUROLOGY (May 2025)

No benefit of mechanical thrombectomy for acute stroke due to medium vessel occlusion

●For patients with acute ischemic stroke due to a medium vessel occlusion (MeVO; ie, middle cerebral artery beyond the proximal dominant M2 segment, anterior cerebral artery beyond the A1 segment, or posterior cerebral artery beyond the P1 segment), we recommend against routine treatment with mechanical thrombectomy (Grade 1B).

Data from multiple randomized clinical trials have established the benefit of mechanical thrombectomy (MT) for acute ischemic stroke due to large vessel occlusion (LVO). However, there was no high-quality evidence to support the use of MT for patients with acute stroke due to medium vessel occlusion (MeVO), generally defined as the middle cerebral artery beyond the proximal dominant M2 segment, the anterior cerebral artery beyond the A1 segment, and the posterior cerebral artery beyond the P1 segment. This situation has changed with new data from the recent ESCAPE-MeVO and DISTAL trials [15,16]. Both trials failed to demonstrate the benefit of MT for patients with acute ischemic stroke due to MeVO, and the ESCAPE-MeVO trial found that MT increased mortality [15]. Given these data, we recommend against routine treatment with MT for patients with acute ischemic stroke due to a MeVO. Regardless of whether they are candidates for MT, eligible patients should still receive standard treatment with intravenous thrombolysis. (See "Mechanical thrombectomy for acute ischemic stroke", section on 'Medium and distal vessel occlusion'.)

INFECTIOUS DISEASES (May 2025)

Tecovirimat not effective for mpox

●For most immunocompetent patients with mpox, we suggest not using antiviral therapy (Grade 2B). In patients with severe disease (eg, encephalitis, pneumonitis) or highly immunocompromised patients at risk for severe disease, we suggest combination antiviral therapy with tecovirimat and either brincidofovir or cidofovir (Grade 2C).

The antiviral tecovirimat has been used for patients with or at risk for severe mpox based on animal studies and observational studies in humans. However, in a randomized clinical trial of mostly immunocompetent people in Africa with clade 1 mpox infection, there were no differences in time to lesion healing (7 versus 8 days), mortality, or pregnancy outcomes with tecovirimat compared with placebo [17]. Preliminary data from a trial evaluating tecovirimat in patients with clade 2 disease demonstrated similar findings [18]. We now suggest not using antiviral therapy for most immunocompetent patients with mpox. For highly immunocompromised patients and those with severe disease (eg, encephalitis or pneumonitis), we suggest tecovirimat plus another antiviral; although monotherapy with tecovirimat does not appear effective for mpox, its role in combination antiviral therapy has not been evaluated. (See "Treatment and prevention of mpox (formerly monkeypox)", section on 'Tecovirimat'.)

PRIMARY CARE (ADULT) (March 2025)

Male partner treatment to prevent recurrence of bacterial vaginosis

●For male sex partners of female patients with confirmed bacterial vaginosis, we suggest simultaneous dual oral and topical antibiotic treatment rather than no treatment or single-drug treatment (Grade 2C), in order to reduce recurrent infection in female patients.

Treatment of male sex partners to reduce bacterial vaginosis (BV) recurrence in females is an area of ongoing study. In a trial of 150 male-female monogamous couples with confirmed BV in the female, treatment of the male partner for one week with an oral and topical antibiotic (metronidazole tablet and clindamycin cream) in addition to standard antimicrobial treatment of the female patient reduced recurrences at 12 weeks compared with treating the female patient only (35 versus 63 percent; risk difference -2.6 recurrences per person-year) [19]. Based on these results, we now suggest dual topical and oral antimicrobial male partner therapy as an effective strategy to reduce BV recurrence in female patients. (See "Bacterial vaginosis: Initial treatment", section on 'Males'.)

ALLERGY AND IMMUNOLOGY (February 2025)

Egg allergy no longer a concern for any vaccines

●Hen's egg allergy is no longer a reason to withhold yellow fever vaccine or any other vaccine, including influenza, measles, mumps, and rubella (MMR), and rabies.

Some vaccines contain trace amounts of egg protein (table 1), but none contain enough to cause reactions in egg-allergic patients. For the last several years, it has been recommended that patients not be asked about egg allergy prior to receiving influenza vaccine. More recently, data have accumulated to show that egg allergy is similarly not a concern for administration of the yellow fever vaccine. In the largest study to date, 171 children with egg allergy, including 24 percent with a history of anaphylaxis, underwent skin testing with the yellow fever vaccine and then received it regardless of skin test results, with no allergic reactions [20]. Thus, we no longer inquire about egg allergy prior to the administration of any vaccine. Vaccine providers should remain prepared to treat rare allergic reactions that may occur after any vaccine, but no special precautions are necessary for recipients with egg allergy. (See "Allergic reactions to vaccines", section on 'Hen's egg'.)

INFECTIOUS DISEASES (January 2025)

Updated United States guidelines on perinatal HIV transmission

●For infants born to women who have maintained a viral load <50 copies/mL on antiretroviral therapy (ART) from 20 weeks gestation through delivery, we suggest two weeks of prophylaxis with zidovudine (Grade 2C). For infants born to mothers who have viremia (HIV RNA level ≥50 copies/mL, either documented or presumed) at the time of, or in the four weeks prior to delivery, we recommend presumptive therapy with a three-drug antiretroviral regimen (Grade 1B). For all others, we engage in shared decision-making to decide between these two approaches.

The United States Department of Health and Human Services has updated the perinatal HIV clinical guidelines [21]. They now categorize infants born to mothers with HIV into three risk stratification groups based on maternal HIV viral load during pregnancy, the most significant risk factor for transmission. The lowest-risk infants are born to mothers with sustained viral suppression (HIV RNA <50 copies/mL) since 20 weeks gestation. The highest-risk infants are born to mothers with a detectable HIV viral load within four weeks of delivery. All other infants fall into the middle-risk category. This risk stratification informs the antiretroviral regimen given to the infant to prevent HIV transmission, outlined in the table (table 2). Our approach to the management of infants exposed to HIV at birth is consistent with these updated guidelines. (See "Management of infants born to mothers with HIV in resource-abundant settings", section on 'Approach to ARV drug management'.)

INFECTIOUS DISEASES (November 2024)

Lower age cutoff for pneumococcal vaccine indications

●We recommend pneumococcal vaccination for all adults ≥65 years old and adults <65 years old who are at risk for pneumococcal infection or severe complications from pneumococcal infection (Grade 1B). We also suggest pneumococcal vaccination for all adults between 50 to 64 years of age (Grade 2C).

In October 2024, the United States Advisory Committee (ACIP) extended pneumococcal vaccination recommendations to include all adults ≥50 years of age, regardless of risk factors (table 3) [22]. Previously, the age threshold was ≥65 years for healthy adults and ≥19 years for those at risk for pneumococcal infection or severe complications from pneumococcal infection. This decision is based on knowledge that the incidence of pneumococcal disease starts to increase at age 50 (table 4) and the predicted reduction in invasive pneumococcal disease cases in certain underrepresented ethnic/racial groups within the United States. We agree with the new guidelines from the ACIP and now suggest pneumococcal vaccination beginning at age 50 for all adults. (See "Pneumococcal vaccination in adults", section on 'Indications for vaccination'.)