Top 20 Research Studies of 2025 for Primary Care Physicians

Mark H. Ebell, MD, MS
Roland Grad, MD, MSc

American Family Physician. 2026;114(2):175-183.

Author Disclosure: Dr. Ebell is the cofounder and editor-in-chief of Essential Evidence Plus; see Editor's Note.

This clinical content conforms to AAFP criteria for CME.

This article summarizes the top 20 research studies of 2025 identified as POEMs (patient-oriented evidence that matters). Treating male sex partners of female patients with oral and topical medication reduces recurrence of bacterial vaginosis. Anti-influenza drugs do not reduce hospitalizations or mortality. COVID-19 vaccines still improve mortality and reduce hospitalizations. Influenza vaccines are safe in pregnancy. Vaginal estrogen appears to be safe in breast cancer survivors. Women with normal bone density given zoledronic acid every 5 years have fewer fractures. Early post-partum insertion of a long-acting reversible contraceptive is associated with fewer pregnancies vs delayed insertion. Early medication abortion before pregnancy confirmation is safe and effective. After stent placement in patients with atherosclerotic coronary vascular disease who are taking an anticoagulant, adding aspirin worsens outcomes. After catheter ablation for atrial fibrillation, discontinuing anticoagulants after 1 year is safe if atrial arrhythmia does not recur, whereas left atrial appendage closure is superior to oral anticoagulation. For patients with provoked venous thromboembolism and at least one ongoing risk factor, 12 months of apixaban is better than 3 months. Clopidogrel is slightly more effective than aspirin for the secondary prevention of myocardial infarction and stroke over 3 years. Intensive blood pressure lowering decreases cardiovascular events but increases rates of hypotension and syncope, and there are concerns about the applicability of the data to the United States. Duloxetine, milnacipran, and pregabalin provide meaningful pain reduction in adults with fibromyalgia. Amyloid-directed monoclonal antibodies do not provide clinically meaningful cognitive benefits and may cause harms. Bright light therapy is effective for nonseasonal depression. Water exposure 6 hours after cutaneous surgery does not increase the risk of complications. A meta-analysis of platelet-rich plasma injections for knee osteoarthritis concluded that high-quality studies found no meaningful pain improvement. Using an oral challenge to rule out sulfonamide allergy is safe when used with a risk assessment tool.

For more than 25 years, a team of six clinicians has reviewed more than 100 clinical medical journals monthly to identify studies that are most likely to change primary care practice for the better. The team includes experts in family medicine, pharmacy, hospital medicine, and women's health.

The goal of this process is to identify POEMs (patient-oriented evidence that matters). To qualify as a POEM, the study should report at least one patient-oriented outcome, defined as improvement in outcomes that matter to patients, such as morbidity, mortality, symptoms, or quality of life. This contrasts with disease-oriented evidence, which describes results such as changes in laboratory values, imaging studies, or other parameters that do not inherently reflect patient-oriented improvements. The study should be free of biases that threaten the validity of the results.1,2 The word “matters” in POEM also means that the results would change what many primary care physicians do by encouraging the adoption of a new practice or discontinuing an old one. Each year, more than 20,000 research studies are reviewed by the POEMs team, but in 2025, only 260 met the inclusion criteria. All new POEMs are emailed to subscribers of Essential Evidence Plus (Wiley-Blackwell, Inc), and a selection appears in American Family Physician (AFP).

MARK H. EBELL, MD, MS, is a professor in the Department of Family Medicine at Michigan State University, East Lansing.

ROLAND GRAD, MD, MSc, is an associate professor at McGill University, Montreal, Quebec, Canada.

Dr. Grad has no relevant financial relationships.

Published online July 13, 2026.

Address correspondence to Mark H. Ebell, MD, MS, at ebell@msu.edu.

Author Disclosure: Dr. Ebell is the cofounder and editor-in-chief of Essential Evidence Plus; see Editor's Note.

  1. 1.Slawson DC, Shaughnessy AF, Bennett JH. Becoming a medical information master: feeling good about not knowing everything. J Fam Pract. 1994;38(5):505-513.
  2. 2.Ebell MH, Barry HC, Slawson DC, et al. Finding POEMs in the medical literature. J Fam Pract. 1999;48(5):350-355.
  3. 3.Vodstrcil LA, Plummer EL, Fairley CK, et al.; StepUp Team. Male-partner treatment to prevent recurrence of bacterial vaginosis. N Engl J Med. 2025;392(10):947-957.
  4. 4.Gao Y, Zhao Y, Liu M, et al. Antiviral medications for treatment of nonsevere influenza: a systematic review and network meta-analysis. JAMA Intern Med. 2025;185(3):293-301.
  5. 5.Cai M, Xie Y, Al-Aly Z. Association of 2024–2025 covid-19 vaccine with covid-19 outcomes in U.S. veterans. N Engl J Med. 2025;393(16):1612-1623.
  6. 6.Jefferson T, Jones MA, Doshi P, et al. Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children. Cochrane Database Syst Rev. 2012(1):CD008965.
  7. 7.Ebell MH, Call M, Shinholser J. Effectiveness of oseltamivir in adults: a meta-analysis of published and unpublished clinical trials. Fam Pract. 2013;30(2):125-133.
  8. 8.Centers for Disease Control and Prevention. Preliminary estimates of COVID-19 burden. Accessed February 6, 2026. https://www.cdc.gov/covid/php/surveillance/burden-estimates.html
  9. 9.Lee H, Yoon D, Kim JH, et al. Association of influenza vaccination during pregnancy with health outcomes in mothers and children: a population-based cohort study. Clin Pharmacol Ther. 2025;117(5):1381-1392.
  10. 10.Bolland MJ, Nisa Z, Mellar A, et al. Fracture prevention with infrequent zoledronate in women 50 to 60 years of age. N Engl J Med. 2025;392(3):239-248.
  11. 11.Beste ME, Kaunitz AM, McKinney JA, et al. Vaginal estrogen use in breast cancer survivors: a systematic review and meta-analysis of recurrence and mortality risks. Am J Obstet Gynecol. 2025;232(3):262-270.e1.
  12. 12.Provinciatto H, Meirelles Dias YJ, Abonizio Magdalena SL, et al. Immediate vs delayed postpartum insertion of long-acting reversible contraception methods: meta-analysis of randomized controlled trials. Am J Obstet Gynecol. 2025;232(2):139-149.e16.
  13. 13.Brandell K, Jar-Allah T, Reynolds-Wright J, et al.; VEMA (Very Early Medication Abortion) Study Group. Randomized trial of very early medication abortion. N Engl J Med. 2024;391(18):1685-1695.
  14. 14.Lemesle G, Didier R, Steg PG, et al.; AQUATIC Trial Investigators. Aspirin in patients with chronic coronary syndrome receiving oral anticoagulation. N Engl J Med. 2025;393(16):1578-1588.
  15. 15.Kim D, Shim J, Choi EK, et al.; ALONE-AF Investigators. Long-term anticoagulation discontinuation after catheter ablation for atrial fibrillation: the ALONE-AF randomized clinical trial. JAMA. 2025;334(14):1246-1254.
  16. 16.Wazni OM, Saliba WI, Nair DG, et al.; OPTION Trial Investigators. Left atrial appendage closure after ablation for atrial fibrillation. N Engl J Med. 2025;392(13):1277-1287.
  17. 17.Piazza G, Bikdeli B, Pandey AK, et al.; HI-PRO Trial Investigators. Apixaban for extended treatment of provoked venous thromboembolism. N Engl J Med. 2025;393(12):1166-1176.
  18. 18.Valgimigli M, Choi KH, Giacoppo D, et al. Clopidogrel versus aspirin for secondary prevention of coronary artery disease: a systematic review and individual patient data meta-analysis. Lancet. 2025;406(10508):1091-1102.
  19. 19.Guo X, Sun G, Xu Y, et al.; BPRULE Study Group. Benefit-harm trade-offs of intensive blood pressure control versus standard blood pressure control on cardiovascular and renal outcomes: an individual participant data analysis of randomised controlled trials. Lancet. 2025;406(10507):1009-1019.
  20. 20.Boston Scientific. The WATCHMAN implant procedure. Accessed July 3, 2026. https://www.watchman.com/en-us/how-watchman-device-works/watchman-device-procedure.html
  21. 21.Cho MS, Kang DY, Ahn JM, et al.; EPIC-CAD Investigators. Edoxaban antithrombotic therapy for atrial fibrillation and stable coronary artery disease. N Engl J Med. 2024;391(22):2075-2086.
  22. 22.Ebell MH, Slawson DC. BP target should be a shared decision that balances benefits and harms. Am Fam Physician. 2025;112(6):598-599.
  23. 23.Moore A, Bidonde J, Fisher E, et al. Effectiveness of pharmacological therapies for fibromyalgia syndrome in adults: an overview of Cochrane Reviews. Rheumatology (Oxford). 2025;64(5):2385-2394.
  24. 24.Tonegawa-Kuji R, Hou Y, Hu B, et al. Efficacy and safety of passive immunotherapies targeting amyloid beta in Alzheimer's disease: a systematic review and meta-analysis. PLoS Med. 2025;22(3):e1004568.
  25. 25.Ebell MH, Barry HC, Baduni K, et al. Clinically important benefits and harms of monoclonal antibodies targeting amyloid for the treatment of Alzheimer disease: a systematic review and meta-analysis. Ann Fam Med. 2024;22(1):50-62.
  26. 26.Menegaz de Almeida A, Aquino de Moraes FC, Cavalcanti Souza ME, et al. Bright light therapy for nonseasonal depressive disorders: a systematic review and meta-analysis. JAMA Psychiatry. 2025;82(1):38-46.
  27. 27.Tuunainen A, Kripke DF, Endo T. Light therapy for non-seasonal depression. Cochrane Database Syst Rev. 2004(2):CD004050.
  28. 28.Bensa A, Previtali D, Sangiorgio A, et al. PRP injections for the treatment of knee osteoarthritis: the improvement is clinically significant and influenced by platelet concentration: response. Am J Sports Med. 2026;54(1):NP6-NP7.
  29. 29.Samaan C, Kim Y, Zhou S, et al. Early postoperative water exposure does not increase complications in cutaneous surgeries: a randomized, investigator-blinded, controlled trial. J Am Acad Dermatol. 2024;91(5):896-903.
  30. 30.Stehlin F, Vogrin S, Mitri E, et al. International validation of the SULF-FAST risk-stratification tool for sulfonamide antibiotic allergy. JAMA Netw Open. 2025;8(7):e2519113.
  31. 31.Agarwal A, Mustafa R, Manja V, et al. Cardiovascular, kidney related, and weight loss effects of therapeutics for type 2 diabetes: a living clinical practice guideline. BMJ. 2025;390:e082071.
  32. 32.Qaseem A, Obley AJ, Shamliyan T, et al.; Clinical Guidelines Committee of the American College of Physicians. Newer pharmacologic treatments in adults with type 2 diabetes: a clinical guideline from the American College of Physicians. Ann Intern Med. 2024;177(5):658-666.
  33. 33.Chaudhuri D, Nei AM, Rochwerg B, et al. 2024 focused update: guidelines on use of corticosteroids in sepsis, acute respiratory distress syndrome, and community-acquired pneumonia. Crit Care Med. 2024;52(5):e219-e233.

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