In this episode, we review key updates from the 2026 ACC-AHA Guidelines on the Management of Dyslipidemia.

Key Concepts

1. The PREVENT ASCVD equation is now recommended to calculate ASCVD risk, with thresholds at 3%, 5%, and 10%. The previous 7.5% threshold for statin treatment is now 5%.
2. In addition to the 10-year ASCVD estimate, clinicians should consider the use of Lp(a), "risk enhancers", and coronary artery calcium (CAC) scans as a "tie breaker" with shared decision-making when the decision to treat is not clear.
3. In addition to LDL goals of < 100, < 70, or < 55 (depending on risk), the new guidelines also suggest non-HDL-C and apoB goals once LDL cholesterol is at goal.
4. Many patients will require non-statin therapies to achieve lipid goals. The recommended non-statin therapies include ezetimibe, PCSK9 mAb, PCSK9-interfering RNA, and bempedoic acid.

References

• Writing Committee Members, Blumenthal RS, Morris PB, et al. 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2026;153(17):e1154-e1276. doi:10.1161/CIR.0000000000001423
• Wiggins BS, Barac A, Benziger CP, et al. 2026 Dyslipidemia Guideline-at-a-Glance. J Am Coll Cardiol. 2026;87(19):2617-2623. doi:10.1016/j.jacc.2026.02.4872
• Superko H, Garrett B. Small Dense LDL: Scientific Background, Clinical Relevance, and Recent Evidence Still a Risk Even with 'Normal' LDL-C Levels. Biomedicines. 2022;10(4):829. Published 2022 Apr 1. doi:10.3390/biomedicines10040829

In this episode, we discuss the most important annual updates in the American Diabetes Association Guidelines, Standards of Care 2026, particularly focusing on changes in pharmacotherapy recommendations and the supporting evidence.

Key Concepts

1. A few existing agents now have ASCVD risk reduction data in patients with existing ASCVD or high indicators for ASCVD. They are: oral semaglutide and tirzepatide.
2. SGLT2is are still first-line in patients with diabetes and HF including HFpEF, but SC semaglutide and tirzepatide are now recommended for those with symptomatic HFpEF and obesity due to positive outcomes in this population.
3. The GLP-1RA and dual GLP-1/GIP RA are the preferred agents for weight management in patients with T2DM, but use of GLP-1RA can be considered for weight loss in patients with T1DM.
4. The guideline also better defines recommendations for medication-induced hyperglycemia from immune checkpoint inhibitors, PI3Kɑ (phosphoinositidylinositol 3-kinase α) inhibitors, mTOR inhibitors, and steroids.

References

• American Diabetes Association. Standards of care in diabetes—2026. Diabetes Care. 2026;49(suppl 1):S1-S377.
• SOUL study. Darren K. McGuire, Marx N, Mulvagh SL, et al. Oral semaglutide and cardiovascular outcomes in high-risk type 2 diabetes. N Engl J Med. 2025;392(20):2001-2012. doi:10.1056/NEJMoa2501006.
• SURPASS-CVOT. Nicholls SJ, Pavo I, Bhatt DL, et al. Cardiovascular outcomes with tirzepatide versus dulaglutide in type 2 diabetes. N Engl J Med. 2025;393(24):2409-2420. doi:10.1056/NEJMoa2505928.
• SUMMIT. Packer M, Zile MR, Kramer CM, et al. Tirzepatide for heart failure with preserved ejection fraction and obesity. N Engl J Med. 2025;392(5):427-437. doi:10.1056/NEJMoa2410027.
• STEP-HFpEF. Kosiborod MN, Abildstrom SZ, Borlaug BA, et al. Semaglutide in patients with heart failure with preserved ejection fraction and obesity. N Engl J Med. 2023;389(12):1069-1084. doi:10.1056/NEJMoa2306963.
• STEP-HFpEF DM. Kosiborod MN, Petrie MC, Borlaug BA, et al. Semaglutide in patients with obesity‑related heart failure and type 2 diabetes. N Engl J Med. 2024;390(15):1394‑1407. doi:10.1056/NEJMoa2313917.

In this episode, we review key updates from the 2026 AHA/ASA Guideline for the Early Management of Patients With Acute Ischemic Stroke, including changes to IV thrombolysis, antiplatelet therapy, endovascular treatment, blood pressure goals, and glycemic goals.

Key Concepts

1. Tenecteplase (TNKase) is now equally preferred to alteplase (Activase) by the 2026 AHA/ASA guidelines. Tenecteplase has several advantages related to administration and the risk of medication errors.
2. IV thrombolysis can be given in selected patients up to 9 hours after stroke symptom onset depending on brain imaging findings. Patients with symptom onset less than 4.5 hours are still eligible for IV thrombolysis regardless of brain imaging findings.
3. IV thrombolysis should not be given for mild, non-disabling stroke symptoms. A "non-disabling" stroke means the symptoms do not impair activities of daily living or ability to return to work.
4. The criteria for dual antiplatelet therapy (DAPT) has been updated. DAPT can be given for NIHSS of 4 or 5 (not just 3 or less) and can be started up to 72 hours after stroke onset (not just within 24 hours).

References

• Prabhakaran S, Gonzalez NR, Zachrison KS, et al. 2026 Guideline for the Early Management of Patients With Acute Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association. Stroke. Published online January 26, 2026. doi:10.1161/STR.0000000000000513

In this episode, we review the clinical presentation, diagnosis, and treatment of uncomplicated urinary tract infections.

Key Concepts

1. Uncomplicated urinary tract infections (UTI) are defined as an infection localized to the bladder without any systemic signs or symptoms of infection in someone who is not immunocompromised, pregnant, catheterized, and has normal urologic anatomy.
2. UTIs are most commonly seen in younger women. E. coli is by far the most common urinary pathogen. Symptoms alone drive most of the diagnosis of UTI; however, urinalysis and urine culture can be helpful in some circumstances.
3. Nitrofurantoin (Macrobid) is recommended for men and women for first-line therapy in most patients. Fosfomycin, Bactrim, pivmecillinam, and certain B-lactams can be considered in certain circumstances. Women are usually treated for 3-5 days and men 5-7 days.
4. Some evidence suggests inferior clinical outcomes for B-lactam; however, the amount of data in general is lacking for B-lactams. Recommended B-lactams (aside from pivmecillinam) include amoxicillin/clavulanate, cephalexin, cefadroxil, cefpodoxime, and cefdinir.

References

1. Nelson Z, Aslan AT, Beahm NP, et al. Guidelines for the Prevention, Diagnosis, and Management of Urinary Tract Infections in Pediatrics and Adults: A WikiGuidelines Group Consensus Statement. JAMA Netw Open. 2024;7(11):e2444495. Published 2024 Nov 4. doi:10.1001/jamanetworkopen.2024.44495
2. Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011;52(5):e103-e120. doi:10.1093/cid/ciq257
3. Kurotschka PK, Gágyor I, Ebell MH. Acute Uncomplicated UTIs in Adults: Rapid Evidence Review. Am Fam Physician. 2024;109(2):167-174.
4. https://www.wikiguidelines.org/

In this episode, we review the pharmacology, indications, adverse effects, and unique drug characteristics of 5-HT3 receptor antagonists such as ondansetron (Zofran) and palonosetron (Aloxi).

Key Concepts

1. There are four 5-HT3 (serotonin subtype 3) receptor antagonists on the market: ondansetron, granisetron, dolasetron, and palonosetron. These have primarily been studied for acute chemotherapy-induced nausea and vomiting (within 24 hours of chemotherapy administration) and for post-operative nausea and vomiting.
2. When used for chemotherapy-induced nausea/vomiting, 5-HT3 receptor antagonists are given prior to chemotherapy (usually 30-60 minutes before) on day #1. They are not given on subsequent days because they are not as effective for delayed nausea and vomiting.
3. Palonosetron has the longest half-life, longer binding affinity to the 5-HT3 receptor, and trends towards having the best efficacy among the 5-HT3 receptor antagonists.
4. 5-HT3 receptor antagonists are associated with QTc prolongation and may cause headache, dizziness, constipation, or diarrhea. Their association with an increased risk of serotonin syndrome is controversial and not supported from a mechanistic perspective.

References

• Simino GP, Marra LP, Andrade EI, et al. Efficacy, safety and effectiveness of ondansetron compared to other serotonin-3 receptor antagonists (5-HT3RAs) used to control chemotherapy-induced nausea and vomiting: systematic review and meta-analysis. Expert Rev Clin Pharmacol. 2016;9(9):1183-1194. doi:10.1080/17512433.2016.1190271
• Tricco AC, Soobiah C, Blondal E, et al. Comparative efficacy of serotonin (5-HT3) receptor antagonists in patients undergoing surgery: a systematic review and network meta-analysis. BMC Med. 2015;13:136. Published 2015 Jun 18. doi:10.1186/s12916-015-0371-y
• Hesketh PJ, Kris MG, Basch E, et al. Antiemetics: ASCO Guideline Update. J Clin Oncol. 2020;38(24):2782-2797. doi:10.1200/JCO.20.01296
• Herrstedt J, Clark-Snow R, Ruhlmann CH, et al. 2023 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting. ESMO Open. 2024;9(2):102195. doi:10.1016/j.esmoop.2023.102195
• Rojas-Fernandez CH. Can 5-HT3 Antagonists Really Contribute to Serotonin Toxicity? A Call for Clarity and Pharmacological Law and Order. Drugs Real World Outcomes. 2014;1(1):3-5. doi:10.1007/s40801-014-0004-3
• Li WS, van der Velden JM, Ganesh V, et al. Prophylaxis of radiation-induced nausea and vomiting: a systematic review and meta-analysis of randomized controlled trials. Ann Palliat Med. 2017;6(2):104-117. doi:10.21037/apm.2016.12.01

In this episode, we review the newly published 2025 ACC/AHA hypertension guidelines.

Key Concepts

1. Instead of the Pooled Cohort Equations (PCE) from 2013, the 2025 hypertension guidelines recommend a new risk equation called PREVENT, which incorporates new risk factors and does not include race as part of the risk calculation.
2. The guidelines recommend starting two antihypertensive medications for initial therapy in stage II hypertension and one antihypertensive medication for stage I hypertension.
3. The guidelines no longer recommend specific first-line therapies for black patients. Instead, all patients without compelling indications should be initiated on a thiazide, ACE inhibitor, ARB, or dihydropyridine calcium channel blocker regardless of race/ethnicity.
4. All patients should have a blood pressure goal of < 130/80 mmHg. Some patients may consider a more stringent goal of < 120/80 if they have diabetes or are at a higher risk of future ASCVD events.

References

• Jones DW, Ferdinand KC, Taler SJ, Johnson HM, Shimbo D, Abdalla M, Altieri MM, Bansal N, Bello NA, Bress AP, Carter J, Cohen JB, Collins KJ, Commodore-Mensah Y, Davis LL, Egan B, Khan SS, Lloyd-Jones DM, Melnyk BM, Mistry EA, Ogunniyi MO, Schott SL, Smith SC Jr, Talbot AW, Vongpatanasin W, Watson KE, Whelton PK, Williamson JD. 2025 AHA/ACC/AANP/AAPA/ABC/ACCP/ACPM/AGS/AMA/ASPC/NMA/PCNA/SGIM Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2025 Aug 14. doi: 10.1161/CIR.0000000000001356. Epub ahead of print. PMID: 40811497.

In this episode, we discuss the evidence, safety, and place in therapy of Journavx® (suzetrigine), a newly approved analgesic with a unique non-opioid mechanism of action and additional considerations for its use.

Key Concepts

1. Suzetrigine is a first in its class NaV1.8 sodium channel blocker approved for short-term (14 days or less) pain relief in adults with moderate-to-severe pain. Unlike opioids, suzetrigine is non-sedating and non-dependence forming.
2. Suzetrigine is taken as a whole pill without cutting, crushing, or chewing following a particular dosing schedule where the first dose is taken on an empty-stomach.
   The most common side effects of suzetrigine include pruritus, muscle spasms, increased CPK, rash, and transient (reversible) eGFR decrease.
3. Suzetrigine goes through CYP3A metabolism and therefore has significant interactions with CYP3A inducers and inhibitors. Use with strong inhibitors and moderate to strong inducers is not recommended. Dose reduction of suzetrigine is required if used with moderate inhibitors of CYP3A.
4. Although not formally adopted in a guideline recommendation, suzetrigine's current place in therapy can be moderate-to-severe acute pain relief in adult patients after NSAIDs/APAP options are exhausted, but before or in place of opioid therapy.

References

• Bertoch T, D'Aunno D, McCoun J, et al. Suzetrigine, a Nonopioid Na V 1.8 Inhibitor for Treatment of Moderate-to-severe Acute Pain: Two Phase 3 Randomized Clinical Trials. Anesthesiology. 2025;142(6):1085-1099. doi:10.1097/ALN.0000000000005460

In this episode, we review the pharmacology, indications, adverse effects, monitoring, and unique drug characteristics of angiotensin receptor blockers (ARBs).

Key Concepts

1. ARBs are equally efficacious as ACE inhibitors when used for hypertension, heart failure with reduced ejection fraction (HFrEF), chronic kidney disease (CKD) with proteinuria, and post-MI care. Some limited evidence suggests that they might be better in reducing albuminuria in patients with diabetes. ARBs are generally better tolerated than ACEi due to a lower risk of angioedema and dry cough.
2. While most ARBs are comparable to each other, small differences exists regarding hepatic metabolism (CYP metabolism for losartan, telmisartan, and azilsartan), degree of blood pressure lowering (generally better with azilsartan, olmesartan, valsartan, and candesartan), and additional pharmacological effects (telmisartan with PPAR-Y agonism, losartan with uricosuric effect).
3. ARBs are contraindicated in pregnancy, those with bilateral renal artery stenosis, and those with previous angioedema to ARBs. The most common adverse effects include hypotension and hyperkalemia, but in rare cases acute renal impairment can also occur.
4. Baseline serum creatinine and potassium should be monitored in patients taking ARBs. After initiation or dose adjustment, blood pressure, serum creatinine, and potassium should be repeated in 1-2 weeks. Signs and symptoms of hypotension as well as angioedema should be monitored throughout the treatment period.