Advances in pharmacotherapy are changing the way hospitalists treat patients, with new drugs offering improved outcomes for various conditions. Niti Patel, MD, PharmD, and Thomas Chen, MD, PharmD, presented a session on emerging pharmacologic therapies that directly impact inpatient medicine.
The session focused on terlipressin, the first U.S. Food and Drug Administration (FDA)-approved medication for use in patients with hepatorenal syndrome (HRS). As a vasopressin analog, terlipressin reduces splanchnic vasodilation and increases renal perfusion.
In the CONFIRM trial, terlipressin plus albumin demonstrated higher rates of HRS reversal than placebo. Other trials indicate that it reduced the need for renal replacement therapy. Compared to midodrine-octreotide, it doubled HRS-acute kidney injury reversal and improved survival outcomes overall.
Major adverse effects are a concern: death due to respiratory failure occurred in 11% of the terlipressin group compared to 2% in the placebo group, so it is generally contraindicated in patients with significant hypoxemia. Patients with serum creatinine greater than 5 mg/dL are unlikely to benefit from this medication.
Vonoprazan, a potassium-competitive acid blocker, was discussed as an alternative to proton pump inhibitors (PPIs). It has demonstrated rapid, strong, and sustained acid suppression, and unlike PPIs, it does not require acid for activation or specific meal timing to increase potency.
Clinical trials demonstrated additional benefits of vonoprazan. Compared to lansoprazole, vonoprazan for severe esophagitis showed an improvement of 70% versus 53% at two weeks and 92% versus 72% at eight weeks and was superior in maintaining healing.
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Emerging randomized evidence suggests lower clinically relevant bleeding with apixaban compared to rivaroxaban, supporting its use in patients with higher bleeding risk when clinically appropriate.
Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, was presented as a medication with proven cardiorenal benefit. The FIDELIO-DKD trial demonstrated reductions in kidney failure and improved cardiovascular outcomes in patients with type 2 diabetes and advanced chronic kidney disease (CKD) who are already optimized on renin-angiotensin system blockade.
Finerenone’s effects on blood pressure are minimal, and the main consideration for monitoring is potassium, as hyperkalemia can become a concern. Finerenone is currently FDA-approved for reducing the risk of kidney disease progression and cardiovascular events in patients with CKD associated with type 2 diabetes, and for reducing the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in patients with heart failure with left ventricular ejection fraction equal to or greater than 40%.
Intravenous fosfomycin is an emerging option for complicated urinary tract infections (cUTI), particularly those caused by multidrug-resistant organisms. The ZEUS trial demonstrated noninferiority of fosfomycin to piperacillin-tazobactam, with similar clinical cure rates.
However, its use is limited by its high sodium content and potential adverse reactions, including hypokalemia, hypophosphatemia, prolonged QT, and neutropenia. Current Infectious Diseases Society of America guidelines note that it is not first-line for empiric complicated urinary tract infection treatment due to lack of availability, difficulty with susceptibility testing, and concern for adverse events.
Several non-statin lipid-lowering agents can be used to achieve goals in patients at very high risk for atherosclerotic cardiovascular disease. For these patients, with a goal low-density lipoprotein (LDL) of 55 mg/dL, high-intensity statins remain first-line. If goals are not achieved despite optimizing statins, then ezetimibe or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (evolocumab, alirocumab) should be considered.
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GLP-1 receptor agonists were featured as part of the arsenal of expanding therapies with cardiovascular, metabolic, and renal benefits. More FDA-approved oral options are emerging in more convenient and accessible forms. Notably, the OASIS 1 and 4 trials saw significant weight reduction in both the 50-mg and 25-mg formulations of oral semaglutide, respectively.
Oral semaglutide has low bioavailability and requires strict administration conditions: it must be taken at least 30 minutes before food, drink, or other medications with water. Despite these dosing constraints, oral formulations are comparable to subcutaneous formulations in terms of weight loss, hemoglobin A1c reductions, and side effect profiles.
Hospitalists must consider GLP-1 receptor agonists in perioperative settings, similar to how advances in perioperative medicine have improved patient care.
Clear liquids for 24 hours prior to surgery are also recommended for patients at high risk for aspiration.
Hospitalists will need to stay up-to-date on the latest developments in pharmacotherapy.
