Inpatient Insights
APhA Staff
SGLT-2 inhibitors could provide kidney and heart protection in patients with advanced CKD
The efficacy and safety of SGLT-2 inhibitors in patients with advanced CKD, defined as an eGFR <30 mL/min/1.73 m2, has not been adequately studied. Researchers from McGill University (Montreal) conducted a systematic review and meta-analysis of phase 3 randomized controlled trials of SGLT-2 inhibitors in adults with advanced CKD. The study was published in the June 2025 issue of Clinical Journal of the American Society of Nephrology. Ten randomized controlled trials from the Medline and Embase databases with a total of 4,800 patients with advanced CKD were included.
Patients were randomized to receive either placebo or an SGLT-2 inhibitor. A lower incidence of the primary composite kidney outcome (worsening kidney function, kidney failure, and kidney or cardiovascular death) was observed in the patients who received the SGLT-2 inhibitor treatment. The incidence of the primary cardiovascular outcome (cardiovascular death or hospitalization for heart failure) was lower in the SGLT-2 inhibitor arm. The use of SGLT-2 inhibitors did not increase the incidence of AKI, urine infections, fractures, or treatment discontinuation due to adverse events. The incidence of adverse events was similar in both groups.
The authors concluded that SGLT-2 inhibitors retain their kidney and cardiovascular protective effect in patients with advanced CKD, with no added safety concerns. ■
How common are major adverse cardiac events associated with haloperidol use?
Haloperidol is a dopamine antagonist commonly used to treat psychotic disorders such as schizophrenia, delirium, and dementia but is a frequent source of medication safety alerts because of its listing as a “known risk” QT interval–prolonging medication. Investigators at the Research Institute of St. Joe’s Hamilton and McMaster University (Canada) searched Medline, Embase, International Pharmaceutical Abstracts, and Cochrane Central for randomized controlled trials comparing haloperidol to placebo to determine the frequency and nature of proarrhythmic major adverse cardiac events, including death, nonfatal cardiac arrest, ventricular tachyarrhythmia including torsades de pointes, and seizure or syncope (MACE) associated with haloperidol.
The study, published in the June 2025 issue of PLOS One, included 84 trials and over 12,000 patients. Almost 25% of the trials reported mean or median ages older than 65 years with 44% involving participants with psychiatric diagnoses and 60% including electrocardiograms. There were 1,144 events, of which 97.8% were deaths, with 22 ventricular arrhythmias and three seizures or syncope. There was no difference in MACE with exposure to haloperidol compared to placebo, and I.V. haloperidol was not associated with increased risk of mortality.
The authors concluded that haloperidol was not arrhythmogenic or did not increase mortality in these largely short-duration trials. Further research to clarify actual clinical outcomes related to QT interval–prolonging medication is important to inform safe prescribing practices. ■
What is the neurotoxic concentration of cefepime in hematological patients treated with continuous infusion?
Cefepime-induced neurotoxicity (CIN) is a potential adverse effect of the antibiotic cefepime, particularly in individuals with impaired kidney function. It manifests as neurological symptoms such as encephalopathy, seizures, and myoclonus, often associated with reduced cefepime clearance and increased penetration into the central nervous system. While CIN is commonly described, neurotoxic concentration thresholds remain unclear. Researchers at Rennes University Hospital (France) conducted a single-center prospective study including patients with febrile neutropenia treated by continuous infusion of cefepime in the hematology department to assess the relationship between plasma cefepime exposure and the occurrence of neurotoxicity.
Both cefepime steady-state concentration measurement and neurological assessment were performed at defined time points during the first 10 days after the onset of cefepime, and attributability of cefepime was determined for each neurological event. Secondary objectives were to establish a cefepime steady-state concentration threshold discriminating the patients who experienced CIN and the control group and identify influencing covariates. A total of 134 patients were evaluated, and CIN occurred in 9.7% of the patients.
The study, published online in Clinical Infectious Diseases on June 24, 2025, showed that maximum steady-state cefepime concentrations were not significantly different between the two groups, and median neurotoxicity onset was 5 days. After multivariable analysis, both concomitant chimeric antigen receptor T-cell administration and each mg/mL increase in cefepime steady-state concentration were independently associated with CIN onset, and further analysis identified an adjusted threshold concentration of 36.7 mg/L to differentiate the two groups.
The authors concluded that their study shows that the cefepime neurotoxicity threshold of 36.7 mg/L confirms a lower toxicity threshold than for other b-lactams, offering an additional tool for the management of high-dose cefepime therapy. ■
Early tirofiban infusion after I.V. thrombolysis for stroke may prevent vascular reocclusion
I.V. thrombolysis within 4.5 hours after onset remains a standard treatment for acute ischemic stroke, but vascular reocclusion may occur after this treatment. The ASSET-IT investigators conducted a phase 3, multicenter, double-blind, randomized, placebo-controlled trial at 38 centers in China to investigate the use of tirofiban, a platelet glycoprotein IIb–IIIa receptor antagonist, to reduce macrovascular reocclusion.
They assigned patients with acute ischemic noncardioembolic stroke who presented within 4.5 hours after stroke onset and who were not eligible for thrombectomy to receive a 24-hour I.V. infusion of tirofiban or placebo within 60 minutes after thrombolysis with either alteplase or tenecteplase. The primary efficacy outcome was an excellent functional outcome, defined as a score of 0 to 1 on the modified Rankin scale, at 90 days. The safety outcomes were symptomatic intracranial hemorrhage within 36 hours and death at 90 days.
Over 800 patients were assigned to receive either tirofiban or placebo. At 90 days, a score of 0 to 1 on the modified Rankin scale was reported in a higher percentage of patients in the tirofiban group than in the placebo group (65.9% vs. 54.9%, respectively). Symptomatic intracranial hemorrhage occurred in 1.7% of the patients in the tirofiban group and none in the placebo group. Mortality at 90 days was 4.1% in the tirofiban group and 3.8% in the placebo group. The study was published online on July 4, 2025, in NEJM.
The authors noted that their study is limited in that it was conducted exclusively in China, which may constrain its generalizability to western populations. In addition, only patients with relatively mild stroke severity were enrolled, which could limit the generalizability of the results to more severe cases of ischemic stroke. Finally, the exclusion of patients with a history of AFib restricts the applicability of the results to populations in which cardioembolic stroke is the predominant cause. ■