Annals of Pharmacotherapy最新文献

Background: Dual antiplatelet therapy (DAPT) is essential after percutaneous coronary intervention (PCI) but increases gastrointestinal (GI) bleeding risk, necessitating acid suppressants. The cardiovascular safety of concomitant proton pump inhibitor (PPI) use with clopidogrel has been debated due to potential drug-drug interactions, although recent evidence suggests that these concerns may be less clinically significant.

Objective: This study aimed to compare the risk of cardiovascular events and the prevention of GI bleeding associated with the use of PPIs with histamine type 2 receptor antagonists (H2RAs) in patients receiving clopidogrel after PCI, and to investigate potential differences among PPIs.

Methods: In this retrospective cohort study conducted in Korea, 75 600 patients who had been discharged after PCI between September 2017 and August 2020 and maintaining DAPT of aspirin-clopidogrel for at least 90 days were divided into 2 groups: 20 843 patients received PPIs and 4239 patients received H2RAs. Propensity score matching resulted in 4238 patients in each group. The major outcome was a composite of acute myocardial infarction, acute ischemic stroke, revascularization, and in-hospital death up to 2 years of discharge. The secondary outcomes included major GI bleeding.

Results: For the composite outcome, the incidence was not significantly higher in the PPIs group than in the H2RAs group (PPIs vs H2RAs after matching: 260 [6.13%] vs 197 [4.65%]; hazard ratio = 1.13; 95% confidence interval = 0.94, 1.36). No significant differences were observed in each outcome comprising the composite and bleeding outcome. Subgroup analysis stratified by CYP2C19 inhibition potential also showed no significant differences.

Conclusion and relevance: Concomitant use of PPIs was not significantly associated with increased cardiovascular outcomes compared with concomitant use of H2RAs, and no significant differences in the potential interaction with CYP2C19 were observed in real-world data. These findings suggest that potential pharmacokinetic interactions may have limited clinical impact.

Background: To our knowledge, there are no data assessing sedation requirements in patients on buprenorphine/naloxone (Bup/Nx) prior to admission (PTA).

Objective: The purpose of this study was to determine the analgesia and sedation requirements in medical intensive care unit (MICU) patients who were on Bup/Nx PTA.

Methods: A retrospective, observational cohort, Institutional Review Board (IRB) approved trial of adult MICU patients on Bup/Nx PTA who were intubated on a fentanyl infusion vs those who were opioid naïve PTA. The primary outcome evaluated the total amount of fentanyl in morphine milligram equivalents (MME) in the first 72 hours after infusion initiation. Secondary outcomes included the total amount of additional opioids (in MME) and non-opioids in the first 72 hours, the time that Critical Care Pain Observation Tool (CPOT) score was >3 and the Richmond Agitation and Sedation Score (RASS) was >0 in the first 72 hours, the Bup/Nx dose at discharge, and intensive care unit (ICU) and hospital lengths of stay.

Results: Baseline characteristics were similar between the groups with the exception of the Bup/Nx group being younger. Seventy patients were included in the final analysis (35 in each group). Overall, the Bup/Nx group required more sedation than the control group over 72 hours, with a significantly higher amount of fentanyl used in the first 24 hours (191.2 MME vs 119.0 MME, P = 0.033). Although not significant, there was also increased propofol, dexmedetomidine, midazolam, and ketamine use in the Bup/Nx group. The CPOT and RASS were higher for the Bup/Nx group compared to the control group in the first 72 hours (percentage of time CPOT score >3 in 33.3% vs 28.6% [P = 0.245] and percentage of time RASS >0 in 22.2% vs 12.5% [P = 0.183]).

Conclusion and relevance: This study demonstrated an increased opioid and non-opioid sedation requirement in patients taking Bup/Nx PTA as compared to the opioid-naïve control group. These data suggest a multimodal sedation and analgesic approach may be appropriate for this patient population.

Objective: The objective of the study is to analyze the pharmacology, efficacy, and safety of ustekinumab-ttwe in the treatment of moderate-to-severe plaque psoriasis.

Data sources: PubMed, Embase, and ClinicalTrials.gov were searched using the following search terms: ustekinumab, biosimilar, ustekinumab-ttwe, Pyzchiva, SB17, and psoriasis.

Study selection and data extraction: Articles published in English between January 9, 2015, and June 21, 2025, related to the pharmacology, pharmacokinetics, efficacy, safety, immunogenicity, and clinical trials were reviewed.

Data synthesis: Search results from PubMed and EMBASE yielded 259 articles, and 12 studies from Clinicaltrials.gov. Only 2 clinical trials of ustekinumb-ttwe's use in psoriasis were identified and were included in analysis. The pharmacokinetic parameters of ustekinumab-ttwe (SB17), European Union-sourced ustekinumab (EU-UST) and United States-sourced ustekinumab (US-UST) were similar in its phase I trial. In addition, a phase III trial comparing the efficacy of ustekinumab-ttwe to ustekinumab showed that the difference of percent change from baseline of the Psoriasis Area and Severity Index (PASI) score between the 2 groups was comparable with a change of 85.7% for ustekinumab-ttwe (95% confidence interval [CI] = [-3.78, 2,58]) and 86.4% for ustekinumab (90% CI = [-3.34, 1.93]).Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:The pharmacology, pharmacokinetics, efficacy, safety, and immunogenicity of ustekinumab-ttwe and reference ustekinumab were equivalent, demonstrating its role as a biosimilar. There are no current clinical trials directly comparing ustekinumab-ttwe with ustekinumab's other biosimilars.

Conclusion: Ustekinumab-ttwe's equivalence to its reference biologic ustekinumab creates another treatment option for patients with moderate- to- severe plaque psoriasis.

Background: The guidelines recommend intravenous (IV) iron for patients with heart failure (HF) with a reduced or mildly reduced ejection fraction. IV iron is often administered during hospitalization. However, care transitions from inpatient to outpatient settings for IV iron are suboptimal, and only about one-third of patients receive follow-up iron study measurements to assess the need for IV iron at outpatient settings after inpatient IV iron. Limited data is available to improve the current practice of IV iron during care transitions.

Objective: To evaluate the post-discharge performance of the pharmacist-led iron deficiency transitions of care initiative for patients with HF who received IV iron during hospitalization.

Methods: This retrospective cohort study included patients with HF who received ferric gluconate during hospitalization and was managed by the pharmacist-led iron deficiency transitions of care service (post-implementation group), compared to patients managed under the usual care during hospitalization (pre-implementation group). The primary outcome was the attainment of follow-up iron study and hemoglobin measurements within 6 months after the ferric gluconate induction course. The secondary outcomes included the provision of IV iron maintenance doses at outpatient settings for patients who had iron deficiency after the induction course.

Results: A total of 43 patients in the post-implementation group and 92 patients in the pre-implementation group were included in the analysis. The primary outcome was significantly higher in the post-implementation group (83.7 vs. 28.3%, p<0.001). For patients who had follow-up labs and were indicated for IV iron maintenance doses, a significantly higher number of patients in the post-implementation group received IV iron maintenance doses compared to the pre-implementation group (80 vs. 14.3%, p<0.001).

Conclusion and relevance: The pharmacists-led iron deficiency transitions of care service can improve attainment of follow-up labs and provision of IV iron maintenance doses during care transitions from inpatient to outpatient settings.

Background: Previous retrospective studies involving mixed intensive care unit (ICU) populations found antipsychotic continuation rates ranging from 21% to 61% at hospital discharge. Surgical ICU admission was cited as a risk factor for antipsychotic continuation, although data in the trauma population are limited.

Objective: The purpose of this study was to evaluate the number of critically ill trauma patients with escalated psychotropic medications in the surgical ICU and the rate of continuation at ICU transfer and hospital discharge.

Methods: This single-center, retrospective, Institutional Review Board (IRB)-approved study examined adult trauma patients admitted to the surgical ICU at an urban Level 1 Trauma and Academic Medical Center from December 1, 2021, to May 31, 2023. Patients were excluded if they had a history of select psychiatric disorders or were in the ICU for less than 48 hours. Prior psychotropic medication use was noted, and escalation was defined as a new or increased dose of psychotropic medication. The incidence of delirium and agitation was recorded to assess the indication for psychotropic medication escalation. The primary and secondary outcomes were the percentage of patients with escalated psychotropic medications in the ICU who were continued on therapy at the time of ICU transfer and hospital discharge, respectively.

Results: Four hundred and twenty-four patients admitted to the surgical ICU were included; 51.4% were escalated on a psychotropic medication while in the ICU. Nearly 35% and 31.8% of the overall population were continued on psychotropic medication at ICU and hospital discharge, respectively. Of patients on psychotropic medication at hospital discharge, 55.6% were discharged to acute rehabilitation, 28.9% to home, and 13.3% to long-term care.

Conclusion and relevance: Escalation of psychotropic medications was common in trauma patients admitted to the surgical ICU. Further investigation into the appropriateness of psychotropic medication prescription during care transitions is needed.

Background: Diabetic ketoacidosis (DKA) is a severe complication of diabetes mellitus requiring insulin. However, there is no consensus on insulin infusion titration strategies, resulting in varied nomograms and potentially suboptimal management. Limited comparative data on insulin nomograms underscore the need for a standardized, evidence-based approach.

Objective: The purpose of this study is to evaluate the safety and effectiveness of 3 DKA nomograms.

Methods: This multicenter, retrospective observational study included adult patients with confirmed DKA treated with IV insulin for ≥3 hours. Each site used a different variable-rate nomogram: variable rate weight-adjusted IV insulin infusion with no bolus (VR-W-NB), variable-rate IV insulin infusion with bolus (VR-B) or variable-rate IV insulin infusion with no bolus (VR-NB). The primary endpoint was the incidence of hypoglycemia (<70 mg/dL). Secondary outcomes included time to DKA resolution and recurrence.

Results: A total of 350 patients were included. Hypoglycemia occurred in 36.2% of patients in the VR-W-NB cohort, 23.9% of patients in the VR-B cohort and 6.8% of patients in the VR-NB cohort (P < 0.01). After controlling for confounding factors, hypoglycemia remained the highest in the VR-W-NB (odds ratio [OR] = 6.2, 95% confidence interval [CI] = 2.5-15.3, P < 0.01) and VR-B (OR = 5, 95% CI = 2.1-12.1, P < 0.01) cohorts compared with the VR-NB cohort. Diabetic ketoacidosis resolution was significantly shorter in patients receiving VR-W-NB (median of 9.7 hours, interquartile range [IQR] = 5.6-16.9) compared with those receiving VR-B (12.7 hours, IQR = 9.2-25) and VR-NB (16.1 hours, IQR = 10-24.5). DKA recurrence was higher in those treated with VR-B (19.7%) compared with those treated with VR-W-NB (7%) and VR-NB (15.5%) (P = 0.02).

Conclusion and relevance: The VR-W-NB was associated with a higher incidence of hypoglycemia and faster DKA resolution compared with VR-B and VR-NB. These findings support the need for prospective studies to define optimal insulin strategies that improve safety, effectiveness, and resource utilization.

Background: Heart failure with reduced ejection fraction carries high morbidity and mortality. Guideline-directed medical therapy (GDMT) improves outcomes, yet real-world use is often suboptimal. Multiple scoring tools quantifying GDMT optimization have been developed to identify areas of improvement, including GDMT count, Optimal Medical Therapy (OMT), modified OMT (mOMT), and Kansas City Medical Optimization (KCMO) scores. Their clinical utility in predicting readmissions is uncertain.

Objective: To evaluate the association between four GDMT scoring systems and 30- and 90-day heart failure (HF) readmissions.

Methods: This multi-center, retrospective cohort study included adults with a left-ventricular ejection fraction ≤40% hospitalized for HF across five academic medical centers between February 2021 and July 2023. Patients discharged on ≥1 GDMT class with ≥1 healthcare encounter within 90 days were included. GDMT scores were calculated at discharge, and their associations with 30- and 90-day HF readmissions were analyzed using mixed-effects Cox proportional hazards models adjusted for clinical covariates.

Results: Among 544 patients, 13.1% experienced 30-day and 26.8% experienced 90-day HF readmissions. At 30 days, no GDMT score was significantly associated with readmission. At 90 days, higher OMT (hazard ratios [HR]: 0.93, 95% CI: 0.86-0.99) and mOMT (HR: 0.94, 95% CI: 0.88-0.99) scores were associated with lower readmission risk, whereas GDMT count and KCMO scores were not. Patients on minimal GDMT regimens contributed disproportionately to 90-day readmissions.

Conclusion and relevance: In this multi-center cohort, OMT and mOMT scores, but not GDMT count or KCMO, were associated with 90-day HF readmissions. Findings highlight the potential utility of simpler GDMT scoring systems while underscoring the need for refined tools incorporating dose intensity, class-specific weighting, and longitudinal therapy to better guide optimization efforts.