Annals of Pharmacotherapy最新文献

Background: Heart failure (HF) places a significant burden on the health care system, driven primarily by HF hospitalizations. While HF guidelines recommend initiation of quadruple guideline-directed medical therapy (GDMT) in patients with HF with reduced ejection fraction (HFrEF), in-hospital initiation of quadruple therapy remains a clinical challenge, particularly in patients with additional high-risk comorbidities.

Objective: The purpose of this study was to compare the efficacy and safety of triple GDMT with a sodium-glucose cotransporter inhibitor (SGLTi) vs mineralocorticoid receptor antagonist (MRA) added to beta blocker and angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB)/angiotensin receptor-neprilysin inhibitor (ARNi).

Methods: This retrospective cohort study was conducted in hospitalized patients with acute HFrEF. Patients who received triple GDMT therapy with a SGLTi or MRA added to beta blocker and ACEi/ARB/ARNi therapy at discharge were compared. The primary outcome was 90-day readmission for HF with secondary outcomes of 30-day readmission for HF and 90-day readmission for GDMT-associated adverse events.

Results: A total of 210 patients were included (SGLTi group, n = 105; MRA group, n = 105). Rates of 90-day readmission for HF between SGLTi and MRA groups were 23 (21.90%) vs 15 (14.29%); P = 0.1516. After adjusting for co-variables associated with 90-day readmission, 90-day readmission for HF was not significantly different in patients in the SGLTi vs MRA group (adjusted hazard ratio = 1.742, 95% confidence interval [CI] = 0.833 to 3.434; P = 0.1092). Rates of 90-day readmission for GDMT-associated adverse events were similar between groups.

Conclusion and relevance: In this cohort of patients receiving triple GDMT at discharge after hospitalization for acute HFrEF, triple therapy with an SGLTi vs MRA resulted in similar rates of 90-day HF hospitalization.

Objective: Pharmacists care for patients with intracranial bleeding such as those with subarachnoid hemorrhage (SAH) or subdural hematoma (SDH), although these bleeding events are often generically termed "head bleed." This over-simplified term refers to a heterogeneous group of life-threatening intracranial hemorrhages, each with a distinctive etiology and treatment paradigm.

Data sources: Common intracranial hemorrhage types were reviewed to identify the scope of this narrative review.

Study selection and data abstraction: Relevant studies and guidelines pertinent to the selected topic were considered.

Data synthesis: Various hemorrhage types such as intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and SDH fall into the colloquialism of "head bleed." However, these and other hemorrhage types are radiographically distinct and often require different management strategies. Surgical management is helpful in some of these situations (SDH, SAH) and limited in scope for others (ICH). Pharmacotherapy for reversal of coagulopathy and treatment of elevated intracranial pressure may be considered similar across the spectrum of intracranial bleeding pathologies, while other factors such as seizure prophylaxis and blood pressure control depend on the bleeding type.

Relevance to patient care and clinical practice: Differences in the need for surgical intervention, neurologic monitoring, cerebral perfusion changes, risk of seizure, optimal blood pressure, and other clinical characteristics make each type of intracranial bleeding unique.

Conclusions: Pharmacists should be aware of the differences in surgical and pharmacotherapy strategies among these intracranial hemorrhages to optimize care for this neurocritical care population.

Objective: To review the pharmacology, pharmacokinetics, safety, and efficacy of sotatercept for the management of pulmonary arterial hypertension (PAH).

Data sources: A literature search in PubMed, EMBASE, and the National Institutes of Health Clinical Trials Registry (http://www.

Clinicaltrials: gov) was conducted from January 2009 to June 2025 using the keyword "sotatercept."

Study selection and data extraction: Phase II and III trials assessing sotatercept's safety and efficacy were included. Initially, 796 trials were yielded, and 4 trials were included after application of inclusion criteria.

Data synthesis: The findings from this review indicate that sotatercept is an overall safe and effective option for improving PAH outcomes when added to established PAH pharmacotherapy. Trials found improvement in outcomes such as pulmonary vascular resistance, 6-minute walk distance, and a reduction in a composite outcome of all-cause death, lung transplantation, and hospitalization for worsening PAH.Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:Sotatercept targets a new pathway in PAH that directly addresses inappropriate cellular proliferation and the underlying pathophysiology in PAH. The benefit with sotatercept was found when added to background PAH therapy, but limitations for use include cost and need for reconstitution by the patient or caregiver.

Conclusion and relevance: Sotatercept offers a novel and effective approach to management of patients with PAH on background therapy. Additional data regarding long-term outcomes is needed-studies evaluating this are in progress.

Background: Definitive management of acute immune thrombocytopenia (ITP) in hospitalized patients remains variable. A lack of standardized treatment protocols has led to varying treatment sequences and inconsistent utilization of resources. A viable remedy exists in developing a standardized sequential treatment protocol balancing therapeutic efficacy with financial responsibility.

Objective: The purpose of this study was to evaluate the pharmacoeconomic impact and clinical efficacy of an inpatient pharmacist-developed sequential ITP treatment protocol. The primary objective was to evaluate drug cost of ITP treatment per patient pre- versus post-protocol implementation. Secondary objectives included hospital length of stay and platelet count at discharge.

Methods: This multicenter, retrospective, quasi-experimental, institutional review board-approved study assessed hospitalized patients treated for acute ITP between October 2018 and June 2023 at Sarasota Memorial Health Care System. The ITP protocol was implemented on June 1, 2022. Retrospective chart review was performed on adult patients diagnosed with ITP who received one or more medications to treat ITP. Patients less than 18 years old, pregnant, or with sustained platelet counts greater than 100 x 10³/µL throughout admission were excluded. Propensity score matching was used to estimate the protocol effect on primary and secondary outcomes.

Results: Of the 450 patients screened, 168 met inclusion criteria, with 115 patients assigned to the pre-protocol arm and 53 patients assigned post-protocol. In the pre-protocol cohort, 53 propensity-matched pairs were evaluated. The median drug cost of treatment was significantly higher in the pre- protocol arm compared with post-protocol ($24 899 vs $13 833; P < 0.001). There was no difference in either secondary outcome of median length of hospital stay (5.5 vs 5.2 days; P = 0.987) or median platelet count at discharge (82 vs 72; P = 0.477).

Conclusion and relevance: Implementation of a standardized sequential ITP treatment protocol at a community hospital resulted in substantial cost savings while maintaining positive clinical outcomes.

Objective: This article reviews clinical trial data that assess the safety, efficacy, and clinical application of roflumilast, a phosphodiesterase-4 inhibitor, for the treatment of seborrheic dermatitis.

Data sources: A review of the literature was conducted in MEDLINE (Pubmed) and Clinicaltrials.gov from January 1, 1950 to April 13, 2025 using the search terms: "Roflumilast" and "seborrheic dermatitis."

Study selection and data extraction: Relevant articles in English relating to the safety, efficacy, pharmacodynamics, and pharmacokinetics were included.

Data synthesis: In one phase IIa clinical trial, 73.8% of patients treated with roflumilast achieved Investigator Global Assessment (IGA) success, compared with 40.9% in the vehicle group at 8 weeks (P < 0.001). A phase III trial found 79.5% of patients in the roflumilast group achieved IGA success at week 8, compared with 58.0% in the vehicle group (P < 0.001). Furthermore, there were statistically significant reductions in erythema, scaling, and itch severity in the roflumilast group. Roflumilast was well tolerated, with adverse events comparable with vehicle foam.Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:Roflumilast is the first phosphodiesterase-4 inhibitor approved by the Food and Drug Administration for the treatment of seborrheic dermatitis. Based on 2 clinical trials, roflumilast has a positive safety profile, is efficacious, and is easy to apply, highlighting its utility in treating seborrheic dermatitis.

Conclusion: Roflumilast is effective in treating seborrheic dermatitis. Future trials should compare its safety and efficacy with other drugs.

Background: Direct-acting oral anticoagulants (DOACs) are first-line therapy for atrial fibrillation and for venous thromboembolism prevention and treatment. In addition, proton pump inhibitors (PPIs) are recommended by the ACC Expert Consensus for patients receiving DOAC.

Objective: To determine the risk of clinically important thromboembolic and bleeding events and death in patients concomitantly prescribed DOACs and PPIs compared with DOAC alone.

Methods: We undertook a population-based cohort study of Ontario residents aged 66 years or older who were newly dispensed a DOAC from 2009 to 2020. The primary outcome was a composite of clinically relevant bleeding, thrombotic events, and all-cause death. We then used a time-dependent Cox regression model to estimate the adjusted hazard of outcomes during time periods where patients were exposed vs not exposed to PPI.

Results: We included 283 771 new DOAC users (mean age 78.3 years, 49.4% female). The age/sex-standardized outcome event rate of the composite outcome was higher in the DOAC-PPI cohort [20.2 (95% CI 20.0-20.5) per 100 person-years] than in the DOAC-alone cohort [15.2 (95% CI 15.1-15.4) per 100 person-years]. In time-dependent Cox regression analyses examining time periods during DOAC-PPI co-therapy vs DOAC alone, risks were elevated for all outcomes during periods of PPI co-therapy, suggesting residual confounding. In a secondary analysis of patients receiving DOAC-PPI co-therapy (n = 115 493), periods of DOAC-PPI co-therapy were associated with a greater hazard for death (HR 2.24, 95% CI 2.14-2.35), but a lower risk for both thrombosis (HR 0.93, 95% CI 0.89-0.96) and clinically relevant bleeding (HR 0.79, 95% CI 0.76-0.81).

Conclusion and relevance: Our cohort study of older adults suggests that DOAC-PPI co-therapy is associated with decreased upper GI bleeding but increased mortality. Since the implications are major and may be due to residual confounding, we recommend that the findings be verified in randomized trials before clinical application.

Background: Intravenous fluids are commonly used in postcardiac surgery to maintain or increase intravascular volume. While volume expansion after cardiac surgery is often necessary, the optimal fluid type to use is not established.

Objective: The objective of the study is to evaluate cost-savings and clinical outcomes of an albumin minimization protocol for postcardiac surgery fluid resuscitation at a surgical intensive care unit in a community teaching hospital.

Methods: This was a single-center retrospective cohort study of patients who received fluid resuscitation after open heart coronary artery bypass surgery or valvular surgery while on cardiopulmonary bypass at a community teaching hospital between February 2021 and May 2022. Cohorts were split up prior to the implementation of an albumin minimization protocol that was implemented in September 2021. The primary outcome was the amount of albumin or crystalloid fluids received after surgery, and the overall cost of intravenous fluids after surgery. Secondary outcomes included 30-day mortality, acute kidney injury, hours on oxygen support, hours on vasopressors, multiple vasopressors used, perioperative blood product transfusions, and 72-hour surgery take back.

Results: Of 434 total patients evaluated, 400 patients met criteria for inclusion. Baseline characteristics were balanced between the 2 groups. Average surgical time was shorter in the postprotocol arm. Per patient use of albumin decreased by 27.1 g (22.8-31.4) while crystalloid fluid use increased by 1 L (0.9-1.2) after implementation of the albumin minimization protocol. Average cost savings were approximately $178 per surgery. No statistically significant difference was seen in any of the secondary safety and efficacy outcomes.

Conclusion and relevance: This study adds to the body of literature suggesting that the use of an albumin minimization protocol after open heart cardiac surgery was safe and effective. A significant reduction in cost and utilization of albumin was seen in the study without affecting patient outcomes.

Nontraditional models of care, including pharmacist-led management, have emerged to improve access to evidence-based cystitis treatment. Drawing from studies in Canada, New Zealand, the United Kingdom, and the United States, evidence demonstrates that pharmacists can safely and effectively manage cystitis using established protocols without compromising antimicrobial stewardship. These models expedite patient access to care while maintaining quality and safety. With more than 15 years of international experience supporting pharmacist-led cystitis management, policymakers and professional organizations have robust data to guide implementation and inform ongoing debates on optimizing care delivery.

Background: Pharmacotherapy with stimulant or nonstimulant medications is recommended as first-line treatment for attention-deficit/hyperactivity disorder (ADHD). Among patients prescribed stimulants, concomitant opioid use may increase the risk of drug dependence, exacerbate comorbid conditions, and compromise treatment adherence. However, limited evidence exists on the risk factors for initial opioid prescription in this population.

Objective: To identify factors associated with incident opioid prescriptions among patients with ADHD prescribed stimulant therapy.

Methods: We conducted a retrospective cohort study using the Merative® MarketScan® Commercial Claims and Encounters Database (2010-2020). We identified patients with ADHD who initiated stimulant therapy and followed them for 1 year to assess incident opioid prescription. Cox proportional hazards models were used to evaluate factors associated with opioid initiation.

Results: Among 380 494 patients with ADHD initiating stimulants (mean age: 21.2 years; 56.5% male), 14.2% received an opioid prescription within 1 year. Factors significantly associated with incident opioid prescription included age ≥35 years (adjusted hazard ratio [aHR]: 10.84; 95% CI: 10.43-11.26), gender(aHR [female]:1.29; 95% CI: 1.27-1.31), geographic region (aHR [West]: 1.58; 95% CI: 1.52-1.64), multiple chronic conditions (aHR: 1.61; 95% CI: 1.54-1.67), anxiety (aHR: 1.19; 95% CI: 1.17-1.22), depression (aHR: 1.16; 95% CI: 1.14-1.19), severe mental illnesses (aHR: 1.18; 95% CI: 1.13-1.23), substance use disorders (SUDs) (aHR: 1.69; 95% CI: 1.63-1.75). Receipt of behavioral therapy before ADHD pharmacotherapy (aHR: 0.89; 95% CI: 0.87-0.92) was associated with a lower risk of receiving incident opioid prescriptions.

Conclusions and relevance: Several demographic factors (e.g., age, gender, geographic region) and clinical factors (e.g., history of mental health conditions and SUDs) are associated with opioid initiation among stimulant-treated patients with ADHD. These findings may inform clinical strategies to mitigate unnecessary opioid exposure and associated harms.