Long-Term Effects of Atorvastatin in Cardiovascular Disease
The Anglo-Scandinavian Cardiac Outcomes Trial investigated the long-term effects of atorvastatin, a cholesterol-lowering drug, on cardiovascular (CV) disease in hypertensive individuals with additional risk factors. The lipid-lowering arm of the trial randomized over 10,000 participants with total cholesterol <6.5 mmol/L to receive either atorvastatin 10 mg or a placebo for an average of 3.3 years. The initial results showed that atorvastatin significantly reduced the incidence of major CV events like myocardial infarction (MI) and stroke.
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A follow-up conducted approximately 20 years after the initial randomization and 17 years after the lipid-lowering arm's closure examined both nonfatal events and mortality data from the UK participants (n=4,605). This long-term analysis aimed to assess the enduring "legacy effects" of the initial atorvastatin treatment and the association between cholesterol levels achieved during the trial and subsequent CV outcomes.
The results of this extended follow-up revealed that participants initially assigned to atorvastatin still experienced a meaningful reduction in nonfatal MI and fatal coronary heart disease events (hazard ratio [HR] 0.81), total coronary events (HR 0.88), and CV mortality (HR 0.86) compared to those who received the placebo during the trial. This benefit persisted despite the fact that a majority of participants in both groups were taking statins in the years following the trial's conclusion, and their lipid profiles had become similar.
Further analysis showed a strong association between the mean LDL cholesterol levels achieved during the trial in the atorvastatin group and long-term CV outcomes. Each 1 mmol/L decrease in LDL was linked to lower risks of nonfatal MI and fatal coronary heart disease, total coronary events, heart failure, stroke, total CV events, CV mortality, and even all-cause mortality. This highlights the importance of early and effective cholesterol lowering.
Interestingly, although the original trial showed a reduction in stroke incidence with atorvastatin, the long-term follow-up didn't demonstrate a sizeable legacy benefit for stroke. The researchers propose this could be due to the complex and multifactorial nature of stroke. Despite some limitations in the long-term data collection, the findings strongly support the concept of a "legacy effect" of early statin intervention, suggesting that the initial period of treatment provides lasting CV protection. (Sever, P. S., et al. [2025]. Long-term benefits of atorvastatin on the incidence of cardiovascular events: The ASCOT-Legacy 20-year follow-up. Heart. Advance online publication. Retrieved April 2025 from https://heart.bmj.com/content/early/2025/03/25/heartjnl-2024-325104)
Released: May 2025
Nursing Drug Handbook
© 2025 Wolters Kluwer N.V., its subsidiaries and/or its licensors. All rights reserved.
Brexpiprazole for Adolescents with Schizophrenia
A randomized, double-blind, placebo-controlled phase 3 trial evaluated the efficacy and safety of brexpiprazole in adolescents (ages 13 to 17) with schizophrenia. Participants in the trial had a confirmed diagnosis of schizophrenia, a history of illness for at least 6 months, a need for antipsychotic medication, and a score of 80 or greater on the Positive and Negative Syndrome Scale (PANSS).
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The study enrolled 316 patients and randomized them to receive either brexpiprazole (2 to 4 mg/day), placebo, or aripiprazole (10 to 20 mg/day) for 6 weeks. The primary outcome was the change in PANSS total score from baseline to week 6. The analysis primarily focused on comparing brexpiprazole to placebo, with aripiprazole included as an active reference to validate the trial's sensitivity.
The study results showed that the brexpiprazole group had a greater improvement in PANSS total score compared to the placebo group at week 6 (least squares mean difference −5.33, p=0.014). The aripiprazole group also demonstrated a significant improvement compared to placebo, validating the study's design.
The brexpiprazole group also showed significant improvements in secondary outcomes, such as PANSS Positive subscale score, response rate, and Clinical Global Impression-Improvement score compared to placebo. In addition, post hoc analysis revealed a meaningful improvement in the PANSS General Psychopathology subscale score in the brexpiprazole group versus placebo.
The overall incidence of adverse events was similar between the brexpiprazole group and placebo. The most common adverse events reported with brexpiprazole were headache and nausea. Notably, no patients in the brexpiprazole group discontinued treatment because of adverse events.
This trial demonstrated that brexpiprazole is an effective treatment for reducing overall schizophrenia symptom severity in adolescents compared to placebo, with a generally favorable safety profile. These results, combined with prior data, support brexpiprazole as a potential treatment option for adolescents with schizophrenia. (Ward, C., et al. [2025]. Efficacy and safety of brexpiprazole in adolescents with schizophrenia: A multicountry, randomised, double-blind, placebo-controlled, phase 3 trial with an active reference. Lancet Psychiatry, 12[5], 345–354. Retrieved April 2025 from https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(25)00043-4/fulltext#tbl3)
Released: May 2025
Nursing Drug Handbook
© 2025 Wolters Kluwer N.V., its subsidiaries and/or its licensors. All rights reserved.
Cenobamate in Drug-Resistant Epilepsy
A retrospective, multicenter study analyzed the real-world effectiveness and tolerability of cenobamate as adjunctive therapy for adults with drug-resistant focal-onset seizures participating in Early Access Programs. The study included 298 patients with a long history of epilepsy (median 22 years) and a high number of previously failed antiseizure medications, with 41.9% having undergone epilepsy surgery. The primary efficacy endpoint was a 50% or greater reduction in seizure frequency after 3 months of maintenance therapy.
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The study found that cenobamate demonstrated significant effectiveness in this highly refractory patient population. At the 3-month maintenance mark, 49.3% of patients achieved at least a 50% reduction in seizures, and 13.6% became seizure-free. These response rates showed a trend of improvement over time, with the 12-month maintenance period showing 60% of patients achieving a 50% or greater seizure reduction and 45% achieving seizure freedom, although the number of patients in the later time points was smaller due to the Early Access Program duration.
Most adverse events were mild to moderate and consistent with the known safety profile of cenobamate, with fatigue, dizziness, and somnolence being the most frequent. Serious adverse drug reactions related to cenobamate were rare (1.0%) and occurred only during the titration phase. Cutaneous reactions, which were also mostly mild or moderate, occurred in 2.3% of patients during titration, leading to discontinuation or dosage reduction in most cases, but resolved over time.
The retention rate of cenobamate was notable, with approximately 70% of patients remaining on the treatment after 12 months. A trend toward the reduction of concomitant antiseizure medications was also observed during the cenobamate treatment period, suggesting a potential for simplifying medication regimens.
The study's findings suggest that cenobamate is a valuable adjunctive treatment option for patients with highly drug-resistant focal or combined generalized and focal epilepsy, offering sustained seizure reduction and improved quality of life for patients who have failed multiple prior therapies. (Rheims, S., et al. [2025]. Real-world effectiveness and tolerability of cenobamate in drug-resistant epilepsy: A retrospective analysis of the patients included into the Early Access Programs [EAP] in Germany, France, and United Kingdom. Epilepsia Open. Advance online publication. Retrieved April 2025 from https://onlinelibrary.wiley.com/doi/10.1002/epi4.70021)
Released: May 2025
Nursing Drug Handbook
© 2025 Wolters Kluwer N.V., its subsidiaries and/or its licensors. All rights reserved.
Inebilizumab in Generalized Myasthenia Gravis
Autoimmune myasthenia gravis is characterized by autoreactive B cells producing autoantibodies that disrupt neuromuscular transmission, leading to fluctuating muscle weakness. Current treatments include glucocorticoids, cholinesterase inhibitors, thymectomy, and immunosuppressants, which aim to reduce mortality and alleviate symptoms; however, limitations in efficacy, side effects, and poor response in some patients highlight the need for alternative therapies.
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Inebilizumab, a humanized monoclonal antibody targeting CD19 (expressed on a broad range of B cells), presents a promising treatment option. A phase 3, double-blind, placebo-controlled study, the Myasthenia Gravis Inebilizumab Trial (MINT), aimed to evaluate the efficacy and safety of inebilizumab in patients with generalized myasthenia gravis undergoing a protocol-specified glucocorticoid taper.
The MINT trial enrolled 238 participants with moderate to severe generalized myasthenia gravis who were positive for either acetylcholine receptor or muscle-specific kinase antibodies. Participants were randomized to receive either inebilizumab (300 mg on days 1, 15, and 183) or placebo intravenously. The primary endpoint was the difference from baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score at week 26. Secondary endpoints assessed changes in the Quantitative Myasthenia Gravis (QMG) score and MG-ADL score in each antibody-positive subgroup.
The results of the trial demonstrated significant clinical improvement in the inebilizumab group (−4.8 in MG-ADL score) compared to the placebo group (−2.3). This was evident in both the combined population and the acetylcholine receptor antibody-positive subgroup at week 26, with greater reductions in MG-ADL and QMG scores. Although the muscle-specific kinase antibody-positive subgroup also showed improvement in MG-ADL scores, the difference in QMG scores was not statistically significant.
As far as safety, the MINT trial showed that inebilizumab was generally comparable to placebo, with similar rates of adverse events. Common adverse events included headache and coronavirus disease-2019.
The MINT trial concluded that inebilizumab demonstrated efficacy and acceptable safety in adults with generalized myasthenia gravis, highlighting the therapeutic potential of CD19+ B-cell depletion for this condition. (Nowak, R. J., et al. [2025]. A phase 3 trial of inebilizumab in generalized myasthenia gravis. NEJM. Advance online publication. Retrieved April 2025 from https://www.nejm.org/doi/full/10.1056/NEJMoa2501561)
Released: May 2025
Nursing Drug Handbook
© 2025 Wolters Kluwer N.V., its subsidiaries and/or its licensors. All rights reserved.