European Journal Of Clinical Pharmacology[JOURNAL]
Sun
200 papers
Trough concentration of voriconazole and its association with central nervous system toxicity in patients with hematologic malignancies: a retrospective cohort study.
Zhang Q, Chen J, Tan W … +3 more , Li W, Tan L, Wen X
Eur J Clin Pharmacol · 2026 Mar · PMID 41805996 · Publisher ↗
PURPOSE: Voriconazole (VRC), a broad-spectrum antifungal agent, is commonly used for the treatment and prophylaxis of invasive fungal disease (IFD) in patients with hematologic malignancies following chemotherapy. Howeve...
PURPOSE: Voriconazole (VRC), a broad-spectrum antifungal agent, is commonly used for the treatment and prophylaxis of invasive fungal disease (IFD) in patients with hematologic malignancies following chemotherapy. However, its clinical application is often limited by central nervous system (CNS) toxicity. CNS toxicity was defined using the National Cancer Institute criteria, such as hallucinations and anxiety. The aim of this study was to identify risk factors associated with VRC-induced CNS toxicity and to determine the plasma trough concentration (Cmin) threshold. METHODS: This retrospective cohort study analyzed clinical data from 126 patients with hematologic malignancies who received VRC after chemotherapy and underwent therapeutic drug monitoring (TDM). RESULTS: The 126 patients, 30 (23.8%) developed CNS toxicity related to VRC. The median time to onset of CNS toxicity was 6 days following VRC initiation. VRC Cmin levels were significantly associated with an increased risk of CNS toxicity (odds ratio: 2.08; 95% confidence interval [CI]: 1.56–2.78, p < 0.001 per 1 mg/L increment on multivariate analysis). Receiver operating characteristic curve analysis identified a Cmin threshold of 4.79 mg/L for predicting CNS toxicity, with an area under the curve of 0.89 (95% CI: 0.82–0.97; P < 0.001) and sensitivities and specificities of 0.87 and 0.85, respectively. CONCLUSION: Therefore, routine TDM is recommended for patients with hematologic malignancies receiving VRC to minimize the risk of CNS toxicity.
Risk drugs and comorbidities in patients with torsade de pointes.
Andersson ML, Fastbom J, Danielsson B … +3 more , Wikström E, Dahl ML, Nowinski K
Eur J Clin Pharmacol · 2026 Mar · PMID 41792521 · Publisher ↗
Abstract loading — click title to view on PubMed.
The association between proton pump inhibitor use and the risk of mortality in patients with kidney disease: a systematic review and meta-analysis.
Park I, Song HJ, Seo HJ
Eur J Clin Pharmacol · 2026 Mar · PMID 41792514 · Publisher ↗
BACKGROUND: Use of proton pump inhibitor (PPI) has been associated with adverse health outcomes, including increased risk of all-cause mortality. Evidence suggests that individuals with kidney disease who use PPIs may ex...
BACKGROUND: Use of proton pump inhibitor (PPI) has been associated with adverse health outcomes, including increased risk of all-cause mortality. Evidence suggests that individuals with kidney disease who use PPIs may experience higher mortality, though the nature of this association is not well established. OBJECTIVE: To assess the relationship between PPI use and mortality among individuals with kidney disease through a systematic review and meta-analysis. METHODS: A comprehensive search of Ovid-MEDLINE, Ovid-EMBASE, and Cochrane CENTRAL was conducted through April 2025 to identify randomized controlled trials and observational studies examining mortality among PPI users versus non-users with kidney disease. Both unadjusted mortality rates and adjusted hazard ratios (aHRs) were extracted. A random-effects meta-analysis was performed using the Hartung-Knapp-Sidik-Jonkman method, with the Sidik-Jonkman estimator used for between-study variance (τ). Study heterogeneity was evaluated using the I statistic and Cochran's Q test. Subgroup analyses were carried out based on follow-up length, population characteristics, geographic region, and risk of bias level. RESULTS: The review included 24 observational studies encompassing 216,032 individuals with kidney disease. Across 20 cohorts from 17 observational studies, mortality was 23.2% among PPI users and 22.1% among non-users. Pooled adjusted estimates from 18 studies (20 cohorts) indicated a significantly increased risk of death in PPI users (aHR 1.26; 95% CI, 1.11-1.42). Considerable heterogeneity was observed, but subgroup analyses revealed consistent trends. CONCLUSIONS: Our meta-analysis showed that PPI use was linked to elevated mortality risk in kidney disease populations. Careful consideration is advised when prescribing PPIs, and further research is needed.
Colistin-induced acute kidney injury in neonates with sepsis and its association with plasma colistin concentration: a prospective cohort study.
Kagnur R, Mukhopadhyay K, Shafiq N … +3 more , Bhandari RK, Kumar J, Pandey AK
Eur J Clin Pharmacol · 2026 Mar · PMID 41792462 · Publisher ↗
BACKGROUND: Colistin is increasingly used as a reserve antibiotic for multidrug-resistant (MDR) Gram-negative infections. However, colistin-induced acute kidney injury (AKI) is under-reported in neonates with sepsis. OBJ...
BACKGROUND: Colistin is increasingly used as a reserve antibiotic for multidrug-resistant (MDR) Gram-negative infections. However, colistin-induced acute kidney injury (AKI) is under-reported in neonates with sepsis. OBJECTIVES: To evaluate the association and causality between colistin use and AKI in neonatal sepsis, and to explore the correlation between steady-state plasma colistin concentration and AKI development. METHODS: In this prospective cohort study, neonates receiving colistin for proven or probable sepsis were enrolled. Exclusion criteria included major congenital anomalies and death within 72 h of life. Causality of colistin-induced AKI was assessed using the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) criteria. Steady-state colistin levels were measured after the sixth dose. AKI was defined and staged according to KDIGO guidelines. RESULTS: A total of 40 neonates were enrolled (mean gestational age: 29.3 ± 3.1 weeks). The mean duration of colistin therapy was 10.1 ± 0.8 days. AKI occurred in 28/40 (70%), of whom 13 had moderate-to-severe AKI. According to WHO-UMC criteria, 10/28 (35%) AKI cases were classified as “possible” colistin-induced nephrotoxicity. The median (IQR) steady-state colistin concentration was 1.08 (0.53,2.53) mg/L overall. Plasma colistin levels were higher in neonates with “possible” nephrotoxicity (median: 2.09 mg/L) compared with those classified as “unlikely/unclassifiable” (0.95 mg/L) and the non-AKI group (1.04 mg/L) (p = 0.3). Thirteen neonates (33%) died during hospitalization. CONCLUSION: Possible colistin induced AKI was seen in nearly one third cases. Higher steady-state plasma colistin levels was seen in the possible colistin-induced AKI group, highlighting the need for therapeutic drug monitoring and cautious use in this vulnerable population.
Effect of transporter gene polymorphisms and valproate co-medication on the steady-state disposition of lamotrigine and their effect on efficacy in adults with epilepsy.
Wu C, He R, Zheng J … +5 more , Yang J, Pan Y, Tao R, Lan X, Wang J
Eur J Clin Pharmacol · 2026 Mar · PMID 41786984 · Publisher ↗
Background and Objectives The steady-state disposition lamotrigine (LTG) varies widely among patients with epilepsy, especially in the presence of concomitant antiseizure drugs. In this study, we investigate the potentia...
Background and Objectives The steady-state disposition lamotrigine (LTG) varies widely among patients with epilepsy, especially in the presence of concomitant antiseizure drugs. In this study, we investigate the potential role of transporter gene polymorphisms in ABCC1, ABCC2, ABCG2, SLCO1A2 and SLCO1B1 on the steady-state disposition of LTG and on the lamotrigine-valproate (LTG-VPA) interaction, and their effect on the therapeutic efficacy in adults with epilepsy.Methods Adults with epilepsy on LTG monotherapy or LTG-VPA treatment were genotyped and steady-state LTG and VPA morning troughs were determined. The number of seizures within a one-year follow-up period was used to evaluate the antiepileptic efficacy.Results A total of 331 patients with epilepsy were enrolled, including 267 receiving LTG monotherapy and 64 receiving LTG combined with VPA. Steady-state LTG plasma troughs and normalized troughs were significantly higher in the LTG-VPA group than in the LTG monotherapy group (8.82 vs. 4.43 µg/mL, p < 0.001; 4.12 vs. 1.51 µg/mL, p < 0.001). Among the investigated transporter gene polymorphisms, only SLCO1B1 rs4149032 showed a significant association with LTG concentrations in monotherapy. Overall, 77.8% (242/331) of patients achieved a therapeutic response, with a markedly higher response rate in the LTG-VPA group compared with LTG alone (92.1% vs. 76.5%, p = 0.0009). Multivariate logistic regression identified LTG plasma concentration and sex as independent predictors of favorable seizure control.Conclusions The polymorphisms of SLCO1B1 rs4149032 may affect LTG plasma troughs in patients with LTG monotherapy. LTG plasma concentrations are a major determinant of antiepileptic therapeutic efficacy with or without VPA co-therapy, with higher exposure associated with improved seizure control.
Cost-effectiveness analysis of anti-VEGF drugs in the treatment of visual impairment due to diabetic macular edema: A systematic review.
Hasoumi M, Alipour V, Ahmadieh H … +2 more , Arabloo J, Jahangiri R
Eur J Clin Pharmacol · 2026 Feb · PMID 41739212 · Publisher ↗
PURPOSE: This systematic review aims to evaluate the cost-effectiveness of anti–vascular endothelial growth factor (anti-VEGF) drugs in the treatment of diabetic macular edema (DME), providing a comprehensive synthesis o...
PURPOSE: This systematic review aims to evaluate the cost-effectiveness of anti–vascular endothelial growth factor (anti-VEGF) drugs in the treatment of diabetic macular edema (DME), providing a comprehensive synthesis of economic and quality of life outcomes. METHODS: A systematic review was conducted following PRISMA guidelines. Scopus, PubMed, Embase, and Web of Science core collection, DARE, NHSEED, HTA, and Google scholar were searched to September 7, 2025, without language or publication type restrictions. Eligible studies compared the cost-effectiveness of anti-VEGF drugs for DME. We extracted economic outcomes from each study, including incremental cost-effectiveness ratios (ICERs), quality-adjusted life years (QALYs) and costs, and evaluated methodological quality using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. All costs were adjusted to 2024 US dollars. RESULTS: Of 2,136 studies identified, 12 met the inclusion criteria. Findings were heterogeneous across settings and perspectives. Bevacizumab showed the greatest economic value, achieving comparable gains in visual acuity to aflibercept and ranibizumab at a substantially lower cost, while differences between ranibizumab and aflibercept were less consistent and varied across studies. Conbercept, assessed in one Chinese study, dominated ranibizumab in real-world conditions. Faricimab, analyzed in the UK, Colombia, and Japan, was consistently cost-effective or dominant relative to ranibizumab, aflibercept, bevacizumab, and brolucizumab, primarily due to fewer injections and lower monitoring costs. Cost-effectiveness varied with assumptions about time horizon, pricing, treatment frequency, perspective, and willingness-to-pay (WTP) thresholds. CONCLUSION: Evidence suggests that bevacizumab remains the most cost-effective first-line treatment compared to aflibercept and ranibizumab where permitted. Newer agents such as faricimab show promising cost and efficacy profiles, suggesting potential for more sustainable DME management.
Prevalence of substances with OATP1B1 inhibitory properties in individual case safety reports of suspected statin-associated myopathy - an analysis of Swiss pharmacovigilance data.
Stäuble CK, Toma V, Stammschulte T … +2 more , Allemann SS, Meyer Zu Schwabedissen HE
Eur J Clin Pharmacol · 2026 Feb · PMID 41731198 · Full text
PURPOSE: Statin associated musculoskeletal symptoms (SAMS) are common adverse drug reactions reported by 20% of statin users and are assumed to be dose dependent. The organic anion transporting polypeptide 1B1 (OATP1B1),...
PURPOSE: Statin associated musculoskeletal symptoms (SAMS) are common adverse drug reactions reported by 20% of statin users and are assumed to be dose dependent. The organic anion transporting polypeptide 1B1 (OATP1B1), a hepatocellular uptake transporter, modulates the systemic exposure of statins. The concurrent use of OATP1B1 inhibitors can increase systemic statin exposure and thus increase the risk of SAMS. METHODS: Individual case safety reports (ICSRs) of suspected adverse drug reactions (ADRs), like SAMS, are an important data source to monitor the safety of marketed drugs. We used the Swissmedic database to analyse the prevalence of potential OATP1B1 involving interactions in cases of suspected SAMS. RESULTS: In 54% of the ICSRs analysed, at least one substance with OATP1B1 inhibiting properties was used together with a statin. Antidiabetic and cardiovascular drugs were the most commonly reported substances with OATP1B1 inhibiting properties. CONCLUSION: Our findings could indicate clinically relevant OATP1B1 involving interactions in SAMS, which should be further investigated.
Clinical pharmacology of antiplatelet drugs: implications for personalized therapy.
Wichaiyo S
Eur J Clin Pharmacol · 2026 Feb · PMID 41731149 · Publisher ↗
PURPOSE: This review describes the pharmacodynamics and pharmacokinetics of currently available antiplatelet drugs, with an emphasis on implications for personalized therapy. METHODS: Scientific literature published betw...
PURPOSE: This review describes the pharmacodynamics and pharmacokinetics of currently available antiplatelet drugs, with an emphasis on implications for personalized therapy. METHODS: Scientific literature published between January 1985 and December 2025 was collected from electronic databases. Primary research papers, reviews, and clinical practice guideline articles were included for discussion. RESULTS: Aspirin and thienopyridine-type adenosine diphosphate (ADP) receptor antagonists (clopidogrel and ticlopidine) irreversibly inhibit their targets throughout the platelet lifespan, but daily dosing is required to inhibit newly formed platelets. In addition, clopidogrel bioactivity is affected by polymorphisms and interactions with cytochrome P450 2C19; while ticlopidine is rarely used due to serious side effects, such as blood dyscrasia. Newer ADP receptor antagonists (prasugrel, ticagrelor, and cangrelor) are more potent than clopidogrel and ticlopidine. Both high-dose aspirin and ADP receptor antagonists are recommended in acute settings, such as acute coronary syndrome (ACS) with percutaneous coronary intervention (PCI) and acute ischemic stroke, because they are associated with more rapid and potent antiplatelet activity. Moreover, recent evidence based on clinical and pharmacological data suggests that optimization of dual antiplatelet therapy (DAPT) with aspirin and ADP receptor antagonists can enable more effective management of thrombosis. Phosphodiesterase inhibitors (cilostazol and dipyridamole) are weaker antiplatelets that are used in combination with aspirin or clopidogrel in secondary stroke prevention. Glycoprotein IIb/IIIa inhibitors might be considered as adjunct therapy in ACS patients undergoing PCI who present with large thrombus burden. Vorapaxar is a thrombin receptor antagonist; and its slow receptor dissociation rate, coupled with a very long plasma half-life, might increase bleeding risk and limit its clinical use. CONCLUSION: Overall, the pharmacodynamics and pharmacokinetics of antiplatelets strongly support development of personalized antiplatelet therapy to achieve therapeutic outcomes and minimize the risks of unwanted effects.
Correction to: A real-world pharmacovigilance study of adverse events associated with esketamine: disproportionality analysis and detection of potential drug-drug interaction signals.
Pisanu C, Imai S, Tsuchiya M … +5 more , Inoue M, Ikegami K, Zammarchi G, Kizaki H, Hori S
Eur J Clin Pharmacol · 2026 Feb · PMID 41724879 · Full text
Abstract loading — click title to view on PubMed.
Exploring potential biomarkers and constructing prediction models of osimertinib based on a retrospective study.
Cui L, Tang M, Liang S … +5 more , Bu C, Yun Y, Gao S, Wang Z, Tao X
Eur J Clin Pharmacol · 2026 Feb · PMID 41724848 · Publisher ↗
PURPOSE: This study aimed to identify potential biomarkers for adverse reactions (ADRs) and efficacy of osimertinib, and to construct prediction models in patients with non-small cell lung cancer(NSCLC). METHODS: NSCLC p...
PURPOSE: This study aimed to identify potential biomarkers for adverse reactions (ADRs) and efficacy of osimertinib, and to construct prediction models in patients with non-small cell lung cancer(NSCLC). METHODS: NSCLC patients treated with osimertinib were retrospectively enrolled from January 2021 to July 2022. Their clinical characteristics, ADRs and prognostic outcomes (e.g., progression-free survival, objective response rate) were extracted from medical records. Univariate and multivariate analysis were performed on baseline data to identify potential biomarkers associated with ADRs and efficacy. Prediction models were constructed and validated using logistic regression. All analysis were conducted with SPSS 19.0 and Graphpad Prism 8.0. RESULTS: A total of 90 patients in training cohort and 74 patients in the validation cohort were enrolled. Univariate analysis revealed that drinking history, total bilirubin(TB), indirect bilirubin(I-Bil), and aspartate aminotransferase(AST) were potential biomarkers for ADRs. Multivariate analysis identified drinking history, TB, and AST as key predictors of severe ADRs. No variate was associated with efficacy. A prediction model for severe ADRs was established using logistic regression: y= -2.714×(drinking history) − 0.4×(TB) − 0.099×(AST) + 6.196 [Area Under the Curve (AUC) = 0.87; 95% confidence interval (CI): 0.752–0.995; P < 0.001; sensitivity: 90%; specificity: 82.5%; optimal Youden index: 0.725]. Validation of this model in 74 NSCLC patients showed a sensitivity of 83.3% and specificity of 98.2%. CONCLUSION: This study developed and validated a prediction model for severe osimertinib-related ADRs in NSCLC patients based on baseline characteristics. The model exhibits good predictive performance for severe osimertinib-related ADRs and may facilitate individualized osimertinib therapy in clinical practice.
Sexual dysfunction associated with selective serotonin reuptake inhibitors in adults with depression: a systematic review and meta-analysis.
Dagostin Ferraz S, Kuyunga L, Rech P … +7 more , Rodrigues Uggioni ML, Rodrigues Candido AC, Dagostin VS, Silva FR, Colonetti T, Grande AJ, da Rosa MI
Eur J Clin Pharmacol · 2026 Feb · PMID 41721013 · Full text
OBJECTIVE: To systematically evaluate the impact of SSRIs on sexual function in adults with depression compared to placebo through a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: A...
OBJECTIVE: To systematically evaluate the impact of SSRIs on sexual function in adults with depression compared to placebo through a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: A systematic search using the terms “sexual dysfunction”, “depression” and “antidepressant” was conducted in PubMed/MEDLINE, LILACS, Embase, and the Cochrane Library for RCTs published up to June 2025. No language restrictions were applied. Both dichotomous and continuous outcomes were analyzed with 95% confidence intervals using RevMan 5.4. The risk of bias in individual studies was assessed independently by two reviewers using the revised Cochrane Risk of Bias tool for randomized trials (RoB 2). RESULTS: Thirteen RCTs met inclusion criteria for qualitative synthesis and six were included in meta-analyses. SSRIs were significantly associated with increased risk of orgasmic dysfunction (RR = 3.28, (95% CI of 2.33 to 4.60, p < 0.00001; I² = 8%,) and reduced sexual satisfaction (RR = 1.21, (95% CI of 1.11 to 1.32, p = 0.0001, I² = 0%,). A non-significant trend toward decreased sexual desire was observed (RR = 1.40, 95% CI: 0.92–2.12, p = 0.12; I² = 54%,). No significant differences were detected in total CSFQ scores compared with placebo. CONCLUSION: SSRI use is consistently associated with sexual dysfunction, particularly orgasmic dysfunction and reduced sexual satisfaction. The GRADE assessment indicated high to moderate certainty of evidence. Orgasmic dysfunction showed high certainty, with concerns limited to risk of bias. Sexual satisfaction, sexual desire disorders, and CSFQ total scores demonstrated moderate certainty, mainly due to risk-of-bias issues.
Selective oestrogen receptor modulators and Alzheimer´s disease: a real-world pharmacovigilance study.
Yuste MT, Badillo E, Galecio JS … +1 more , Marín P
Eur J Clin Pharmacol · 2026 Feb · PMID 41703146 · Full text
PURPOSE: Selective oestrogen receptor modulators (SERMs) are a standard treatment for breast cancer and osteoporosis. Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is a serious public health c...
PURPOSE: Selective oestrogen receptor modulators (SERMs) are a standard treatment for breast cancer and osteoporosis. Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is a serious public health concern. This study aimed to identify potential pharmacovigilance signals related to dementia and AD for SERMs in menopausal and postmenopausal women. METHODS: To investigate this possible association, a disproportionality analysis was performed in VigiBase, the World Health Organization’s (WHO) global database of individual case safety reports (ICSRs). Disproportionality was quantified using the reporting odds ratio (ROR). RESULTS: We found risk of reporting dementia for tamoxifen [ROR = 1.74 (1.23–2.45)] and raloxifene [ROR = 1.63 (1.05–2.53)] and AD for raloxifene [ROR = 5.12 (3.26–8.05)]. No statistically significant association was detected for fulvestrant and bazedoxifene with dementia or AD. Most of the reports were severe and affected women over the age of 75. The latency of the reactions was predominantly long, suggesting that dementia is a late-onset reaction. The duration of treatment varied from a few months to more than three years, which may indicate that long-term exposure to SERMs is not necessary to develop dementia associated with these drugs. CONCLUSION: Signals of disproportionate reporting have been observed between the incidence of dementia and AD with SERMs. There are conflicting results from the different studies that have been conducted on the relationship between these drugs and AD. More research is needed to find out what factors determine the risk of cognitive impairment associated with SERMs.
Levetiracetam in critically ill patients with augmented renal clearance: a systematic review.
Fernández Varela AM, Ramudo Cela L
Eur J Clin Pharmacol · 2026 Feb · PMID 41688794 · Publisher ↗
PURPOSE: Levetiracetam, a second-generation antiepileptic drug, is predominantly eliminated renally, and its clearance is closely linked to creatinine clearance (CrCl). In critically ill patients with augmented renal cle...
PURPOSE: Levetiracetam, a second-generation antiepileptic drug, is predominantly eliminated renally, and its clearance is closely linked to creatinine clearance (CrCl). In critically ill patients with augmented renal clearance (ARC), defined as CrCl > 130 mL/min/1,73 m², levetiracetam elimination is accelerated, potentially resulting in subtherapeutic plasma concentrations when standard doses (500–1500 mg/12 h) are used. This study systematically reviewed the pharmacokinetics of levetiracetam in critically ill patients with ARC to inform alternative dosing strategies. METHODS: A systematic review of the literature was conducted using PubMed and Embase up to July 2024. The search terms included “levetiracetam,” “pharmacokinetics,” and “pharmacokinetic*,” utilizing both free-text and controlled vocabulary approaches. The PRISMA 2020 methodology guided the study selection and analysis. RESULTS: From 1612 initial records, seven studies comprising 110 patients met the inclusion criteria. The prevalence of ARC within the pooled patient cohort from the included studies was 52.7%, and the CrCl values ranged from 54 to 244 mL/min. The findings suggest that standard levetiracetam doses may be insufficient in critically ill patients with ARC. Simulations indicate that many patients might require higher doses or alternative regimens (e.g., prolonged infusions or doses exceeding 6 g/day) to achieve therapeutic plasma concentrations, although clinical data confirming efficacy at these high doses are limited. CONCLUSION: This review underscores the potential need for tailored levetiracetam dosing guidelines for patients with ARC. However, given the variability in therapeutic targets and limited data on patients with extreme ARC, further research is essential to validate optimal dosing strategies before standardized protocols can be established. The protocol for this systematic review was registered in PROSPERO (CRD420251246297).
Dynamics of long-term adherence to lipid-lowering therapy in patients after myocardial infarction.
Hagström E, Ortsäter G, Almlöf E … +5 more , Vasilevska M, Leósdóttir M, Wettermark B, Banefelt J, Larsen AP
Eur J Clin Pharmacol · 2026 Feb · PMID 41667683 · Publisher ↗
Despite recommendations to use oral lipid-lowering therapies (LLT) in secondary prevention of atherosclerotic cardiovascular disease, numerous studies have shown substantial under-utilization. We assessed long-term persi...
Despite recommendations to use oral lipid-lowering therapies (LLT) in secondary prevention of atherosclerotic cardiovascular disease, numerous studies have shown substantial under-utilization. We assessed long-term persistence and dynamics of adherence to oral LLTs in patients after their first ever myocardial infarction (MI) in Sweden. A total of 83,407 patients with a MI (2010–2017) and who were dispensed an oral LLT were identified through Swedish nationwide health registries. After one, three and eight years of follow-up, persistence to lipid-lowering therapies was 90.3%, 71.1% and 50.8%, respectively. Adherence, quantified using the proportion of days covered (PDC), was a highly dynamic phenomenon with patients frequently moving between categories (high, medium, and low) of adherence. Adherence was high among persistent patients (> 70% had PDC ≥ 80%), but only 30% regained high adherence following non-persistence. Higher age, prescription from primary care, and higher income were associated with lower risk of non-persistence whereas higher comorbidity index, no prior statin use and concomitant use of platelet inhibitors were associated with increased risk. This study highlights the dynamic nature of adherence at the patient-level and that particular focus on adherence may be needed following non-persistence. Socioeconomic and clinical factors associated with non-persistence were identified, which in turn may help target measures to improve adherence in this high-risk patient group.
Comparative efficacy of levosimendan and dobutamine in sepsis-related cardiac impairment: a meta-analysis.
Liu X, Shaibu Z, Huang X … +2 more , Wang D, Zhu W
Eur J Clin Pharmacol · 2026 Feb · PMID 41665777 · Publisher ↗
BACKGROUND: Sepsis-induced cardiac dysfunction significantly impacts patient outcomes, with inotropic support playing a crucial role in management. Levosimendan and dobutamine are commonly used, but their comparative eff...
BACKGROUND: Sepsis-induced cardiac dysfunction significantly impacts patient outcomes, with inotropic support playing a crucial role in management. Levosimendan and dobutamine are commonly used, but their comparative efficacy remains debated. This meta-analysis evaluates the efficacy and safety of levosimendan versus dobutamine in sepsis-related cardiac impairment, focusing on mortality, intensive care unit (ICU) outcomes, and infection risks. METHODS: We systematically analyzed randomized controlled trials (RCTs) comparing levosimendan and dobutamine in septic patients with cardiac dysfunction. Primary outcomes included mortality and ICU length of stay, while secondary outcomes assessed pneumonia, peritonitis, and urinary tract infection (UTI) risks. Model selection for pooled odds ratios (OR) or mean differences (MD) with 95% confidence intervals (CI) was based on heterogeneity, employing random-effects models for substantial heterogeneity (I² > 50%) and fixed-effects models otherwise. Meta-analyses were performed using Rev-Man 5.4. STUDY REGISTRATION: Prospero ID (CRD420261283881). RESULTS: The meta-analysis included 9 RCTs (n = 289 patients) in total. For mortality, data were available from 8 RCTs (n = 239 patients), revealing no significant reduction with levosimendan compared to dobutamine (OR: 0.89, 95% CI: 0.52-1.54, P = 0.68; I²=0%). For ICU length of stay, 7 RCTs (n = 241 patients) were included, showing no significant difference (MD - 2.02 days, 95% CI - 6.44 to 2.39; P = 0.37; I²=83%). Regarding hospital-acquired infections, pneumonia was analyzed in 5 RCTs (n = 143 patients) (OR: 1.05, 95% CI: 0.48-2.29, P = 0.90; I²=0%), peritonitis in 3 RCTs (n = 98 patients) (OR 1.56, 95% CI 0.62-3.95; P = 0.35; I²=0%), and urinary tract infections in 3 RCTs (n = 91 patients) (OR: 0.70, 95% CI: 0.17-2.81, P = 0.61; I²=0%). CONCLUSION: Current evidence indicates that levosimendan does not reduce mortality or ICU length of stay compared to dobutamine in sepsis-induced cardiac dysfunction, and infection risks are comparable. The high heterogeneity in ICU outcomes warrants cautious interpretation. These findings do not support the routine preferential use of levosimendan over dobutamine. Larger, well-designed trials are needed to identify specific patient subgroups that may benefit from levosimendan.
The use of generic versus brand names in (clinical) pharmacology education across Europe: a cross-sectional survey.
Slezáková V, Rychlíčková J, Cazaubon Y … +12 more , Donker EM, van Leeuwen E, Likic R, Mazánková D, Piët JD, De Ponti F, Raasch W, van Rosse F, Sanz EJ, Schwaninger M, van Agtmael MA, Tichelaar J
Eur J Clin Pharmacol · 2026 Feb · PMID 41663722 · Full text
PURPOSE: In pharmacology and clinical pharmacology (P&CP) teaching, using generic names of medicines contributes to global comprehensibility. However, brand names are often used in routine clinical practice, which may po...
PURPOSE: In pharmacology and clinical pharmacology (P&CP) teaching, using generic names of medicines contributes to global comprehensibility. However, brand names are often used in routine clinical practice, which may pose a challenge in the educational setting. This study aimed to explore P&CP teachers’ use of and attitudes towards generic and brand names in undergraduate education, as well as national prescription regulations. METHODS: A survey was conducted with P&CP teachers from 38 European countries. An electronic questionnaire was used to collect data on the participants’ profiles, the nomenclature used and preferred in undergraduate education, and prescribing practices. The latter were then verified with national regulatory authorities. RESULTS: Sixty-one teachers from 23 countries participated in the study, the majority being physicians (n = 47). In total, 13 (21%) teachers use only generic names in their teaching, while 46 (75%) use both generic and brand names. Thirty-four (56%) teachers preferred listing brand names in case-based teaching, as this reflects real life. Conversely, 37 (61%) teachers stated that students should not be exposed to brand names before graduation. Generic prescribing is either allowed or mandatory in all participating countries except two, where brand-name prescribing is mandatory. CONCLUSION: This study shows that generic names must remain fundamental in P&CP education, but brand names also play a role, especially in case-based education, reflecting real-life practice. Potential implications of generic and brand prescribing for internationalisation in education could be worth further attention.
Association between magnesium sulfate administration and mortality in critically ill patients with sepsis-associated acute kidney injury: a retrospective propensity score-matched cohort study.
Duan XJ, Lan JR, Zhu MG … +4 more , Chen JL, Zhang CY, Yin HY, Gu WJ
Eur J Clin Pharmacol · 2026 Feb · PMID 41661337 · Publisher ↗
PURPOSE: The effect of magnesium sulfate on long-term outcomes in patients with sepsis-associated acute kidney injury (SA-AKI) remains unknown. This study aimed to evaluate its association with long-term mortality in SA-...
PURPOSE: The effect of magnesium sulfate on long-term outcomes in patients with sepsis-associated acute kidney injury (SA-AKI) remains unknown. This study aimed to evaluate its association with long-term mortality in SA-AKI patients. METHODS: We retrospectively analyzed data on patients with SA-AKI from the Medical Information Mart for Intensive Care-IV database. Magnesium sulfate administration after SA-AKI onset was defined as the exposure. Patients were matched 1:1 using propensity score matching (PSM). The primary endpoint was 1-year mortality; secondary endpoints included ICU mortality, in-hospital mortality, 28-day mortality, and major adverse kidney events within 30 days (MAKE30). Associations were assessed using multivariable analyses to calculate hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Among 16,156 patients, 13,672 received magnesium sulfate. After PSM, 4936 patients (2468 per group) were included. In the PSM cohort, 1-year mortality was lower in the magnesium sulfate group than in the non-use group (41.21% vs. 47.41%; P < 0.001). Magnesium sulfate administration was significantly associated with reduced 1-year mortality (HR, 0.77; 95% CI, 0.71–0.84; P < 0.001), consistent across all subgroup. MAKE30 incidence was also lower in the magnesium sulfate group (33.14% vs. 38.41%; P < 0.001), with a significant associated (OR, 0.83; 95% CI, 0.73–0.94; P = 0.004). Additionally, magnesium sulfate was associated with reduced ICU mortality, in-hospital mortality, and 28-day mortality. Sensitivity analysis performed in the original cohort also demonstrated similar results. CONCLUSION: Magnesium sulfate administration was associated with reduced long-term mortality in SA-AKI patients. These findings warrant confirmation through randomized controlled trials.
Bleeding risk of rivaroxaban and edoxaban with and without amiodarone in atrial fibrillation patients: a prospective cohort study.
Wang Z, Yang F, Wang Q … +2 more , Xia X, Lv Q
Eur J Clin Pharmacol · 2026 Feb · PMID 41661331 · Publisher ↗
BACKGROUND: Rivaroxaban and edoxaban are commonly used for stroke prevention in patients with atrial fibrillation (AF). This study aimed to compare the bleeding risk between rivaroxaban and edoxaban in patients with atri...
BACKGROUND: Rivaroxaban and edoxaban are commonly used for stroke prevention in patients with atrial fibrillation (AF). This study aimed to compare the bleeding risk between rivaroxaban and edoxaban in patients with atrial fibrillation, both with and without the combination of amiodarone. METHODS: In this prospective cohort study, participants were divided into four groups: rivaroxaban monotherapy, edoxaban monotherapy, rivaroxaban combined with amiodarone, and edoxaban combined with amiodarone. Propensity score matching (PSM) was used to control for confounding factors. The primary endpoint was the time to the first occurrence of bleeding (major, CRNM, or minor). RESULTS: A total of 910 patients were included. The bleeding risk was similar between the rivaroxaban (9.0%) and edoxaban (13.5%) monotherapy groups (P = 0.403). However, the bleeding risk in the rivaroxaban-amiodarone group was significantly higher than in the edoxaban-amiodarone group in the PSM analysis (HR = 2.015, 95% CI = 1.026–3.958, P = 0.042). Patients receiving standard-dose rivaroxaban with amiodarone had a significantly higher bleeding risk than those receiving edoxaban with amiodarone (HR = 2.678, 95% CI = 1.017–7.045, P = 0.046). Additionally, rivaroxaban with amiodarone was associated with a significantly higher bleeding risk compared to edoxaban with amiodarone in patients with renal dysfunction (HR = 2.186, 95% CI = 1.016–4.702, P = 0.045). CONCLUSION: When combined with amiodarone, rivaroxaban was associated with a higher bleeding risk compared to edoxaban, particularly in patients receiving the standard dose of anticoagulants or with impaired renal function. This study the name of the trial register: Zhongshan Hospital, Fudan University, Registration number: ChiCTR2200062662, Date of Registration: 2022-08-15.
CYP2C19 genotyping and mavacamten: predicting outcomes in normal, intermediate and rapid metabolisers in obstructive hypertrophic cardiomyopathy.
Kasolo Y, Burford E, Obeidat M … +5 more , Beaman GM, Monk T, Bastiaenen R, Newman WG, Cooper RM
Eur J Clin Pharmacol · 2026 Feb · PMID 41649583 · Full text
PURPOSE: Mavacamten is the first targeted therapy for obstructive hypertrophic cardiomyopathy (oHCM). It is metabolised via cytochrome p450 enzymes, with variations in the CYP2C19 gene having predominant influence on pla...
PURPOSE: Mavacamten is the first targeted therapy for obstructive hypertrophic cardiomyopathy (oHCM). It is metabolised via cytochrome p450 enzymes, with variations in the CYP2C19 gene having predominant influence on plasma concentrations of mavacamten. We aimed to outline the effect of CYP2C19 metaboliser status on outcomes in patients taking mavacamten. METHODS: We retrospectively analysed clinical and echocardiographic data in patients with symptomatic oHCM taking mavacamten. CYP2C19 genotyping was undertaken by loop-mediated isothermal amplification (LAMP) on EDTA whole blood (LaCAR MDx, Liege Belgium) followed by Sanger sequencing of the coding exons of CYP2C19. Logistical regression was used to assess time taken to optimisation. RESULTS: Fifty-five patients (59±13 years; 73% male) were included. Genotyping of CYP2C19*2, CYP2C19*3, and CYP2C19*17 alleles was conducted. Due to low numbers in the ultrarapid (n = 1) and poor (n = 2) groups, statistical analysis was performed in intermediate, normal and rapid metabolisers. Using normal metabolisers as the reference, there was a non-significant trend towards faster optimisation in intermediate metabolisers (odds ratio 0.63 [95% CI: 0.12–3.19]) and rapid metabolisers (OR 0.55 [95% CI: 0.11–2.53]). While reductions in peak resting (40 ± 34.37 mmHg) and Valsalva (64 ± 35.23 mmHg) left ventricular outflow tract gradients were statistically significant across the cohort (p < 0.0001), there was no interaction between differing CYP2C19 groups and time (p = 0.69). CONCLUSION: Excluding poor metabolisers, variations in the CYP2C19 gene do not explain different clinical outcomes in patients with oHCM on mavacamten. Beyond genotyping of the targeted variants, CYP2C19 sequencing did not provide any additional clinically relevant information.
Clopidogrel versus aspirin monotherapy following dual antiplatelet therapy after percutaneous coronary intervention: an updated meta-analysis of 162,829 patients.
Elbahloul MA, Mansour A, Galal A … +5 more , Moawad WM, Khaled M, Kasem AW, Labeeb EE, Elgendy IY
Eur J Clin Pharmacol · 2026 Feb · PMID 41649579 · Full text
BACKGROUND: Dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) remains a cornerstone for preventing ischemic events; however, the optimal long-term single antiplatelet therapy after compl...
BACKGROUND: Dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) remains a cornerstone for preventing ischemic events; however, the optimal long-term single antiplatelet therapy after completion of DAPT remains unclear. We aimed to compare clopidogrel and aspirin monotherapy after completion of the standard duration of DAPT. METHODS: A systematic search was conducted on PubMed, Scopus, Cochrane Library, and Web of Science from inception to April 2025. We included randomized clinical trials and observational studies that compared aspirin versus clopidogrel monotherapy after completion of standard-duration DAPT. The primary and co-primary outcomes were major adverse cardiovascular events (MACE) and major bleeding, respectively. Using random-effects models, outcomes were expressed as risk ratios (RR) or hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Ten studies, comprising 162,829 patients, were included. Clopidogrel was significantly associated with a lower risk of MACE (HR: 0.72, 95% CI: 0.66–0.79) and net adverse clinical events (NACE) (RR: 0.86, 95% CI: 0.73–0.99) at a weighted mean follow-up of 3.2 years. Major bleeding showed no significant difference between clopidogrel and aspirin (RR: 0.85, 95% CI: 0.60–1.21). Moreover, there was no difference between clopidogrel and aspirin in all-cause mortality, myocardial infarction, revascularization, stroke, or all bleeding. CONCLUSION: Among patients who underwent PCI, clopidogrel monotherapy after standard DAPT was associated with a lower incidence of MACE and NACE compared with aspirin monotherapy, without increasing the bleeding risk.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe