fimasartan + rosuvastatin (Tubero / Tuvero)

Suspected Rosuvastatin-Associated Bullous Pemphigoid: A Diagnostic and Therapeutic Challenge.

Gandhi Shirley S, Clark Barrie B, Ashraf Iman I, Qadir Nadim N et al.

Effect of rosuvastatin and ezetimibe therapy on LDL-cholesterol reduction and non-invasive arterial injury markers in children with heterozygous familial hypercholesterolemia: a prospective, open-label, randomized study.

Skarlovnik Ajda A, Gorjanc Tevz T, Sikonja Jaka J, Kafol Jan J et al.

Individuals with familial hypercholesterolemia (FH) require early lipid-lowering therapy (LLT). We compared rosuvastatin versus ezetimibe treatment and the role of major non-invasive arterial injury markers in children with heterozygous FH. In this prospective, open-label, randomized study, 45 children with FH [median age 10.5 years (IQR 8.7-14.5)] received rosuvastatin 5 mg OD or ezetimibe 10 mg OD for 6.2 months. Carotid intima-media thickness (cIMT), reactive hyperemia index (RHI), pulse wave velocity (PWV), and beta stiffness were evaluated in relation to anthropometric and lipid-related variables. Rosuvastatin produced a greater LDL-C reduction than ezetimibe (36.7% vs. 18.3%; p < 0.001) with 9/20 (45%) children achieving LDL-C <3.5 mmol/L compared to 2/15 (13%) in ezetimibe group. No reports of myalgias, elevations in transaminases, or creatine kinase (CK) were observed in any of the groups. Markers at baseline correlated mainly with age and anthropometry. Beta stiffness decreased during LLT in the overall cohort (-0.24; 95% CI -0.51 to -0.03, p = 0.002) and in the rosuvastatin group (-0.4; 95% CI -0.7 to -0.1, p = 0.028), with no between-group difference (p = 0.266). This likely reflects regression to the mean, as LDL-C reduction and treatment allocation had only small effects across all markers. Rosuvastatin achieved greater LDL-C reduction than ezetimibe in children with FH, without difference in safety and tolerability profiles. Arterial injury markers correlated mainly with age and anthropometry, and their short-term changes were not treatment-related, likely due to limited power and the short follow-up.

Food-associated pharmacokinetic differences and variability of a rosuvastatin/ezetimibe fixed-dose combination in replicated bioequivalence studies.

Liu Xingwei X, Bai Lu L, Li Qian Q, Fu Yingli Y et al.

Rosuvastatin/ezetimibe fixed-dose combinations target cholesterol synthesis and intestinal absorption, but pharmacokinetics may differ by analyte, endpoint, and fasted/fed state. This study characterized food-associated pharmacokinetic differences, reference-product within-subject variability, and bioequivalence decision pathways. Data were integrated from two independently conducted, single-center, randomized, open-label, single-dose, two-sequence, four-period, fully replicated crossover bioequivalence trial parts in healthy Chinese adults (ChiCTR2500110429). Free and total ezetimibe and rosuvastatin were evaluated in fasted and fed states. Bioequivalence was assessed separately in each trial part, while exploratory food-associated comparisons used reference-product data averaged across replicated periods within participants. Food-associated patterns differed by analyte and endpoint. Fed-to-fasted geometric mean ratios (GMRs) for free ezetimibe were 258.8% for maximum plasma concentration (Cmax), 125.9% for area under the concentration-time curve from time zero to the last measurable concentration (AUC0-t), and 127.1% for area under the concentration-time curve from time zero to infinity (AUC0-∞). For total ezetimibe, the Cmax GMR was 152.4%, whereas AUC shifts were smaller than the free ezetimibe. Rosuvastatin GMRs were 47.7%, 59.2%, and 60.8% for Cmax, AUC0-t, and AUC0-∞, respectively. Within-subject coefficients of variation (CVW%) differed by analyte, endpoint, and state. All primary endpoints met average bioequivalence (ABE) or reference-scaled average bioequivalence (RSABE) criteria in both states. No serious or grade ≥ 2 adverse events or adverse-event-related withdrawals occurred. Food-associated pharmacokinetic differences were analyte- and endpoint-dependent, whereas formal bioequivalence was demonstrated in both states. These findings support separate interpretation of food-associated pharmacokinetics, reference-product variability, and bioequivalence in multi-analyte fixed-dose combination evaluation.

Efficacy and safety of PCSK9 inhibitors combined with statins in acute ischemic stroke: a systematic review and meta-analysis.

Lin Xiaozuo X, He Rongxin R, Zhang Xiaohan X, Zeng Yinan Y et al.

Acute ischemic stroke (AIS) imposes a substantial global burden of mortality and long-term disability. As novel lipid-modulating agents, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have demonstrated therapeutic benefits across a wide range of cardiovascular patient groups, but dedicated evidence in AIS cohorts has not been quantitatively synthesized. We therefore conducted this meta-analysis to compare the efficacy and safety of PCSK9i combined with statin therapy versus statin monotherapy among patients with AIS. We searched seven databases from inception to May 31, 2026 for randomized controlled trials (RCTs). Two reviewers independently performed study screening, data extraction, and risk-of-bias assessment. Dichotomous and continuous outcomes were synthesized using odds ratios (OR) and mean differences (MD), respectively. Heterogeneity was assessed via the I2 statistic and Cochran's Q test, with leave-one-out sensitivity analysis and model switching to explore heterogeneity and test robustness. We evaluated the certainty of evidence using the GRADE approach. Compared with statin monotherapy, PCSK9i combination therapy significantly improved functional independence (modified Rankin Scale (mRS) 0-2: OR = 2.17, 95% CI 1.29-3.64, P = 0.003, I2 = 48%) and reduced recurrent ischemic stroke risk (OR = 0.33, 95% CI 0.16-0.69, P = 0.003, I2 = 0%). LDL-C was substantially reduced in the combination group (MD = 0.66 mmol/L, 95% CI 0.45-0.87, P < 0.00001), with high heterogeneity (I2 = 86%) partially explained by statin type (atorvastatin vs. rosuvastatin, P = 0.02). No significant difference was observed in National Institutes of Health Stroke Scale (NIHSS) scores (MD = 2.38, 95% CI - 0.63 to 5.39, P = 0.12, I2 = 98%), with heterogeneity largely driven by one study. Safety outcomes, including abnormal liver function (OR = 0.67, 95% CI 0.35-1.28, P = 0.22), major adverse cardiovascular events(MACE) (OR = 0.56, 95% CI 0.18-1.75, P = 0.32), and total adverse events (OR = 0.85, 95% CI 0.49-1.45, P = 0.54), were comparable between groups. According to the GRADE assessment, evidence certainty was moderate for mRS, low for recurrent stroke, LDL-C, and safety outcomes, and very low for NIHSS. PCSK9i adjunctive therapy may improve functional recovery and reduce stroke recurrence in AIS patients receiving statins, with acceptable short-term safety; however, the current evidence remains preliminary and requires confirmation in larger, adequately powered randomized trials.