Background/Objectives: Conventional SeDeM-ODT screening relies on physicochemical properties and endpoint disintegration tests, which may have limited discriminatory power among formulations that already meet pharmacopoeial disintegration requirements. This study aimed to extend SeDeM-ODT by incorporating texture analyzer-derived descriptors of low-volume liquid disintegration behavior. Methods: Bisoprolol fumarate was used as a low-dose model drug. Selected excipients were characterized using SeDeM and conventional SeDeM-ODT approaches. Texture analyzer distance-time profiles were used to derive swelling efficiency (SE), residue height (RH), and structural transition efficiency (STE), which were converted into SeDeM-compatible parameters. Orodispersible tablets were developed using a two-factor central composite design and evaluated for mechanical properties, pharmacopoeial disintegration, comparative dissolution performance, texture analyzer behavior, and supportive Heckel parameters. Results: All formulations met the pharmacopoeial disintegration criteria and showed rapid drug release under the applied dissolution conditions. Conventional endpoint-based responses showed limited discriminatory value within the investigated formulation space. In contrast, SE, RH, and STE differentiated formulation-dependent swelling, residual structural persistence, and transition toward structural collapse under low-volume liquid controlled-force conditions. MCC-rich formulations generally retained greater residual structure, whereas lactose-rich and/or higher-superdisintegrant formulations showed lower residual persistence. Comparative kinetic fitting and Heckel analysis supported these interpretations but did not independently establish a definitive disintegration mechanism. Conclusions: Incorporating low-volume liquid texture analyzer-derived parameters into SeDeM-ODT improved the comparative interpretation of excipient and formulation behavior. These findings suggest that pharmacopoeial disintegration compliance may coexist with distinct structural pathways not fully captured by conventional endpoints.

Background/Objectives: The global rise in obesity-related hypertension, metabolic syndrome, and chronic inflammation calls for a precise characterization of the safety profiles of first-line therapies. While amlodipine is considered metabolically neutral, its real-world impact on dysglycemia and inflammatory biomarkers remains incompletely defined. This study aims to characterize the metabolic and inflammatory adverse drug reaction profile of amlodipine, using the EudraVigilance database. Methods: Descriptive and disproportionality analyses were performed on 41,872 Individual Case Safety Reports recorded prior to 17 May 2026. Amlodipine was compared against major antihypertensive classes (beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, sartans, and diuretics), calculating reporting odds ratios (ROR) and 95% confidence intervals. Results: "Hyperglycaemia" could be considered a safety signal for amlodipine, compared to beta-blockers (e.g., bisoprolol-ROR: 2.56), ACE inhibitors (e.g., ramipril-ROR: 2.82), and sartans (e.g., candesartan-ROR: 3.85). "Metabolic syndrome" was reported for amlodipine with a lower probability than for hydrochlorothiazide (ROR: 0.35). Inflammatory signals (e.g., increased C-reactive protein) appeared less frequently for amlodipine than for certain renin-angiotensin-aldosterone system inhibitors (e.g., perindopril-ROR: 0.53). Conclusions: The disproportionality analysis identified relatively lower reporting frequencies for several metabolic and inflammatory adverse drug reactions, compared with selected antihypertensive agents. These findings represent pharmacovigilance signals that warrant further investigation in analytical epidemiological and clinical studies. Although hyperglycemia was reported disproportionally relative to several comparator drugs, reports of T2DM were less frequently reported for amlodipine. However, these observations should not be interpreted as evidence of differences in clinical risk, because disproportionality analyses cannot establish incidence or causality. Reports of inflammation likely reflect patient comorbidities rather than a direct drug effect. These findings demonstrate that post-marketing surveillance remains essential, even when accounting for the methodological limitations of spontaneous reporting.

Background: Beta-blockers (BBs) remain a foundation of cardiovascular therapy. However, cumulative evidence suggests that metabolic adverse effects may differ significantly between individual sub-classes. While conventional BBs have been associated with changes in glucose and lipid metabolism, the comparative real-world reporting patterns of these events have not been comprehensively evaluated. Objective: We investigated the association between selected BBs and metabolic diseases using a large pharmacovigilance database and compared the reporting profiles of metoprolol (MET), carvedilol (CAR), bisoprolol (BIS), and nebivolol (NEB). Methods: A descriptive and disproportionality analysis was performed using Individual Case Safety Reports (ICSRs) submitted to the EudraVigilance database up to 26 April 2026. Metabolic adverse events were grouped into pathophysiological categories, including dysglycemia and type 2 diabetes mellitus (T2DM), lipid disorders, obesity-related disorders, inflammatory biomarkers, and hepatic steatosis. Reporting odds ratios (RORs) with 95% confidence intervals (CI) were calculated to identify disproportional reporting signals. To improve clinical reliability, a stratified analysis restricted to healthcare professional (HP)-submitted reports was conducted. Results: A total of 63.744 ICSRs were identified for the four BBs, including 27.169 for MET, 21.860 for BIS, 9487 for CAR, and 5228 for NEB. Dysglycemic events represented the most frequently reported metabolic category, with hyperglycemia and T2DM accounting for 155 reports each. MET was associated with the highest number of reports for T2DM, obesity, hepatic steatosis, and elevated triglycerides. In HP-submitted reports, MET showed significantly higher reporting odds of increased triglycerides, obesity, inflammation, and T2DM than BIS and/or CAR. CAR showed higher reporting odds for hyperglycemia and obesity compared with BIS, whereas BIS and, particularly, NEB presented comparatively lower reporting frequencies for metabolic diseases. No significant differences were observed for hepatic steatosis, decreased high density lipoprotein cholesterol (HDL-C), or impaired glucose tolerance. Conclusions: This large-scale pharmacovigilance study highlights substantial heterogeneity in the reporting of metabolic adverse events among commonly prescribed BBs. MET and to a lesser extent CAR were associated with higher reporting odds of metabolic diseases, whereas BIS and especially NEB demonstrated more favorable reporting profiles. Although causality cannot be established from spontaneous reporting data, these findings support individualized BB selection and closer metabolic monitoring in patients with cardiometabolic risk factors.

Acute myocardial infarction (AMI) and insomnia are mutually causal. However, therapeutic strategies for AMI combined with insomnia remain limited. Mechanistically, parachlorophenylalanine (PCPA)-induced sleep deprivation (SD) exacerbates AMI by activating the sympathetic nervous system and triggering systemic inflammatory responses. However, the specific cascade through which PCPA-induced SD-mediated systemic inflammation aggravates myocardial injury remains unclear. Bisoprolol amlodipine tablet (BAT), containing bisoprolol and amlodipine, exerts cardiovascular protective effects, in which bisoprolol mitigates sympathetic overactivation, while amlodipine alleviates AMI-related inflammatory responses. Shumian capsule (SMC) improves sleep quality with potential anti-inflammatory and neuroprotective properties. Given the complementary mechanisms of BAT and SMC, and the unmet clinical need for safe, effective therapies targeting AMI-insomnia comorbidity, this study aims to explore the therapeutic mechanisms of BAT combined with SMC on myocardial injury induced by AMI and PCPA-induced SD, providing novel insights for clinical practice. Male Sprague Dawley rats were randomly divided into five groups: sham, MI, MI + SD, BAT, and BAT + SMC. The MI model was established by ligating the left anterior descending coronary artery, and the SD model was induced by intraperitoneal injection of parachlorophenylalanine. After model establishment, rats in the BAT group received BAT (1.05 mg/kg, i.g.), and those in the BAT + SMC group received BAT combined with SMC (252 mg/kg, i.g.) for one week. Behavioral tests, echocardiography, heart rate, heart weight (HW)/body weight (BW), HW/tibia length (TL), histopathological staining, immunofluorescence co-localization, ELISA, qRT-PCR, and Western blot were used to evaluate anxiety- and depression-like behaviors, cardiac function, tissue injuries, inflammatory responses, and related gene and protein expression. PCPA-induced SD mediated the aggravation of MI-induced anxiety and depression-like behaviors, hippocampal and myocardial pathological injuries, myocardial fibrosis, apoptosis, and cardiac dysfunction in rats. It also increased the levels of myocardial injury biomarkers and inflammatory cytokines, and was accompanied by elevated activation status of the Panx1/P2X7 pathway, which may correlate with promoted neutrophil recruitment and changes in NETosis-related markers. Compared with monotherapy with BAT, the BAT combined with the SMC group showed more favorable alterations across all measured parameters. Compared with monotherapy with BAT, the combination of BAT and SMC showed more favorable alterations in all measured parameters. BAT combined with SMC improved the sucrose preference index and locomotor activity, ameliorated neuronal and dendritic injuries in the hippocampus, increased left ventricular ejection fraction and shortening fraction, reduced left ventricular end-diastolic and end-systolic diameters, HR, HW/BW, and HW/TL, alleviated myocardial fibrosis and apoptosis, decreased the levels of CK-MB, cTnI, TNF-α, and IL-1β, was correlated with suppressed expression of Panx1 and P2X7, and presented lower levels of NETosis-related markers (MPO, NE, and Cit-H3). BAT combined with SMC may alleviate myocardial injuries in rats with AMI and PCPA-induced SD via alterations to the Panx1/P2X7 pathway-associated changes in NETosis-related markers. This combined intervention integrates the cardiovascular-protective actions of BAT with the sleep-improving and neuroprotective properties of SMC, which may help relieve the vicious cycle of PCPA-induced SD-triggered inflammation and myocardial damage. Our findings reveal a molecular link between the Panx1/P2X7-associated changes in NETosis-related markers and the therapeutic benefits of BAT and SMC combination therapy, and provide preclinical evidence for its potential translation into clinical practice. This innovative treatment strategy offers a safe and effective alternative for managing AMI patients with concurrent insomnia, addressing a critical unmet medical need.

Myocarditis as the inaugural manifestation of primary Sjögren's syndrome is exceptionally rare, and its occurrence in a seronegative patient without prominent sicca features represents a particularly challenging diagnostic scenario. We report a 20-year-old woman presenting with chest pain and inflammatory polyarthralgia, in whom echocardiography revealed moderate biventricular systolic dysfunction and cardiac MRI confirmed active myocarditis fulfilling the 2018 Lake Louise criteria. In the absence of anti-SSA, anti-SSB, and ANA, the diagnosis of seronegative primary Sjögren's syndrome was established through minor salivary gland biopsy demonstrating stage III chronic sialadenitis and a positive Schirmer's test confirming objective ocular dryness, fulfilling the 2016 ACR/EULAR criteria with a total score of 4. Treatment with hydroxychloroquine, methylprednisolone, bisoprolol, and an ACE inhibitor resulted in complete myocardial recovery at 3 months, with normalization of ejection fraction and global longitudinal strain. This case highlights that in young patients with unexplained myocarditis, systematic autoimmune screening including minor salivary gland biopsy is the decisive diagnostic step when serology alone is unrevealing, and that timely diagnosis enables targeted treatment and full cardiac recovery.

G protein-coupled receptors (GPCRs) can trigger distinct signaling pathways depending on their localization. Because their appearance is not restricted, GPCRs can signal not only from the plasma membrane but also from internalized compartments. The pH of endosomes is significantly lower compared to the extracellular environment, and thus, location-biased ligands can be developed by carefully adjusting their physicochemical properties. This work describes the development of pH-sensitive β-adrenergic receptor antagonists with weak basicity, conferring enrichment in acidic compartments. Starting from FDA-approved β-blockers including bisoprolol, metoprolol, propranolol, and nebivolol, chemical synthesis, physicochemical studies, in vitro pharmacological investigations, and structure-activity relationship studies led to ligands with considerably higher potency at representative acidic pH values of 6 and 6.5 compared to a pH of 7.4, which is typical for ligand binding at the plasma membrane. Bis-fluorination in the beta position of nitrogen substituents was the most effective and led to pH-sensitive analogs of bisoprolol, metoprolol, and propranolol with 10- to 12-fold higher potencies at endosome-specific pH values. Because endosomal β-adrenergic receptors are suggested to be associated with heart hypertrophy and cardiac dysfunction, the newly developed ligands may serve as lead compounds for the development of powerful and safe cardioprotective drugs.

The intensity of gastric peristaltic motility and the rate of gastric emptying exert a substantial influence on the gastrointestinal absorption of orally administered drugs, particularly on the rate of absorption. The objective of this study was to elucidate how these factors influence drug absorption and to establish a simple framework for predicting the variability in oral drug pharmacokinetics. To minimize inter-subject confounding, this study focused on the intra-subject variability (CVintra) of the maximum plasma concentration (Cmax). Tablets of acetaminophen (AA) and bisoprolol fumarate (BP), which are Biopharmaceutics Classification System (BCS) class 1 drugs, were used as model formulations because of their high (AA: 27.61%) and low (BP: 6.38%) CVintra of Cmax in the previously reported bioequivalence (BE) studies. This framework was designed to perform repeated in silico simulations to evaluate the impact of the Gastric Interdigestive Migrating Motor Complex (gastric IMMC) phases at the time of drug administration on its plasma concentration, based on the in vitro disintegration-driven drug release rate. The drug release rate during gastric IMMC phases I-III was evaluated using a disintegration tester in vitro. In the simulation, gastric IMMC phases at the time of administration were randomly selected based on the reported phase durations. The simulated CVintra of Cmax values were 6.47% for AA and 1.22% for BP, respectively, reproducing the rank order of variabilities in the reported BE studies. Although the absolute CVintra values were underestimated by about fourfold, the results suggest that gastric motility and emptying partially contribute to the CVintra of Cmax. Sensitivity analyses further indicated that drug permeability and elimination-related pharmacokinetic parameters also influenced the magnitude of CVintra of Cmax, suggesting the importance of a relative balance between the absorption and distribution/elimination rates from the systemic circulation. This approach demonstrates the potential to predict the risk of intra-subject variability in oral absorption and may support formulation development of oral drug products by ensuring BE.

Heart failure is a major contributor to maternal morbidity and mortality. Pregnancy is a state of hemodynamic stress, and normal physiologic changes of pregnancy may mimic signs of heart failure. Prepregnancy counseling, multidisciplinary care, and referral to a center with expertise in managing pregnant patients with heart failure can help optimize outcomes. The option for abortion care should be available to all patients with heart failure, regardless of the severity of the disease, and is an essential component of individualized counseling. In this Consult, we provide guidance for managing patients with heart failure with reduced ejection fraction who are continuing pregnancy. The following are Society for Maternal-Fetal Medicine (SMFM) recommendations: (1) we recommend that all patients with right heart failure due to pulmonary arterial hypertension receive counseling about high rates of maternal morbidity and mortality; if pregnancy is pursued, the patient should be referred to a center with expertise in this condition to guide management during pregnancy and postpartum (GRADE 1C); (2) we recommend considering referral to a genetics provider with expertise in heritable cardiac disease for people with peripartum cardiomyopathy (PPCM), particularly when the index of suspicion is high and no other contributing factors are identified (GRADE 1C); (3) we recommend that other causes of heart failure be ruled out before making a diagnosis of PPCM (Best Practice); (4) for acute left ventricular heart failure during pregnancy, we recommend hydralazine or isosorbide dinitrate for afterload reduction and furosemide for diuresis. For acute left ventricular failure postpartum, we recommend afterload reduction with angiotensin-converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB), or angiotensin receptor/neprilysin inhibitor (ARNi) unless contraindicated (e.g., renal failure) (GRADE 1B); (5) we recommend against inotropic blockade (i.e., beta-blockers) in the setting of acute decompensated left ventricular heart failure (GRADE 1B); (6) we recommend prophylactic anticoagulation administration in hospitalized pregnant patients with acute left ventricular heart failure (GRADE 1C); (7) in patients who are pursuing pregnancy or pregnant, we recommend discontinuing spironolactone, ACEi, ARB, and ARNi and continuing beta-blockers (metoprolol, carvedilol, bisoprolol) (GRADE 1C); (8) for pregnant patients with left ventricular failure and ejection fraction < 35%, we recommend pharmacologic thromboprophylaxis during pregnancy and for six weeks postpartum (GRADE 1C); (9) for patients with chronic left ventricular failure, we recommend starting or continuing guideline-directed medical therapy when medically able, in consultation with experts in cardiology (GRADE 1C); (10) we recommend fetal echocardiography when maternal heart failure is a result of an underlying congenital cardiac defect (GRADE 1C); (11) we recommend serial growth ultrasounds in pregnancies complicated by maternal heart failure (GRADE 1C); (12) we recommend continuous fetal heart rate monitoring during anesthesia administration, labor, and delivery for pregnant patients with heart failure (GRADE 1B); (13) in the case of maternal cardiovascular changes prompting inpatient assessment or treatment, we recommend continuous or intermittent fetal heart rate monitoring, taking into consideration the gestational age and any relevant maternal or fetal factors that may impact fetal viability or the maternal clinical status (GRADE 1C); (14) we recommend planned vaginal delivery at term in patients with heart failure in the absence of hemodynamic compromise or obstetric indications for cesarean (GRADE 1C); (15) we recommend the use of neuraxial anesthesia in most patients with heart failure to provide appropriate analgesia and to limit the effects of labor on cardiac parameters (GRADE 1C); (16) we recommend considering a limited or assisted second stage for some patients after input from cardiology about each individual patient's cardiac risk (GRADE 1C); (17) we recommend that postpartum patients with heart failure undergo routine counseling regarding infant feeding. We recommend reviewing all medications for compatibility with breastfeeding and using shared decision-making in the absence of robust data (GRADE 1B).

Prosthetic valve endocarditis (PVE) caused by Corynebacterium diphtheriae is rare and may be associated with severe embolic complications and high mortality. In March 2026, a 61-year-old woman with a mechanical mitral valve receiving chronic acenocoumarol therapy was admitted with fever, malaise, and abdominal pain. Thoracoabdominal computed tomography revealed multiple splenic infarctions suggestive of systemic embolization. Transthoracic echocardiography demonstrated vegetations on the prosthetic mitral valve. Blood cultures yielded C. diphtheriae, identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Whole-genome sequencing confirmed a non-toxigenic C. diphtheriae sequence type 542 lacking the tox gene. Antimicrobial susceptibility testing showed resistance to penicillin G and trimethoprim-sulfamethoxazole, with susceptibility to meropenem, erythromycin, clindamycin, tetracycline, linezolid, vancomycin and rifampicin, and susceptibility with increased exposure to cefotaxime and ciprofloxacin. Cerebral computed tomography angiography demonstrated complete occlusion of the right internal carotid artery without initial parenchymal lesions. Intravenous vancomycin and bisoprolol were initiated. Acenocoumarol was initially continued and subsequently switched to intravenous unfractionated heparin. On hospital day 3, the patient developed sudden neurological deterioration with coma, hemodynamic collapse, and respiratory failure. Brain imaging revealed massive intracerebral hemorrhage with intraventricular extension and cerebral herniation. Despite intensive supportive management, the patient died. This case highlights the severe invasive potential of non-toxigenic C. diphtheriae in PVE and the risk of devastating thromboembolic and hemorrhagic neurological complications. It also emphasizes the necessity of rapid microbiological identification, integration of genomic data, and multidisciplinary management, particularly regarding anticoagulation strategies in patients with mechanical prosthetic valves.

Enantiomeric separation is essential in pharmaceutical analysis because enantiomers can differ markedly in pharmacological activity, metabolism, and safety. HPLC using chiral mobile-phase additives (CMPAs), particularly cyclodextrin-based selectors, provides a flexible and cost-effective alternative to dedicated chiral stationary phases. However, conventional cyclodextrin CMPA systems are often limited by insufficient stereodiscrimination under aqueous-organic mobile-phase conditions, where solvation and weak noncovalent interactions can restrict chiral recognition. This study explores the potential of deep eutectic solvents (DESs) as auxiliary mobile-phase modifiers for enhancing enantioseparation in β-cyclodextrin polymer-based HPLC chiral mobile phase analysis.

Background/Objectives: Diabetes mellitus type 2 (T2DM) is often associated with hypertension, necessitating treatment with combinations of medications that address both glycemic control and blood pressure. Whether commonly co-prescribed antihypertensives modify the glycemic efficacy of a sulfonylurea remains insufficiently characterized in controlled preclinical models. Methods: One hundred adult male Wistar rats were allocated to ten parallel groups (n = 10): healthy and diabetic untreated controls; glimepiride, bisoprolol or amlodipine monotherapy (in healthy and diabetic animals); and the diabetic combinations glimepiride+bisoprolol and glimepiride+amlodipine. T2DM was induced with a high-fat diet plus low-dose streptozotocin (35 mg/kg, i.p.) and confirmed by fasting blood glucose ≥ 200 mg/dL. Glycated hemoglobin (HbA1c) was measured weekly for 11 weeks. Non-parametric inference (Kruskal-Wallis, Dunn's with Bonferroni correction, Mann-Whitney U, Wilcoxon signed-rank) was complemented by Random Forest regression and PCA/K-means clustering. Results: Week-11 HbA1c differed markedly across groups (Kruskal-Wallis H = 94.3, p < 0.001). Glimepiride + bisoprolol achieved near-normal control (4.37% ± 0.15), statistically indistinguishable from healthy groups (p ≥ 0.33), and was the only diabetic regimen with a declining trajectory (-0.66 percentage points; Wilcoxon p = 0.004). Adding either antihypertensive to glimepiride did not worsen glycemic control. Amlodipine monotherapy did not attenuate hyperglycemia (8.47% ± 0.20), approaching that of untreated diabetic controls (9.31% ± 0.18), consistent with the absence of intrinsic glucose-lowering activity. All agents showed pronounced disease-state dependence (healthy-diabetic divergence 2.33-3.13 points). Random Forest prediction was accurate (R[2] = 0.985), and unsupervised clustering separated effective from ineffective regimens, corroborating the statistical findings. Conclusions: In this model, bisoprolol co-administration enhanced and amlodipine co-administration preserved glimepiride-mediated glycemic control. Glimepiride+bisoprolol emerged as the most effective regimen, supporting cardioselective β-blockade as a metabolically favorable antihypertensive partner for sulfonylurea therapy and warranting clinical confirmation. More broadly, these results provide a preclinical, evidence-based rationale for selecting metabolically favorable antihypertensives in patients with coexisting T2DM and hypertension, with the potential to improve glycemic outcomes and reduce the risk of adverse drug-disease interactions during combination therapy.

Cardiovascular diseases, such as hypertension, coronary artery diseases (CAD), arrhythmias, and chronic heart failure (CHF), often require treatment with beta-blockers. These conditions frequently coexist with chronic obstructive pulmonary disease (COPD), which can complicate therapeutic decisions. Indeed, patients with moderate-to-severe COPD are frequently not given these agents out of concern for possible bronchoconstriction arising from blockade of β2-adrenoceptors in the airways. Observational studies, and meta-analyses support the cardiovascular benefits of β-blockade in people with COPD and cardiovascular diseases. Recent trials evaluating cardioselective β-blockade suggest that cardioselective beta-blockers such as bisoprolol, metoprolol and nebivolol are safe and likely beneficial in those patients that would benefit from their intake due to presence of cardiac comorbid diseases. The aim of this systematic review is to summarise the recent trials and indications for use of cardioselective β-blockers in patients with COPD.

Hypertension is a leading chronic disease globally, with rising prevalence in China. A considerable number of hypertension patients struggle to achieve target blood pressure levels with monotherapy alone. The bisoprolol/amlodipine FDC shows promise for blood pressure control and adherence, whereas clinical evidence for Chinese patients is limited. This prospective study evaluated efficacy and safety in patients inadequately controlled by free combination of bisoprolol/metoprolol and amlodipine. In a prospective trial spanning 12 weeks across multiple centers, 78 patients were enrolled who failed 4-week free combinations (e.g., bisoprolol 2.5 mg/day or metoprolol formulations + amlodipine/levamlodipine). Inclusion required office systolic blood pressure (SBP) ≥140 mmHg and/or office diastolic blood pressure (DBP) ≥90 mmHg, with resting heart rate (RHR) ≥70 beats per minute (bpm). Assessments included office BP (OBP) at 4th, 8th, 12th weeks; home BP (HBP) at 0, 1st, 5th, 9th weeks; ambulatory BP at 0, 11 weeks; and time in target range (TTR) at 12 weeks. Patients averaged 49±12.4 years, 73.1% male. After 1 week, home SBP decreased by 6.6 mmHg, DBP by 4.2 mmHg, RHR by 5.5 bpm (all p < 0.0001). OBP significantly reduced at 4 and 8 weeks. By 12 weeks, office SBP dropped by 13.9 mmHg, DBP by 11.2 mmHg, and RHR by 11.3 bpm (all p < 0.0001). The mean Clinic TTR significantly increased by 47.9 percentage points (from 31.3% to 79.2%, p < 0.0001), with the proportion of patients achieving Clinic TTR >70% rising from 19.2% to 66.7% (p < 0.0001). At 11 weeks, ambulatory SBP and HR fell substantially (p < 0.001), and Ambulatory TTR also significantly improved across 24-hour, daytime, and nighttime periods. Bisoprolol/amlodipine FDC is safe and effective for Chinese patients with hypertension not adequately controlled by free combinations of bisoprolol/metoprolol and amlodipine.