Comparative Efficacy and Safety of Amlodipine and Losartan Potassium in Essential Hypertension in a Tertiary Hospital of Bangladesh.

Hypertension is a common disorder of major clinical, public health and economic importance. It affects men and women of all ages, and the prevalence is increasing in most countries. Maintenance of blood pressure below 140/90 mm of Hg is recommended by most of the guideline available around the world. Various classes of drugs are being used in the treatment of hypertension. Losartan potassium and amlodipine are two different antihypertensive agents belonging to two different groups used commonly around the world in treating essential hypertension. Losartan potassium is non-peptide Angiotensin-II receptor antagonist. Amlodipine which is the third generation dihydropyridine group of calcium channel blocker. The aim of the study was to compare the efficacy and safety of amlodipine and losartan for the treatment of essential hypertensive patients (18-75 years). A non-randomized comparative observational study was conducted in the Department of Pharmacology and Therapeutics in collaboration with Department of Medicine, Sylhet, MAG Osmani Medical College, Sylhet, Bangladesh from July 2021 to June 2022. In this study non-randomization was in two groups. Group A received amlodipine 5mg daily at morning and Group B received losartan potassium 50mg daily at night. The study parameters were systolic blood pressure (SBP), diastolic blood pressure (DBP), ankle oedema, serum K+ level. The result of treatment outcome was compared between two groups. After treatment the reduction of SBP was 5.19±2.93mm of Hg versus 3.27±1.34mm of Hg (p<0.001); reduction of DBP was 1.7±0.70 mm of Hg versus 0.68 mm of Hg (p<0.001) and serum K+ level 4.22±0.27mmol/L versus 4.21±0.16mmol/L (p<0.719) in amlodipine and losartan group respectively. Amlodipine is more effective than losartan potassium in respect to treatment of essential hypertension. Regarding adverse events losartan potassium causes angioedema, hyperkalemia, headache, dizziness etc. The study concluded that amlodipine is superior to losartan potassium in treating essential hypertension.

Acute quadruple extremity compartment syndrome due to angio-oedema after polypharmacy overdose including olmesartan medoxomil, telmisartan and vildagliptin.

This case report describes a rare manifestation of acute compartment syndrome (ACS) involving all four extremities, precipitated by angio-oedema in a middle-aged woman who consumed an overdose of multiple medications: nifedipine, azelnidipine, amlodipine besylate, olmesartan medoxomil, telmisartan, esaxerenone and vildagliptin. She presented with haemodynamic instability, necessitating intubation. Despite stabilising haemodynamic parameters within 24 hours, she manifested escalating extremity oedema. At 52 hours after ingestion, mottled skin was observed, along with necrotic alterations in the swollen hands and compartment pressures exceeding 30 mm Hg in all extremities. ACS was diagnosed, leading to fasciotomies. The aetiology is postulated to be drug-induced angio-oedema, possibly intensified by the concurrent overdose of olmesartan medoxomil, telmisartan and vildagliptin, each of which has a risk of angio-oedema even at standard dosages. This scenario is a very rare case caused by drug-induced angio-oedema, which underscores the importance of vigilant monitoring to detect ACS in patients with progressing limb oedema.

Amlodipine inhibits Synaptotagmin-4's oncogenic activity on gastric cancer proliferation by targeting calcium signaling.

BACKGROUND: Gastric cancer (GC) remains a leading cause of cancer mortality globally. Synaptotagmin-4 (SYT4), a calcium-sensing synaptic vesicle protein, has been implicated in the oncogenesis of diverse malignancies. PURPOSE: This study delineates the role of SYT4 in modulating clinical outcomes and biological behaviors in GC. METHODS: We evaluated SYT4 expression in GC specimens using bioinformatics analyses and immunohistochemistry. Functional assays included CCK8 proliferation tests, apoptosis assays via flow cytometry, confocal calcium imaging, and xenograft models. Western blotting elucidated MAPK pathway involvement. Additionally, we investigated the impact of the calcium channel blocker amlodipine on cellular dynamics and MAPK pathway activity. RESULTS: SYT4 was higher in GC tissues, and the elevated SYT4 was significantly correlated with adverse prognosis. Both univariate and multivariate analyses confirmed SYT4 as an independent prognostic indicator for GC. Functionally, SYT4 promoted tumorigenesis by fostering cellular proliferation, inhibiting apoptosis, and enhancing intracellular Ca2+ influx, predominantly via MAPK pathway activation. Amlodipine pre-treatment attenuated SYT4-driven cell growth and potentiated apoptosis, corroborated by in vivo xenograft assessments. These effects were attributed to MAPK pathway suppression by amlodipine. CONCLUSION: SYT4 emerges as a potential prognostic biomarker and a pro-oncogenic mediator in GC through a Ca2+-dependent MAPK mechanism. Amlodipine demonstrates significant antitumor effects against SYT4-driven GC, positing its therapeutic promise. This study underscores the imperative of targeting calcium signaling in GC treatment strategies.

Design of Experimental Approach for Development of Rapid High Performance Liquid Chromatographic Process for Simultaneous Estimation of Metoprolol, Telmisartan, and Amlodipine from Formulation: Greenness and Whiteness Evaluation.

The design of an experimental approach, the Box-Behnken design, was implemented to optimize the chromatographic condition to develop a rapid HPLC procedure for quantification of a ternary mixture of metoprolol (MET), telmisartan (TEL), and amlodipine (AML) from the formulation. The perturbation plots, contour, and 3D response surface pictures were developed to study the impact of each variable on the analytes' retention time and the probable interaction between the parameters with fewer chromatographic runs. The optimized HPLC method separated the three analytes within 5 min with excellent selectivity and peak shape on a Zorbax C18 HPLC column using acetonitrile and phosphate buffer (20 mM, pH 5.8) with isocratic elution at a 1.1 mL/min flowrate. A wavelength 230 nm was utilized to monitor the elute. The validation of proposed method demonstrated a wide linearity range of 10-200 µg/mL for MET and TEL and 5-50 µg/mL for AML along with an excellent correlation coefficient. The correctness of the HPLC approach was further confirmed by excellent recovery of the added amount of analytes utilizing the standard addition technique. The recommended HPLC approach was employed safely for quality assurance of the formulation, because the evaluation of the method's greenness and whiteness confirmed the environmentally friendly nature of the approach.

Effect of Concomitant Drugs on Sodium Zirconium Cyclosilicate Hydrate in Artificial Intestinal Juice.

To explore drug interactions involving sodium zirconium cyclosilicate hydrate (SZC) and concomitant drugs like calcium antagonists (amlodipine and nifedipine) and ß-blockers (carvedilol and bisoprolol), we investigate how these concomitant drugs influenced the administration of SZC in an artificial intestinal juice. Initially, we assessed the potassium ion adsorption capacity, ranking it as follows: calcium polystyrene sulfonate (CPS, 54.9 mg/g) < sodium polystyrene sulfonate (SPS, 62.1 mg/g) < SZC (90.8 mg/g). However, the adsorption equilibrium was achieved in the order of CPS ≒ SPS (within 1 min) < SZC (within 1 h). Subsequently, we determined the residual percentages of amlodipine, nifedipine, carvedilol, and bisoprolol, finding them to be 79.0-91.9% for SZC, 0.38-38.4% for SPS, and 0.57-29.0% for CPS. These results suggest the efficacy of SZC in managing hyperkalemia alongside concomitant drugs in an artificial intestinal juice, with particular emphasis on amlodipine (calcium antagonist) and carvedilol (ß-blocker). Additionally, we identified the presence of carbon, nitrogen, and oxygen components from both drugs on the SZC surface following interaction. We also evaluated how amlodipine, nifedipine, carvedilol, and bisoprolol affected the administration of SZC in the presence of potassium ions. Our results indicate that potassium ions and concomitant drugs did not interfere with each other in the artificial intestinal juice. These results offer valuable insights into the administration of SZC in conjunction with concomitant drugs. Lastly, the presented data shows qualitative results in this study.

India Hypertension Control Initiative: Blood Pressure Control Using Drug and Dose-Specific Standard Treatment Protocol at Scale in Punjab and Maharashtra, India, 2022.

Background: Hypertension treatment coverage is low in India. A stepwise simple treatment protocol is one of the strategies to improve hypertension treatment in primary care. We estimated the effectiveness of various protocol steps to achieve blood pressure (BP) control in public sector health facilities in Punjab and Maharashtra, India, where the India Hypertension Control Initiative (IHCI) was implemented. Methods: We analyzed the records of people enrolled for hypertension treatment and follow-up under IHCI between January 2018 and December 2021 in public sector primary and secondary care facilities across 23 districts from two states. Each state followed a different treatment protocol. We calculated the proportion with controlled BP at each step of the protocol. We also estimated the mean decline in BP pre- and post-treatment. Results: Of 281,209 patients initiated on amlodipine 5 mg, 159,292 continued on protocol drugs and came for a follow-up visit during the first quarter of 2022. Of 33,450 individuals who came for the follow-up in Punjab and 125,842 in Maharashtra, 70% and 76% had controlled BP, respectively, at the first step with amlodipine 5 mg. In Punjab, at the second step with amlodipine 10 mg, the cumulative BP control increased to 75%. A similar 5% (76%-81%) increase was seen in the second step after adding telmisartan 40 mg in Maharashtra. Overall, the mean (SD) systolic blood pressure (SBP) decreased by 16 mmHg from 148 (15) mmHg at the baseline in Punjab. In Maharashtra, the decline in the mean (SD) SBP was about 15 mmHg from the 144 (18) mmHg baseline. Conclusion: Simple drug- and dose-specific protocols helped achieve a high control rate among patients retained in care under program conditions. We recommend treatment protocols starting with a single low-cost drug and escalating with the same or another antihypertensive drug depending on the cost and availability.

Hemoadsorption Therapy for Calcium Channel Blocker Overdose: A Case Report.

BACKGROUND: Modern resin hemoadsorption/hemoperfusion for calcium channel blocker overdose is yet to be reported. The characteristics of calcium channel blockers make them unamenable to removal by hemodiafiltration or charcoal hemoperfusion; however, elimination, using styrene bead adsorption in an ex vivo model, has been demonstrated. Its clinical use is described. CASE REPORT: A man in his 20s was admitted with shock into the Intensive Care Unit (ICU) after an overdose of amlodipine and risperidone. Resuscitation and supportive care were administered, but hypotension did not resolve despite the administration of intravenous fluids, infusions of calcium, adrenaline, and hyperinsulinemic-euglycemic therapy. Methylene blue was then administered to maintain the mean arterial pressures. However, the hemodynamic effect did not allow the weaning of the adrenaline. Drug clearance using hemoadsorption/hemoperfusion was attempted using a styrene resin filter (Jafron HA230; Jafron Biomedical Co., Ltd., Guangdong, China). During the two hemoperfusion sessions (6 h duration each, and 18 h apart) the patient had successfully weaned off all supportive measures, with lactate levels returning to normal and was later discharged home. At the end of each session, significant amlodipine concentrations were detected in blood aspirated from both filters, suggesting enhanced clearance. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Our case illustrates a temporal relationship between resin hemoperfusion therapy, resolution of hemodynamic instability, and shock without proving causation. Significant amlodipine elimination was suggested by high concentrations found in blood from the filter. At the same time, shock resolution after initiation of hemoperfusion occurred in less than one elimination half-life of amlodipine.

S-amlodipine induces liver inflammation and dysfunction through the alteration of intestinal microbiome in a rat model.

S-amlodipine, a commonly prescribed antihypertensive agent, is widely used in clinical settings to treat hypertension. However, the potential adverse effects of long-term S-amlodipine treatment on the liver remain uncertain, given the cautionary recommendations from clinicians regarding its administration in individuals with impaired liver function. To address this, we conducted a study using an eight-week-old male rat model and administered a daily dose of 0.6 ~ 5 mg/kg of S-amlodipine for 7 weeks. Our findings demonstrated that 1.2 ~ 5 mg/kg of S-amlodipine treatment induced liver inflammation and associated dysfunction in rats, further in vitro experiments revealed that the observed liver inflammation and dysfunction were not attributable to direct effects of S-amlodipine on the liver. Metagenome sequencing analysis revealed that S-amlodipine treatment led to alterations in the gut microbiome of rats, with the bloom of E. coli (4.5 ~ 6.6-fold increase) and a decrease in A. muciniphila (1,613.4 ~ 2,000-fold decrease) and B. uniformis (20.6 ~ 202.7-fold decrease), subsequently causing an increase in the gut bacterial lipopolysaccharide (LPS) content (1.4 ~ 1.5-fold increase in feces). S-amlodipine treatment also induced damage to the intestinal barrier and increased intestinal permeability, as confirmed by elevated levels of fecal albumin; furthermore, the flux of gut bacterial LPS into the bloodstream through the portal vein resulted in an increase in serum LPS content (3.3 ~ 4-fold increase). LPS induces liver inflammation and subsequent dysfunction in rats by activating the TLR4 pathway. This study is the first to show that S-amlodipine induces liver inflammation and dysfunction by perturbing the rat gut microbiome. These results indicate the adverse effects of S-amlodipine on the liver and provide a rich understanding of the safety of long-term S-amlodipine administration.

Personalized Antihypertensive Treatment Optimization With Smartphone-Enabled Remote Precision Dosing of Amlodipine During the COVID-19 Pandemic (PERSONAL-CovidBP Trial).

BACKGROUND: The objective of the PERSONAL-CovidBP (Personalised Electronic Record Supported Optimisation When Alone for Patients With Hypertension: Pilot Study for Remote Medical Management of Hypertension During the COVID-19 Pandemic) trial was to assess the efficacy and safety of smartphone-enabled remote precision dosing of amlodipine to control blood pressure (BP) in participants with primary hypertension during the COVID-19 pandemic. METHODS AND RESULTS: This was an open-label, remote, dose titration trial using daily home self-monitoring of BP, drug dose, and side effects with linked smartphone app and telemonitoring. Participants aged ≥18 years with uncontrolled hypertension (5-7 day baseline mean ≥135 mm Hg systolic BP or ≥85 mm Hg diastolic BP) received personalized amlodipine dose titration using novel (1, 2, 3, 4, 6, 7, 8, 9 mg) and standard (5 and 10 mg) doses daily over 14 weeks. The primary outcome of the trial was mean change in systolic BP from baseline to end of treatment. A total of 205 participants were enrolled and mean BP fell from 142/87 (systolic BP/diastolic BP) to 131/81 mm Hg (a reduction of 11 (95% CI, 10-12)/7 (95% CI, 6-7) mm Hg, P<0.001). The majority of participants achieved BP control on novel doses (84%); of those participants, 35% were controlled by 1 mg daily. The majority (88%) controlled on novel doses had no peripheral edema. Adherence to BP recording and reported adherence to medication was 84% and 94%, respectively. Patient retention was 96% (196/205). Treatment was well tolerated with no withdrawals from adverse events. CONCLUSIONS: Personalized dose titration with amlodipine was safe, well tolerated, and efficacious in treating primary hypertension. The majority of participants achieved BP control on novel doses, and with personalization of dose there were no trial discontinuations due to drug intolerance. App-assisted remote clinician dose titration may better balance BP control and adverse effects and help optimize long-term care. REGISTRATION: URL: clinicaltrials.gov. Identifier: NCT04559074.

Effect of amlodipine on the circulating renin-angiotensin-aldosterone system in healthy cats.

BACKGROUND: Systemic hypertension (SH) is a common cardiovascular disease in older cats that is treated primarily with the calcium channel blocker amlodipine besylate (AML). The systemic effect of AML on the classical and alterative arms of the renin-angiotensin-aldosterone system (RAAS) in cats is incompletely characterized. HYPOTHESIS/OBJECTIVES: To determine the effect of AML compared to placebo on circulating RAAS biomarkers in healthy cats using RAAS fingerprinting. ANIMALS: Twenty healthy client-owned cats. METHODS: Cats were administered amlodipine besylate (0.625 mg in toto) or placebo by mouth once daily for 14 days in a crossover design with a 4-week washout period. Plasma AML concentrations and RAAS biomarker concentrations were measured at multiple timepoints after the final dose in each treatment period. Time-weighted averages for RAAS biomarkers over 24 hours after dosing were compared between treatment groups using Wilcoxon rank-sum testing. RESULTS: Compared to placebo, AML treatment was associated with increases in markers of plasma renin concentration (median 44% increase; interquartile range [IQR] 19%-86%; P = .009), angiotensin I (59% increase; IQR 27-101%; P = .006), angiotensin II (56% increase; IQR 5-70%; P = .023), angiotensin IV (42% increase; -19% to 89%; P = .013); and angiotensin 1-7 (38% increase; IQR 9-118%; P = .015). CONCLUSIONS AND CLINICAL IMPORTANCE: In healthy cats, administration of AML resulted in nonspecific activation of both classical and alternative RAAS pathways.

Safety and efficacy of candesartan versus valsartan combined with amlodipine on peripheral and central blood pressure.

INTRODUCTION: "Amlodipine/valsartan" or "amlodipine/candesartan" combinations represent two effective antihypertensive agents with complementary mechanisms of action. Nevertheless, a study has yet to be done to evaluate the effect of amlodipine/candesartan on central blood pressure and compare it with amlodipine/valsartan combination. To see how "amlodipine plus candesartan combination" reduces peripheral and central blood pressure compared to the most studied combination, "amlodipine plus valsartan". MATERIAL AND METHODS: Eighty-six patients were randomized in an open-label, prospective study by 1:1 ratio to two groups. Group I (n=42) received the amlodipine and valsartan combination, and group II (n=44) received the amlodipine and candesartan combination. Peripheral and central blood pressure (CBP) was measured at baseline, at 6 and 12 weeks of follow-up. DISCUSSION: Both treatment groups reduced peripheral systolic, diastolic, and mean blood pressure. There was no significant difference between and within both groups. The amlodipine/candesartan combination showed more reduction in peripheral systolic blood pressure (PSBP) after 12 weeks of treatment (p=<0.001). Both groups decreased CBP without significant differences between groups. The amlodipine/candesartan combination showed additional efficacy in decreasing CSBP after 12 weeks (p=<0.001). The two treatment groups did not exert significant efficacy in lowering heart rate (HR) and augmentation index% (AIx%). CONCLUSION: To conclude, the amlodipine 10mg/candesartan 16mg combination was non-inferior to the amlodipine 10mg/valsartan 160mg combination in terms of reducing peripheral and CBP over time.

Effects of allisartan-isoproxil-based combination antihypertensive regimen in hypertensive patients with microalbuminuria or hyperuricemia.

Microalbuminuria and hyperuricemia management are crucial for the integrated management of hypertensive patients. This retrospective post hoc analysis aims to evaluate the optimal allisartan-isoproxil-based combination regimen for hypertensive patients with microalbuminuria or hyperuricemia. A total of 460 hypertensive patients with microalbuminuria and 486 hypertensive patients with hyperuricemia were included in this study. All patients were initially treated with allisartan-isoproxil for 4 weeks. Thereafter, patients with blood pressure (BP) < 140/90 mmHg continued the monotherapy for 8 weeks; patients with BP ≥140/90 mmHg were randomly assigned in a 1:1 ratio to receive allisartan-isoproxil + amlodipine (Group A + C) or allisartan-isoproxil + indapamide (Group A + D) for 8 weeks. The changes of BP, urinary albumin and serum uric acid (UA) were measured. In patients with microalbuminuria, the urinary albumin/creatinine ratio (UACR) significantly decreased by 10.4 mg/g in Group A + C (vs. baseline p = .0035) and 24.2 mg/g in Group A + D (vs baseline p < .0001), intergroup p = NS. In patients with hyperuricemia, serum UA level decreased by 44.5 µmol/L in Group A + C (vs. baseline p = .0003), but increased by 27.2 µmol/L in Group A + D (vs. baseline p = .0167), intergroup p < .0001. The results suggest that for hypertensive patients with microalbuminuria, angiotensin receptor blocker (ARB) + calcium channel blocker (CCB) or ARB+ diuretic both are good choices based on their improvement of microalbuminuria and BP. But for patients with hyperuricemia, ARB + diuretic may further increase the level of UA.

Amlodipine inhibits the proliferation and migration of esophageal carcinoma cells through the induction of endoplasmic reticulum stress.

BACKGROUND: L-type calcium channels are the only protein channels sensitive to calcium channel blockers, and are expressed in various cancer types. The Cancer Genome Atlas database shows that the mRNA levels of multiple L-type calcium channel subunits in esophageal squamous cell carcinoma tumor tissue are significantly higher than those in normal esophageal epithelial tissue. Therefore, we hypothesized that amlodipine, a long-acting dihydropyridine L-type calcium channel blocker, may inhibit the occurrence and development of esophageal cancer (EC). AIM: To investigate the inhibitory effects of amlodipine on EC through endoplasmic reticulum (ER) stress. METHODS: Cav1.3 protein expression levels in 50 pairs of EC tissues and corresponding paracancerous tissues were examined. Subsequently, the inhibitory effects of amlodipine on proliferation and migration of EC cells in vitro were detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and Transwell assays. In vivo experiments were performed using murine xenograft model. To elucidate the underlying mechanisms, in vitro cell studies were performed to confirm that ER stress plays a role in inhibition proliferation and migration of EC cells treated with amlodipine. RESULTS: The expression level of Cav1.3 in esophageal carcinoma was 1.6 times higher than that in paracancerous tissues. Amlodipine treatment decreased the viability of esophageal carcinoma cells in a dose- and time-dependent manner. In vivo animal experiments also clearly indicated that amlodipine inhibited the growth of EC tumors in mice. Additionally, amlodipine reduces the migration of tumor cells by inhibiting epithelial-mesenchymal transition (EMT). Mechanistic studies have demonstrated that amlodipine induces ER stress-mediated apoptosis and suppresses EMT. Moreover, amlodipine-induced autophagy was characterized by an increase in autophagy lysosomes and the accumulation of light chain 3B protein. The combination of amlodipine with the ER stress inhibitor 4-phenylbutyric acid further confirmed the role of the ER stress response in amlodipine-induced apoptosis, EMT, and autophagy. Furthermore, blocking autophagy increases the ratio of apoptosis and migration. CONCLUSION: Collectively, we demonstrate for the first time that amlodipine promotes apoptosis, induces autophagy, and inhibits migration through ER stress, thereby exerting anti-tumor effects in EC.

Revisiting column selectivity choices in ultra-high performance liquid chromatography-Using multidimensional analytical Design Spaces to identify column equivalency.

Current guides and column selection system (CSS) platforms can provide some helpful insights with regard to the selection of alternative phases. Their practical reliability however, can also turn out to be questionable, especially considering the lack of detailed specifics, such as a clear definition of points of equivalence-appropriate running conditions under which the given analytical mixture can be satisfactorily resolved on various stationary phases. In this context, the use of multivariate modeling tools can be highly beneficial. These tools, when applied systematically, are ideal for uniquely characterizing complex LC-separation systems, a fact supported by numerous peer-reviewed papers. Revisiting our earlier work [1] and the applied systematic workflow [2], we used a Design Space modeling software (DryLab), with the main focus on building and comparing 3-dimensional separation models of amlodipine and its related impurities to identify shared method conditions under which columns are conveniently interchangeable. Our study comprised 5, C18-modified ultra-high performance liquid chromatography (UHPLC) columns in total, in some cases with surprising results. We identified several equivalences between the Design Spaces (DSs) of markedly different columns. Conversely, there were cases where, despite the predicted similarities in column data, the modeled DSs demonstrated clear differences between the selected stationary phases.

Seasonal variation in ambulatory blood pressure control in patients on clinic blood pressure-guided antihypertensive treatment.

BACKGROUND: We investigated seasonal variation in ambulatory blood pressure control in hypertensive patients on clinic blood pressure-guided antihypertensive treatment. METHODS: The study participants were hypertensive patients enrolled in an 8-week therapeutic study. Antihypertensive treatment was initiated with long-acting dihydropyridine calcium channel blockers amlodipine 5 mg/day or the gastrointestinal therapeutic system (GITS) formulation of nifedipine 30 mg/day, with the possible up-titration to amlodipine 10 mg/day or nifedipine-GITS 60 mg/day at 4 weeks of follow-up. RESULTS: The proportion of up-titration to higher dosages of antihypertensive drugs at 4 weeks of follow-up was higher in patients who commenced treatment in autumn/winter ( n  = 302) than those who commenced treatment in spring/summer ( n  = 199, 24.5 vs. 12.0%, P  < 0.001). The control rate of clinic blood pressure, however, was lower in autumn/winter than in spring/summer at 4 (56.7 vs. 70.7%, P  = 0.003) and 8 weeks of follow-up (52.5 vs. 74.9%, P  < 0.001). At 8 weeks, patients who commenced treatment in autumn/winter, compared with those who commenced treatment in spring/summer, had a significantly ( P ≤0.03) smaller daytime (mean between-season difference -3.2/-2.8 mmHg) but greater nighttime SBP/DBP reduction (3.6/1.6 mmHg). Accordingly, at 8 weeks, the prevalence of nondippers was significantly ( P  < 0.001) higher in spring/summer than in autumn/winter for both SBP (54.8 vs. 30.0%) and DBP (53.4 vs. 28.8%). CONCLUSION: Clinic blood pressure-guided antihypertensive treatment requires a higher dosage of medication in cold than warm seasons, which may have led to over- and under-treatment of nighttime blood pressure, respectively.

Initial treatment with a single capsule containing half-dose quadruple therapy versus standard-dose dual therapy in hypertensive patients (QUADUAL): statistical analysis plan for a randomized, blinded, crossover trial.

BACKGROUND: Combined antihypertensive therapy has obvious advantages over single drug therapy. Hypertension guidelines fully affirm the efficacy of dual combination in initial antihypertensive therapy. Recent studies have also pointed out that the quadruple combination of very low-dose antihypertensive drugs is superior to single drugs. However, whether low-dose quadruple therapy is better than dual combination is unknown. METHODS/DESIGN: A randomized double-blind crossover clinical trial will be conducted to compare the efficacy and safety of low-dose quadruple antihypertensives (irbesartan 75 mg + metoprolol 23.75 mg + amlodipine 2.5 mg + indapamide 1.25 mg) with standard-dose dual antihypertensives (irbesartan 150 mg + amlodipine 5 mg) in the initial treatment of patients with mild to moderate hypertension (140-179/90-109 mmHg). Ninety patients are required and will be recruited and randomly assigned in a 1:1 ratio to two crossover groups. Two groups will receive a different combination therapy for 4 weeks, then switch to the other combination therapy for 4 weeks, with a 2-week wash-out. Antihypertensive effects and related adverse effects of the two antihypertensive combination treatments will be compared. The primary outcome, i.e., mean 24-h systolic blood pressure in ambulatory blood pressure monitoring, will be assessed via linear mixed-effects model. DISCUSSION: This statistical analysis plan will be confirmed prior to blind review and data lock before un-blinding and is sought to increase the validity of the QUADUAL trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05377203. Registered May 11, 2022, https://clinicaltrials.gov/study/NCT05377203 .

Application of a white and green spectrofluorimetric approach for facile quantification of amlodipine, a hypotensive drug, in batch materials, dosage forms, and biological fluids; content homogeneity testing.

The suggested study adheres to a particular protocol to ensure that the process is environmentally friendly and sustainable. It is worth mentioning that several tools have been adopted as prospective measures of the method greenness. Fortunately, the established analytical method is identified as white by the white analytical chemistry (WAC) concept, which uses the red/ green/blue color scheme (RGB 12 tool) to combine ecological and functional factors for the first time in studying of the cited drug. Amlodipine (AMD), a cardiovascular treating agent, belongs to the dihydropyridine class of oral calcium channel-blocking agents. This article presents a novel, simple, green, one-pot-processed, fast, and ultrasensitive fluorimetric approach for monitoring and assessment of AMD using molecular-size-dependent fluorescence augmentation of the light scattering-driven signal of eosin, a biological stain at a wavelength of 415 nm. This enhancement was directly proportional to the size of the produced complex. The linearity range was from 30 to 900 ng mL-1 , with corresponding sensitivity limits (detection and quantitation levels) of 9.2 and 28 ng mL-1 , respectively. The planned approach was also successfully used to track AMD content in bulk, dosage forms, and bio-fluids (human plasma and urine). The developed method's eco-friendliness was established by different eco-rating metric tools.

Comparison of two single-pill dual combination antihypertensive therapies in Chinese patients: a randomized, controlled trial.

BACKGROUND: Current hypertension guidelines recommend combination of an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker with a calcium-channel blocker or thiazide diuretic as initial antihypertensive therapy in patients with monotherapy uncontrolled hypertension. However, to what extent these two different combinations are comparable in blood pressure (BP)-lowering efficacy and safety remains under investigation, especially in the Chinese population. We investigated the BP-lowering efficacy and safety of the amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies in Chinese patients. METHODS: In a multi-center, randomized, actively controlled, parallel-group trial, we enrolled patients with stage 1 or 2 hypertension from July 2018 to June 2021 in 20 hospitals and community health centers across China. Of the 894 screened patients, 560 eligible patients were randomly assigned to amlodipine/benazepril 5/10 mg (n = 282) or benazepril/hydrochlorothiazide 10/12.5 mg (n = 278), with 213 and 212 patients, respectively, who completed the study and had a valid repeat ambulatory BP recording during follow-up and were included in the efficacy analysis. The primary outcome was the change from baseline to 24 weeks of treatment in 24-h ambulatory systolic BP. Adverse events including symptoms and clinically significant changes in physical examinations and laboratory findings were recorded for safety analysis. RESULTS: In the efficacy analysis (n = 425), the primary outcome, 24-h ambulatory systolic BP reduction, was - 13.8 ± 1.2 mmHg in the amlodipine/benazepril group and - 12.3 ± 1.2 mmHg in the benazepril/hydrochlorothiazide group, with a between-group difference of - 1.51 (p = 0.36) mmHg. The between-group differences for major secondary outcomes were - 1.47 (p = 0.18) in 24-h diastolic BP, - 2.86 (p = 0.13) and - 2.74 (p = 0.03) in daytime systolic and diastolic BP, and - 0.45 (p = 0.82) and - 0.93 (p = 0.44) in nighttime systolic and diastolic BP. In the safety analysis (n = 560), the incidence rate of dry cough was significantly lower in the amlodipine/benazepril group than in the benazepril/hydrochlorothiazide group (5.3% vs 10.1%, p = 0.04). CONCLUSIONS: The amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies were comparable in ambulatory systolic BP lowering. The former combination, compared with the latter, had a greater BP-lowering effect in the daytime and a lower incidence rate of dry cough. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03682692. Registered on 18 September 2018.