Safety and efficacy of candesartan versus valsartan combined with amlodipine on peripheral and central blood pressure / Seguridad y eficacia de candesartán frente a valsartán combinado con amlodipino sobre la presión arterial periférica y central

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.(AU)

Introducción: «Las combinaciones de amlodipino/valsartán» o «amlodipino/candesartán» representan 2 agentes antihipertensivos efectivos con mecanismos de acción complementarios. Sin embargo, aún no se ha realizado un estudio para evaluar el efecto del amlodipino/candesartán en la presión arterial central y compararlo con la combinación amlodipino/valsartán. En este estudio, se comparó la reducción de la presión arterial periférica y central entre estas 2 combinaciones. Materiales y métodos: Ochenta y seis pacientes fueron asignados aleatoriamente a 2 grupos: el Grupo I (n=42) recibió amlodipino y valsartán, y el Grupo II (n=44) recibió amlodipino y candesartán. Se midió la presión arterial periférica y central al inicio, a las 6 y 12 semanas de seguimiento. Discusión: Ambos grupos redujeron la presión arterial periférica de manera similar, pero la combinación amlodipino/candesartán mostró una mayor reducción en la presión arterial sistólica periférica después de 12 semanas de tratamiento. Ambas combinaciones también disminuyeron la presión arterial central, pero nuevamente, la combinación amlodipino/candesartán tuvo una mayor eficacia en la reducción de la presión arterial sistólica central después de 12 semanas. No se observaron diferencias significativas en la frecuencia cardíaca ni en el índice de aumento entre los grupos. Conclusión: En conclusión, la combinación de amlodipino 10mg/candesartán 16mg demostró ser tan efectiva como la combinación de amlodipino 10mg/valsartán 160mg en la reducción tanto de la presión arterial periférica como central a lo largo del tiempo.(AU)

Efficacy and safety of amlodipine/valsartan/hydrochlorothiazide single pill combination in Egyptian patients with hypertension uncontrolled on any dual therapy: an observational study.

Objective: Hypertension is a serious health problem in Egypt, with prevalence rate of 17% as reported in 2015. Despite receiving treatment, many do not achieve blood pressure (BP) control. The current study aimed to evaluate the efficacy and tolerability of amlodipine/valsartan/hydrochlorothiazide (Aml/Val/HCTZ) single pill combination (SPC) in patients with hypertension from Egypt, who were uncontrolled on any dual therapy.Methods: In this prospective, open label, multicenter, 12-week observational, cohort study, two doses of Aml/Val/HCTZ (5/160/12.5 mg or 10/160/25 mg) SPC were used to evaluate mean change in BP after 12 weeks (primary endpoint). Safety assessments included presence and intensity of ankle edema and other adverse events (AEs).Results: Data were collected from 1080 patients who were treated according to the routine medical practice across 47 centers in Egypt. Significant reduction in systolic and diastolic BP (SBP/DBP) was observed from 165.5 ± 12.83/100.8 ± 7.03 mmHg at baseline to 129.7 ± 8.35/80.6 ± 5.25 mmHg after 12 weeks of treatment (p < .0001). Majority of patients (76.85%) reached the BP goal of <140/90 mmHg. The most commonly reported AE was ankle edema (10.92%).Conclusions: Aml/Val/HCT SPC significantly reduced BP and was well tolerated in Egyptian patients with hypertension not controlled on any previous dual therapy.

Pharmacokinetic and Safety Profiles of a Fixed-Dose Combination of Amlodipine, Valsartan, and Atorvastatin: A 3-Period Replicate Crossover Study.

The objective of study was to compare the pharmacokinetic and safety profiles of a fixed-dose combination (FDC) formulation of 5/160/20 mg amlodipine/valsartan/atorvastatin with those of separate formulations of a 5/160-mg amlodipine/valsartan tablet and a 20-mg atorvastatin tablet. This was a randomized, open-label, single-dose, 3-sequence, 3-period replicate crossover study with 42 subjects. Serial blood samples for pharmacokinetic assessment were collected up to 72 hours postdose. For establishing bioequivalence (BE) for amlodipine, valsartan, and atorvastatin, a reference-scaled average BE approach was used if applicable, as well as the conventional limit of 0.80-1.25. The 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) for the maximum plasma concentration (Cmax ) and the area under the curve to the last measurable concentration (AUCt ) between the FDC and separate formulations were within the 0.80-1.25 limit for all analytes but atorvastatin. The estimated within-subject standard deviation of the log-transformed values of the separate formulations, the reference intervention, was 0.3804 for the Cmax of atorvastatin, being set at 0.7489-1.3352 for the BE acceptance limit. For both the Cmax and AUCt for atorvastatin, the GMRs lay within 0.80-1.25, and the 90%CIs for the GMRs were within the BE acceptance limit. This 3-period replicate crossover study demonstrated the BE of the FDC formulation of amlodipine, valsartan, and atorvastatin and the separate formulations of an amlodipine/valsartan tablet and an atorvastatin tablet. A similar incidence of treatment-emergent adverse events (TEAEs) was observed in both interventions, and headache was the most common TEAE.

Chart review of patients receiving valsartan-amlodipine single-pill combination versus valsartan and amlodipine combination for blood pressure goal achievement and effects on the Hamilton anxiety rating/Hamilton depression rating scales.

This study aimed to compare the Hamilton anxiety rating/Hamilton depression rating (HAMA/HAMD) scale scores and blood pressure (BP) goal achievement associated with the use of valsartan-amlodipine single-pill combinations (SPCs) versus valsartan and amlodipine combination in adult hypertensive patients.A total of 476 hypertensive patients were randomly assigned into the SPC (valsartan-amlodipine) and control (valsartan and amlodipine combination) groups. All patients had an uncontrolled BP (160-179/100-109 mm Hg). BP goal was <140/90 mm Hg. Cox proportional hazards regression analysis was used to analyze the likelihood of HAMA/HAMD scales, SPCs, control group, and daily dosage number. Kaplan-Meier analysis was used to estimate the rates of BP goal achievement over time among the 2 groups.A total of 476 patients were included in the study, and 439 patients completed the follow-up and received the index drug therapy. There was a significant difference in BP between the 2 groups on days 28, 42, and 56. Patients who received SPCs had a significantly higher rate of BP goal achievement over time (P = .000). The average HAMD scores in the SPC and control groups were 5.54 and 5.49 and 6.06 and 6.21 on days 28 and 56, respectively. The average HAMA scores in the SPC and control groups were 7.41 and 7.13 and 7.90 and 8.01 on days 28 and 56, respectively. The means of HAMD and HAMA scores were 5.826 and 7.614, respectively. The higher the HAMA/HAMD scores, the lower was the BP goal achievement. The number of drugs taken by the patients was associated with the HAMA and HAMD scores. There was no significant difference between HAMA scores of patients taking 1 tablet daily (7.22 ±â€Š1.885) and those taking two-tablets daily (7.38 ±â€Š1.953) (P = .408). However, when these scores were compared to those of patients taking 4 tablets daily (8.08 ±â€Š2.285), a significant difference was observed (P = .000, P = .000).Hypertensive patients treated with valsartan-amlodipine SPCs were significantly more likely to achieve BP goal and have lesser HAMA/HAMD scores compared to patients treated with valsartan and amlodipine combination.

Efficacy of amlodipine besylate and Valsartan for the treatment of mild to moderate hypertension.

BACKGROUND: Clinical researchers found that Amlodipine besylate and Valsartan (ABVS) can effectively treat mild to moderate hypertension (MMH). However, no study has systematically investigated its efficacy and safety for patients with MMH. Thus, present study will systematically assess the efficacy and safety of ABVS for patients with MMH. METHODS: MEDICINE, Cochrane Library, EMBASE, Ovid, PsycINFO, Web of Science, Allied and Complementary Medicine Database, and China National Knowledge Infrastructure will be searched for literatures related to the topic from inception to the present without language limitations. All randomized controlled trials that assess the efficacy and safety of ABVS for patients with MMH will be considered for inclusion. Two researchers will independently select study, extract data, and assess risk of bias for all eligible studies. RESULTS: The primary outcome includes the change of seated diastolic blood pressure. The secondary outcomes consist of the change of seated systolic blood pressure, health-related quality of life, and the tolerability. CONCLUSIONS: The results of this study will summarize the latest evidence on ABVS for the treatment of MMH. ETHICS AND DISSEMINATION: This study does not need ethical approval, because it will not use individual data. The results of this study are expected to be published at peer-reviewed journals. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019133123.

Efficacy of a new single-pill combination of a thiazide-like diuretic and a calcium channel blocker (indapamide sustained release/amlodipine) in essential hypertension.

OBJECTIVES: The current international, 12-week, double-blind, randomized, controlled trial assessed the efficacy and safety of indapamide sustained release/amlodipine single-pill combination (SPC) in mild-to-moderate hypertensive patients. METHODS: Following a 4-week run-in period on amlodipine 5 mg, patients (SBP 150-180 mmHg and/or DBP < 110 mmHg) were randomized to indapamide 1.5 mg sustained release/amlodipine 5 mg SPC or amlodipine 5 mg/valsartan 80 mg SPC with conditional uptitration at week 6. Office blood pressure (BP) was assessed at baseline, weeks 6 and 12; ambulatory and home blood pressure monitoring (ABPM/HBPM) at baseline and week 12. RESULTS: Baseline characteristics were similar in both groups (57 years, 51% men, BP 160/92 mmHg). 233 patients were randomized to IndSR/Aml and 232 to amlodipine/valsartan, of whom 48 and 57% were uptitrated, respectively. After 12 weeks, office SBP/DBP decreased similarly with both treatments (-21/-8 vs. -20/-8 mmHg) leading to BP control in 50% and BP response in 70% of patients. Uptitration was effective (P < 0.001) with both regimens, in favour of IndSR/Aml (SBP/DBP -12/-6 vs. -7/-3 mmHg, respectively). ABPM (n = 273) and HBPM (n = 194) confirmed 24-h efficacy of both regimens. In the subgroup of patients with sustained uncontrolled hypertension assessed by ABPM (n = 216), office SBP/DBP decreased by -23/-13 vs. -18/-10 mmHg, respectively (P = 0.016/P = 0.135, post-hoc analysis). Both treatments were generally well tolerated. CONCLUSION: Both regimens produced effective BP reductions confirmed by ABPM/HBPM. Both treatments were well tolerated, in accordance with the individual agents' safety profile. TRIAL REGISTRATION NUMBER: EUDRA CT no. 2012-001690-84.

A randomized multicenter study on ambulatory blood pressure and arterial stiffness in patients treated with valsartan/amlodipine or nifedipine GITS.

In a pre-specified subgroup analysis of a 12-week randomized multicenter study, we investigated effects of valsartan/amlodipine 80/5 mg single-pill combination (n = 75) and nifedipine GITS 30 mg (n = 75) on ambulatory blood pressure (BP) and arterial stiffness assessed by brachial-ankle pulse wave velocity (PWV) in patients with uncontrolled hypertension. At week 12, the between-treatment mean differences in systolic/diastolic BP were smaller for 24-hour and daytime (-2.1/-1.7 and -2.0/-1.5 mm Hg, respectively, P ≥ 0.22) but greater (P < 0.01) for nighttime (-4.0/-2.8 mm Hg, P ≤ 0.09), especially in sustained uncontrolled hypertension (-5.0/-4.1 mm Hg, P ≤ 0.04) and non-dippers (-6.5/-3.7 mm Hg, P ≤ 0.07), in favor of valsartan/amlodipine. At week 12, PWV was significantly reduced from baseline by valsartan/amlodipine (n = 59, P < 0.0001) but not nifedipine (n = 59, P = 0.06). The changes in PWV were significantly associated with that in ambulatory systolic BP and pulse pressure in the nifedipine (P ≤ 0.0008) but not valsartan/amlodipine group (P ≥ 0.57), with a significant interaction (P ≤ 0.045). The valsartan/amlodipine combination was more efficacious than nifedipine GITS in lowering nighttime BP in sustained uncontrolled hypertension and non-dippers, and in lowering arterial stiffness independent of BP lowering.

Effect of Amlodipine/Valsartan Versus Nebivolol/Valsartan Fixed Dose Combinations on Peripheral and Central Blood Pressure.

INTRODUCTION: Although hypertensive drugs may have the same effect on peripheral blood pressure, they vary in their effect on central blood pressure and its indices. AIM: To evaluate efficacy of fixed-dose combination of amlodipine 10 mg/valsartan 160 mg versus nebivolol 5 mg/valsartan 160 mg in grade 2 or more hypertensive patients assessed by peripheral and central blood pressure. METHODS: A prospective, open label, randomized study done in the outpatient cardiology clinic at Beni-Suef University Hospital. A total of 137 patients continued the study; group I (n = 75) received Amlodipine 10 mg/Valsartan 160 mg (A/V) and group II (n = 62) received Nebivolol 5 mg/Valsartan 160 mg (N/V). Peripheral, central blood pressure and its indices were measured at baseline, after 6 and 12 weeks. RESULTS: The two combinations reduced peripheral and central BP (P < 0.0001) after 6 and 12 weeks. A/V combination significantly reduces central Pulse Pressure (PP) after 6 and 12 weeks (- 8.53 ± 13.80 and - 10.17 ± 11.29 (P < 0.0001) respectively), while N/V showed its efficacy in reducing central PP after 12 weeks (- 7.03 ± 13.10, P = 0.005). A/V combination was more effective in reducing Pulse Wave Velocity (PWV) after 6 and 12 weeks; P < 0.0001 vs P = 0.004. After 6 weeks, N/V was more effective in reducing Augmentation Index (AIx) (- 6.00 ± 10.94 (P = 0.002) vs. - 3.44 ± 9.80 (P = 0.026)) while after 12 weeks A/V did not show any significance (P = 0.085). CONCLUSIONS: Both treatment groups lowered patients' peripheral, central blood pressure after 6 and 12 week of treatment, but Amlodipine/Valsartan combination was more effective. Both treatments exerted different effects on central indices.

A multicenter, randomized, and double-blind phase IV clinical trial to compare the efficacy and safety of fixed-dose combinations of amlodipine orotate/valsartan 5/160 mg versus valsartan/hydrochlorothiazide 160/12.5 mg in patients with essential hypertension uncontrolled by valsartan 160 mg monotherapy.

BACKGROUND: To determine whether the effectiveness and safety of fixed-dose combinations (FDCs) of amlodipine orotate/valsartan (AML/VAL) 5/160 mg are noninferior to those of valsartan/hydrochlorothiazide (VAL/HCTZ) 160/12.5 mg in hypertensive patients with inadequate response to valsartan 160 mg monotherapy. METHODS: This 8-week, active-controlled, parallel-group, fixed-dose, multicenter, double-blind randomized controlled, and noninferiority trial was conducted at 17 cardiovascular centers in the Republic of Korea. Eligible patients had mean sitting diastolic blood pressure (msDBP) ≥90 mm Hg despite monotherapy with valsartan 160 mg for 4 weeks. Patients were randomly assigned to treatment with AML/VAL 5/160 mg FDC (AML/VAL) group or VAL/HCTZ 160/12.5 mg FDC (VAL/HCTZ) group once daily for 8 weeks. A total of 238 patients were enrolled (AML/VAL group, n = 121; VAL/HCTZ group, n = 117), of whom 228 completed the study. RESULTS: At 8 weeks after randomization, msDBP was significantly decreased in both groups (-9.44 ±â€Š0.69 mm Hg in the AML/VAL group and -7.47 ±â€Š0.71 mm Hg in the VAL/HCTZ group, both P < .001 vs baseline). Between group difference was -1.96 ±â€Š1.00 mm Hg, indicating that AML/VAL 5/160 mg FDC was not inferior to VAL/HCTZ 160/12.5 mg FDC at primary efficacy endpoint. Control rate of BP defined as the percentage of patients achieving mean sitting SBP (msSBP) <140 mm Hg or msDBP <90 mm Hg (target BP) from baseline to week 8 was significantly higher in the AML/VAL group than that in the VAL/HCTZ group (84.3% [n = 102] in the AML/VAL group vs 71.3% [n = 82] in the VAL/HCTZ group, P = .016). At 8 weeks after randomization, mean uric acid level was significantly increased in the VAL/HCTZ group compared to that at baseline (0.64 ±â€Š0.08 mg/dL; P < .001). However, it was slightly decreased from baseline in the AML/VAL group (-0.12 ±â€Š0.08 mg/dL; P = .085). The intergroup difference was significant (P < .001). CONCLUSION: The effectiveness and safety AML/VAL 5/160 mg FDC are noninferior to those of VAL/HCTZ 160/12.5 mg FDC in patients with hypertension inadequately controlled by valsartan 160 mg monotherapy.

Electrospun fixed dose formulations of amlodipine besylate and valsartan.

Increasing numbers of elderly people require multi-drug therapies. One route to improve adherence rates is to prepare fixed dose combinations (FDCs), in which multiple active ingredients are loaded into a single formulation. Here, we report the use of electrospinning to prepare fast-dissolving oral FDCs containing amlodipine besylate and valsartan, two drugs prescribed as FDCs for the treatment of hypertension. Electrospun fibers were prepared loaded with one or both drugs, using polyvinylpyrrolidone as the polymer matrix. The fibers were largely cylindrical in morphology and comprise amorphous solid dispersions except with the highest loadings of amlodipine besylate. HPLC demonstrated drug entrapment efficiencies of >85% of the theoretical dose. The mats have folding endurances and thicknesses suitable for use as oral films. The amlodipine besylate-loaded systems are fast-dissolving, with >90% release obtained within 120 s. In contrast, valsartan release from its single-drug formulations took longer, ranging from 360 s to 24 min. With the FDC formulations, rapid release within 360 s was achieved when the loading was 5% w/w of each drug, but again the release time increased with drug loading. Electrospun fibers therefore have significant promise as FDCs, but the target drug and its loading need to be carefully considered.

Association Between Change in Central Nocturnal Blood Pressure and Urine Albumin-Creatinine Ratio by a Valsartan/Amlodipine Combination: A CPET Study.

BACKGROUND: We aimed to assess the association of changes in brachial or central nocturnal systolic blood pressure (SBP) with change in urine albumin-creatinine ratio (UACR) by a valsartan/amlodipine combination (80/5 mg) therapy in hypertensive patients. METHODS: Twenty-three patients (age range, 47-78 years; mean, 68.0 years; 35% men, 65% with chronic kidney disease) with clinic brachial BP ≥140/90 mm Hg were treated with valsartan/amlodipine combination therapy for 16 weeks. At baseline and 16 weeks later, we measured brachial and central nocturnal SBP using an oscillometric Mobil-O-Graph device and UACR by spot urine in 23 patients. RESULTS: The changes in brachial nocturnal SBP (r = 0.445, P = 0.033) and those in central nocturnal SBP (r = 0.616, P = 0.002) were significantly associated with change in UACR by intervention. In multivariable-adjusted multiple regression analyses including changes in both brachial and central nocturnal SBP jointly, only central nocturnal SBP change retained a statistically significant association with change in UACR (ß = 0.919, P = 0.020). CONCLUSIONS: Lowering central nocturnal SBP by a valsartan/amlodipine combination therapy was associated with reduction of UACR, independently of brachial nocturnal SBP reduction. Central nocturnal SBP may be a therapeutic target to protect the kidney. A larger scale interventional study will be needed to confirm the kidney protection conferred by lowering central nocturnal SBP. CLINICAL TRIALS REGISTRATION: Trial Number UMIN000013519.

Efficacy and effectiveness of valsartan/amlodipine and valsartan/amlodipine/hydrochlorothiazide in hypertension: randomized controlled versus observational studies.

OBJECTIVE: The aim of this post-hoc analysis was to compare the results from randomized controlled trials (RCTs) and real-world evidence (RWE) studies of valsartan/amlodipine (Val/Aml) and valsartan/amlodipine/hydrochlorothiazide (Val/Aml/HCTZ) in patients with uncontrolled hypertension (>140/90 mmHg). METHODS: Data was pooled from 15 RCTs (N = 5542) and 8 RWE studies (N = 1397) for Val/Aml; and 2 RCTs (N = 804) and 5 RWE studies (N = 9380) for Val/Aml/HCTZ. Patients who received Val/Aml (80/5, 160/5, 160/10, 320/5, or 320/10 mg), Val/Aml/HCTZ (160/5/12.5, 160/5/25, 160/10/12.5, 160/10/25, or 320/10/25 mg) or placebo were considered for this analysis. Only patients with both baseline and follow-up assessment within 60-90 days after baseline had been included in the analysis. Patients with missing values were excluded from the analysis. Using fitted linear mixed-effects model and random factors, treatment interactions and study design with mean sitting systolic blood pressure (msSBP), diastolic BP (msDBP) and pulse pressure (msPP) reductions from baseline to Week 8-12 of treatment were compared. RESULTS: Baseline demographics and patient characteristics were comparable between RCT and RWE datasets and within Val/Aml and Val/Aml/HCTZ treatment groups. In both RCT and RWE studies, least-squares mean (LSM) reduction in msSBP/msDBP and msPP from baseline were significant (p < .05) across all dosages. The efficacy of Val/Aml in RCTs was statistically significantly greater than in RWE studies for msSBP/msDBP (-23.1/-13.8 vs. -17.9/-9.1 mmHg) but the difference was non-significant for msPP (-8.6 vs. -9.3 mmHg; p = .77). For Val/Aml/HCTZ, no direct comparison was available but a similar trend was observed. The difference observed for msSBP and msDBP may be due to routine practice setting, larger populations may have more confounders and different behaviors towards treatment adherence. CONCLUSION: These findings demonstrate that the efficacy of Val/Aml and Val/Aml/HCTZ in RCTs was more pronounced compared with their effectiveness in RWE studies in different ethnic populations although the overall benefit was not different.

Comparison of morning vs bedtime administration of the combination of valsartan/amlodipine on nocturnal brachial and central blood pressure in patients with hypertension.

The aim of this study was to compare the effect of morning and bedtime administration of valsartan/amlodipine combination therapy (80/5 mg) on nocturnal brachial and central blood pressure (BP) measured by ambulatory BP monitoring in patients with hypertension. This was a 16-week prospective, multicenter, randomized, open-label, crossover, noninferiority clinical trial. Patients underwent 24-hour ambulatory BP monitoring at randomization, at switching, and at the end of the study. Twenty-three patients (mean age, 68.0 years) were studied. The difference in nocturnal brachial systolic BP between the morning and bedtime administrations of combination valsartan/amlodipine was -3.2 mm Hg, and the two-sided 95% confidence interval ranged from -6.8 to 0.4 mm Hg. The difference in nocturnal central systolic BP was -4.0 mm Hg (95% confidence interval, -7.6 to -0.4 mm Hg). The upper limit of the 95% confidence interval was below the margin of 3.0 mm Hg in both nocturnal brachial and central systolic BP, confirming the noninferiority of morning administration to the bedtime administration of valsartan/amlodipine combination therapy.

Analytical methodology for the electro-catalytic determination of estradiol and progesterone based on graphene quantum dots and poly(sulfosalicylic acid) co-modified electrode.

The goal of this study was to develop an electroanalytical method for the simultaneous determination of steroid hormones for the first time. The key factor in the electrochemical methods is the choice of suitable electrode materials. For this purpose, graphene quantum dots (GQDs) doped poly(sulfosalicylic acid) (PSSA) was immobilized on a glassy carbon electrode (GCE). Apart from exhibition strong and stable electrocatalytic response towards estradiol (E2) and progesterone (P4), the proposed sensor was able to distinguish two hormone's oxidation peaks clearly. Under the optimal conditions, for selective determination of E2, good linear relationships were obtained in the range of 0.001-6.0µmolL-1, with detection limit of 0.23nmolL-1, and for P4 in the range of 0.001-6.0µmolL-1, with the detection limit of 0.31nmolL-1. The prepared sensor possessed accurate and rapid response toward E2 and P4 with an improved stability, selectivity and repeatability. More importantly, the facile and environment-friendly electrochemical construction strategy provided here, may be open a cost-effective way for setting up nanocomposites or nanohybrid-based sensing platform, which extend the application of electrochemical sensor for the green, facile and sensitive analysis of electroactive compounds in biological systems and pharmaceutical formulations.

Effectiveness and safety of valsartan/amlodipine in hypertensive patients with stroke: China Status II subanalysis.

High blood pressure (BP) is a major risk factor associated with stroke in China. This is a subanalysis of patients from the China Status II study, aimed to evaluate the effectiveness and safety of valsartan/amlodipine (Val/Aml) single-pill combination (SPC) in hypertensive patients with different stroke subtypes (hemorrhagic, ischemic, or mixed).China Status II was a multicenter, postmarketing, prospective observational study in hypertensive patients uncontrolled on monotherapy. The study was an 8-week open-label treatment period with 2 4-week follow-ups. Change in BP from baseline to weeks 4 and 8, BP control rate, and response rate at weeks 4 and 8, and safety of 8-week treatment with Val/Aml (80/5 mg) were assessed.A total of 565 hypertensive patients with different types of stroke were analyzed in this China Status II substudy. Significant mean sitting systolic/diastolic BP (MSSBP/MSDBP) reductions from baseline to week 8 were observed across all stroke subtypes (P < .0001). At week 8, percentages of patients achieving MSSBP response (≥20 mm Hg reduction from baseline) were 76.3%, 74.4%, and 85.7%, MSDBP response (≥10 mm Hg reduction from baseline) were 67.8%, 65.9%, and 64.3%, and BP control (<140/90 mm Hg) were 74.6%, 80.5%, and 92.9%, in the hemorrhagic, ischemic, and mixed stroke subgroups, respectively. Adverse events (AEs) and serious AEs were reported in 5 patients (1%) and 1 patient (0.2%), respectively, in the ischemic stroke subgroup, while no AEs were reported in hemorrhagic and mixed stroke subgroups.Val/Aml SPC was effective in hypertensive patients with different stroke subtypes and was well tolerated.

Neprilisina: indicaciones, expectativas y retos / Neprilysin: indications, expectations, and challenges

No disponible

[DYNAMICS OF THE CIRCADIAN BLOOD PRESSURE PROFILE DURING COMBINED AMLODIPINE-VALSARTAN THERAPY IN FAR NORTH RESIDENTS].

The aim of the work was to study dynamics of daily arterial pressure profile during combined antihypertensive therapy starting from calcium and angiotensin II antagonists (amlodipine-valsartan) in Far North employees suffering arterial hypertension engaged on different working schedules. A total of 137 patients with grade I-III AH were divided into 2 groups. Those in group 1 worked day shifts (n=70) and the remaining ones worked night shifts (group 2). 129 patients completed the course of therapy. The final mean daily doses of amlodipine-valsartan were 8.2 ± 1.1/144.8 1.8 and 9.4 ± 1.6/197.8 ± 3.5 mg in groups I and 2 respectively. AP monitoring was performed before, 4 weeks and 6 months after therapy. Six months after the onset of amlodipine-valsartan therapy 97.2 and 97.6% of the patients in groups 1 and 2 respectively showed the target AP level and normalization of daily AP profile. Daily variability of AP in group 2 (excepting night-time variability) was also normal. Morning AP dynamics markedly improved in both groups. Most patients demonstrated excellent compliance with therapy due to its high efficacy and good tolerability.

Effectiveness of Valsartan/Amlodipine Single-pill Combination in Hypertensive Patients With Excess Body Weight: Subanalysis of China Status II.

Obesity is a major global health concern and is associated with hypertension. However, there is a lack of studies evaluating the effectiveness of valsartan/amlodipine single-pill combination in Chinese hypertensive patients with excess body weight uncontrolled by monotherapy. To evaluate this effectiveness and its association with obese categories, we performed a prespecified subanalysis and a post hoc analysis of patients from China status II study. In this subanalysis, 11,289 and 11,182 patients stratified by body mass index (BMI) and waist circumference (WC), respectively, were included. Significant mean sitting systolic and diastolic blood pressure (BP) reductions from baseline were observed at week 8 across all BMI and WC subgroups (P < 0.001). The percentages of patients achieving BP control were 65.2%, 62.8%, and 64.5% (men 64.5% and women 64.4%) in the overweight, obesity, and abdominal obesity subgroups, respectively. The positive association between BP control and obese categories could only be found in subgroups stratified by BMI other than WC. Our study demonstrated the effectiveness of valsartan/amlodipine single-pill combination in Chinese hypertensive patients with excess body weight uncontrolled by monotherapy, and its effectiveness was better associated with BMI than WC.

Choice of Antihypertensive Combination Therapy Based on Daily Salt Intake.

BACKGROUND: It is unclear whether thiazide diuretics (TZs) or calcium channel blockers (CCBs) are more effective as add-on therapy to angiotensin receptor blockers (ARBs) in controlling hypertension. Because TZs are a rational choice in salt-sensitive hypertension, patients with high salt intake might preferentially benefit from ARB/TZ over ARB/CCB combination therapy. METHODS: Hypertensive patients who failed to reach blood pressure goals despite treatment with ARBs alone were randomly assigned to receive either ARB/TZ or ARB/CCB combination therapy. Estimated daily sodium intake was calculated from spot urine values of sodium and creatinine. RESULTS: Blood pressure was measured at baseline, and at 4, 8 and 12 weeks after starting combination therapy. For all study patients (n = 87), diastolic blood pressure reduction was greater in patients receiving ARB/CCB treatment. However, in the 37 patients with a baseline estimated daily salt intake greater than 10 g and baseline systolic blood pressure (SBP) ranging from 150 to 200 mm Hg, SBP was lower (P < 0.05) and SBP reduction was greater (P < 0.05) 4 weeks after starting combination therapy in those receiving ARB/TZ treatment. In the 31 patients whose estimated daily salt intake increased at 12 weeks compared with baseline, SBP at 12 weeks was lower in those receiving ARB/TZ treatment (P < 0.05). CONCLUSIONS: Estimated daily salt intake is a useful tool for guiding antihypertensive therapy and should be measured repeatedly during the therapeutic course.

Mixed amlodipine/valsartan overdose treated by the molecular adsorbent recirculating system (MARS™).

CASE REPORT: We describe the case of a 58-year-old woman who developed a severe distributive shock following the intentional ingestion of a large overdose of amlodipine (480 mg) combined with valsartan (3680 mg). Extreme vasoplegia remained refractory to maximal standard therapy including fluid resuscitation, intravenous calcium, vasopressors at very high doses, hyperinsulinemia-euglycemia therapy, lipid emulsion, and methylene blue administration. Besides, the patient exhibited hyperglycemia refractory to very high doses of insulin. Due to its theoretical ability to effectively remove protein-bound drugs such as amlodipine from the circulation, albumin dialysis with the molecular adsorbent recirculating system (MARS™) was performed during two consecutive sessions. Blood was drawn for toxicokinetic calculations. Amlodipine elimination half-life during the first MARS™ session was calculated at 7.6 h. In addition, there was a rapid fall in blood glucose, requiring the introduction of a continuous infusion of glucose in order to achieve euglycemia. Moreover, a few hours after the initiation of the MARS™ therapy, the hemodynamic status was not significantly modified but a significant tapering of epinephrine infusion was possible, together with a progressive decrease of blood lactate level. However, the need for vasopressors in decreasing doses was present until day 5 post-ingestion. Eventually, the patient fully recovered and was discharged home 8 days after admission. DISCUSSION: The role of the MARS™ in the treatment of severe poisoning of calcium channel blockers is still to be defined. We were able to demonstrate a relatively short elimination half-life of amlodipine. A decreased insulin resistance and a reduction of epinephrine infusion were also observed.