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)

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.

Pharmacokinetics and safety of highly variable valsartan in single-pill combination with amlodipine versus its generic formulation: a randomized, three-cycle, three-sequence, partially replicated crossover phase I bioequivalence clinical trial.

Valsartan/amlodipine (I) is a single-pill combination (SPC) of an angiotensin II receptor blocker (ARB) and a calcium channel blocker (CCB) for treating hypertension. A clinical trial was performed to demonstrate that the test and reference valsartan/amlodipine formulations were bioequivalent under fasting and postprandial conditions. Participants were randomly divided into three sequences at a ratio of 1:1:1 for three-cycle, reference formulation replicated, crossover administration. The average bioequivalence (ABE) and reference-scaled average bioequivalence (RSABE) methods were used to evaluate BE using the main pharmacokinetic (PK) parameters. Overall, 45 eligible participants were enrolled in the postprandial trial, which was consistent with the fasting trial. For valsartan, the RSABE method was used to evaluate the BE of Cmax, while the ABE method was applied to evaluate the BE of AUC0-t and AUC0-∞. Both point estimates and 95% upper confidence bound met the BE criteria. For amlodipine, the ABE method was performed, and the 90% confidence intervals of the geometric mean ratios (GMR) for Cmax and AUC0-72 h were all within 80%-125%, with the BE criteria being met. Therefore, the two formulations are bioequivalent and have similar safety profiles in healthy Chinese subjects. Clinical trial registration: [http://www.chinadrugtrials.org.cn/index.html], identifier [CTR20210214].

Efficacy and safety of Tengfu Jiangya tablet combined with valsartan/amlodipine in the treatment of stage 2 hypertension: study protocol for a randomized controlled trial.

BACKGROUND: The prevalence rate of hypertension in the Chinese population is on the rise, and the control rate of hypertension is low. International guidelines, including the 2018 Chinese Guidelines for the Management of Hypertension, recommend optimized drug selection and combination therapy for patients with stage 2 hypertension and blood pressure ≥ 160/100 mmHg, including valsartan/amlodipine (Val/Aml). The traditional Chinese medicine (TCM) compound Tengfu Jiangya tablet (TJT; No. Z20110021, Shandong Provincial Food and Drug Administration) is prepared in the medical institution of Affiliated Hospital of Shandong University of Traditional Chinese Medicine. It is an effective compound preparation of TCM for the treatment of hypertension in the national clinical research base of TCM. The aim of this study was to evaluate the efficacy and safety of TJT combined with Val/Aml in the treatment of stage 2 hypertension with hyperactivity of liver yang. METHODS: This randomized double-blind, placebo-controlled, multicenter trial will be conducted with a total of 288 participants with stage 2 hypertension at seven clinical trial centers. The stratified random method will be used, and the subcenter will be taken as the stratification factor. Eligible patients will be randomly assigned (1:1) into groups receiving either TJT or placebo three times daily for 28 days, both combined with Val/Aml 80/5 mg. The primary efficacy endpoint is the reduction in the mean sitting systolic blood pressure (msSBP) and the mean sitting diastolic blood pressure (msDBP) from baseline to week 4. Adverse events and laboratory test results will be monitored throughout the trial. DISCUSSION: This is the first placebo-controlled randomized trial conducted to evaluate the efficacy and safety of a Chinese herbal extract combined with Val/Aml in patients with stage 2 hypertension. Our study may help to provide evidence-based recommendations of a complementary preventive measure for stage 2 hypertension. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000030611 . Registered on 8 March 2020.

China STudy of valsartan/amlodipine fixed-dose combination-bAsed long-Term blood pressUre management in HypertenSive patients: a one-year registry (China STATUS III).

Objective: The present observational study evaluated long-term management of hypertension in patients who received treatment with valsartan and amlodipine in a single-pill combination (Val/Aml SPC) in a real-world setting in China (Chinese Clinical Trial Registry number ChiCTR1900021324). Methods: This was a prospective, observational, multicenter, real-world registry study wherein patients with hypertension who had already received Val/Aml SPC (80/5 mg) for at least 4 weeks before study enrollment were observed for 1 year. Investigators recorded patient data every 3 months and essentially five times during the 1 year follow-up period. Effectiveness was assessed by the blood pressure (BP) control rate and average duration of treatment at the end of the study. Safety was monitored by the incidence of adverse events (AEs) and serious adverse events (SAEs). Results: Overall, 985 patients were enrolled (mean ± standard deviation [SD] age: 60.3 ± 11.5 years); of these, 894 were included in the full analysis set, 758 of whom completed the study. At baseline, BP was controlled (<140/90 mmHg) in 64.3% of patients on Val/Aml SPC for at least 4 weeks before enrollment. Office BP control rates significantly improved from baseline in 74.1% of patients at 1 year (p < .0001). Overall, 575 (87.0%) patients remained on Val/Aml SPC at 1 year (average exposure: 311.5 days). AEs were reported in 23.3% of patients. The majority of AEs were mild to moderate, and 0.6% of patients discontinued Val/Aml SPC because of SAEs. Conclusion: This study provides evidence that Val/Aml SPC effectively reduced BP over the long term among Chinese hypertensive patients, with a good adherence and tolerability profile, and that most hypertensive patients may benefit from this combination.

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.

Long-term Follow-up Study on Valsartan and Amlodipine Tablets(Ⅰ)on Blood Pressure Control and Re-nal Protection of Patients with Refractory Hypertension / 中国药房

OBJECTIVE:To study the effect of long-term follow-up of Valsartan and amlodipine tablets(Ⅰ)on blood pressure control and renal protection of patients with refractory hypertension. METHODS:120 patients with refractory hypertension were di-vided into control group and observation group according to the patients’wishes,with 60 cases in each group. All patients accepted the triple therapy of amlodipine+valsartan+hydrochlorothiazide and life-style intervention;at the time of discharge from hospital, the blood pressure was well controlled. After discharge from hospital,control group was given amlodipine;observation group was given Valsartan and amlodipine tablet (Ⅰ) orally,1 tablet each time,qd,and dose increasing according to blood pressure,with maximal dose no more than 2 tablets. With 18 months of follow-up,blood pressure and renal function indexes of 2 groups were ob-served at different time points,and blood pressure control rate and the rate of renal function injury were also observed at the last follow-up;the occurrence of ADR was observed. RESULTS:2 cases and 3 cases were follow-up loss in observation group and con-trol group,respectively. With 12 and 18 months of follow-up,24 h systolic pressure,24 h diastolic pressure and 24 h urine protein of 2 groups increased significantly while creatinine clearance rate decreased significantly compared with before discharge;but the in-dexes of observation group was better than that of control group,with statistical significance(P0.05). CONCLUSIONS:Valsartan amlodipine tablet(Ⅰ)has obvi-ous advantages in long-term follow-up of blood pressure control of patients with refractory hypertension. It can significantly reduce the incidence of renal function injury with good safety.

Effect of valsartan/amlodipine compound preparation on patients with hypertension / 中国生化药物杂志

Objective To investigate clinical therapeutic effect of valsartan/amlodipine compound preparation on patients with hypertension. Methods From Juue 2011 to June 2013, a total of 110 columns with hypertension as the research object, according to randomly divided into two groups.Valsartan/amlodipine compound preparation(group A) and amlodipine combined with metoprolol group(group B), continuous administration for 24 weeks, patients symptoms, former state, improve heart function and blood clots compared curative effect were monitored.Results After 24 weeks of treatment with valsartan/amlodipine compound preparation group, compared with group B, SBP and DBP were decreased significantly, the TC, TG and Glu content were also decreased significantly, clinical symptoms improved ratio was 90.91%(P<0.05).Cardiac function improvement recovery was 89.09%(P<0.05).D-Dimer level was decreased significantly(P<0.05), the former state blood clots were effectively prevented.Conclusion The high blood pressure in treatment with valsartan/amlodipine compound preparation has more therapy advantages in clinical treatment .