Effects and Safety of Allisartan Isoproxil Combined With Amlodipine or Indapamide in Patients With Hypertension Who Failed Allisartan Monotherapy

Background To primarily evaluate the effects and safety of a selective angiotensin II type 1 (AT1) receptor blocker (ARB) allisartan isoproxil combined with amlodipine or indapamide in the treatment of patients with essential hypertension who failed allisartan monotherapy. Methods Patients aged 18–75 years with mild-to-moderate essential hypertension [office systolic blood pressure (SBP) 140 to <180 and/or office diastolic blood pressure (DBP) 90 to <110 mm Hg] in 44 study centers between 2016 and 2018 were recruited. Allisartan isoproxil tablet 240 mg was administered per day for 4 weeks, and continued for 8 weeks if office blood pressure (BP) achieved the target of SBP/DBP <140/90 mm Hg. The nonachievers were 1:1 randomly divided into allisartan isoproxil 240 mg + indapamide sustained-release tablet 1.5 mg, or allisartan isoproxil 240 mg + amlodipine besylate 5 mg groups for further 8 weeks of combined therapy. The BP target achieving rate, reduction of sitting BP from baseline, safety and compliance were evaluated as the primary efficacy endpoint. Results A total of 2,212 patients were enrolled, among them 2,126 patients were included in the efficacy analysis, with an average age of 55.1 ± 10.2 years. A total of 1,463 cases (68.8%) were effective after 4 weeks allisartan treatment, and the mean SBP and DBP were significantly decreased by 14.7 ± 12.2 and 8.0 ± 8.4 mm Hg compared with the baseline levels (all P < 0.001). In nonachievers, allisartan combined with indapamide for 8 weeks significantly lowered the sitting BP (SBP/DBP) by 14.0 ± 12.2/8.3 ± 9.2 mm Hg, respectively, compared with 4 weeks monotherapy with allisartan with a BP targeting rate of 57.7% (169/293). In the allisartan + amlodipine group, the SBP/DBP were significantly decreased by (14.4 ± 12.1/8.2 ± 8.2) mm Hg, respectively, with a BP targeting rate of 62.8% (181/288). There was no statistical significance in BP reduction, targeting rate, or adverse reactions between the 2 combined therapies. Conclusions Allisartan isoproxil combined with indapamide or amlodipine can further improve the BP targeting rate when allisartan monotherapy failed in essential hypertension. The 2 combined therapies have similar efficacy and safety.

Comparing the Apelin Level in Hypertensive Patients Who Received Hypertension Drugs

Background: Apelin, an adipokine secreted from adipose tissue, plays an important role in regulating blood pressure and hypertension. Objectives: The current study aimed to compare the plasma Apelin level in hypertensive patients under treatment with amlodipine, losartan, and amlodipine + losartan. Methods: In this case-control study, the serum level of Apelin was compared in four groups of (A) Healthy subjects (n = 31); (B) Hypertensive patients, received amlodipine (n = 31); Hypertensive patients, received losartan (n = 45); and patients (n = 33) that received amlodipine and losartan. Apelin level in serum samples was measured using Human Apelin ELISA Kit according to the manufacturers’ instructions. Data were analyzed using SPSS version 19 (Chicago: SPSS Inc.), at the significant level of α = 0.05. Results: The mean blood level of Apelin in the control group and groups receiving amlodipine, losartan, and amlodipine + losartan was 366.16 ± 36.04, 247.19 ± 27.77, 282.93 ± 47.08, and 289.84 ± 32.20 g/dl, respectively. Losartan + amlodipine group had a higher level of Apelin compared with amlodipine alone (P < 0.05). Conclusions: This study demonstrated that Apelin has a definite protective effect in preventing hypertension. Also, according to the results, the renin-angiotensin-aldosterone system inhibitors, such as losartan, caused a higher increase in the Apelin, resulting in better blood pressure control.

COMPARATIVE EVALUATION OF THERAPEUTIC EFFECT OF MOXONIDINE VERSUS AMLODIPINE ON BLOOD PRESSURE IN OBESE HYPERTENSIVES

Background: High blood pressure is frequently associated with metabolic alterations such as insulin resistance, impaired glucose tolerance, dyslipidaemia and obesity. Moxonidine, a selective imidazoline receptor agonist, reduces activity of sympathetic nervous system and lowers blood pressure, and has been shown to have benecial effects on lipid and carbohydrate metabolism. The present study has been conducted to evaluate antihypertensive efcacy of moxonidine and compare it with amlodipine in mild to moderate hypertension in obese patients. Methods: This was an open-label randomized study. Patients were divided into two groups of 50 patients each, rst group was given amlodipine 5 mg daily and the second group was given moxonidine 0.2 mg once daily. At the end of 8 weeks, the therapeutic effects of both regimes on blood pressure in obese patients with stage 1 and stage 2 hypertension were compared and also with lipid prole, fasting sugars and microalbuminuria. Results: The study involved 100 participants with a mean age of 51.12±6.25 years and 48.88±5.15 years in moxonidine group and amlodipine group, respectively. Systolic and diastolic blood pressure reduction was signicant in both groups at 8-weeks (p<0.001). The reduction in FBS (p=0.008), total cholesterol (p=0.04), serum triglycerides (p<0.001) and increase in HDL (p=0.02) were all signicant in moxonidine group, but LDL reduction was not signicant. In amlodipine group, change in FBS, total cholesterol, serum triglycerides, HDL and LDL levels were all insignicant. There was also signicant reduction in microalbuminuria in moxonidine group. Conclusion: Moxonidine and amlodipine are equally effective antihypertensives and safe in obese hypertensives. Moxondine has additional favourable effects on lipid prole (serum cholesterol, TGs and LDL), fasting blood glucose and microalbuminuria.

Effects of different enantiomers of amlodipine on lipid profiles and vasomotor factors in atherosclerotic rabbits

This research aimed to describe the functions of vascular endothelial cells (VECs) in protecting target organs and the anti-atherosclerotic effects of different enantiomers of amlodipine on a rabbit model of atherosclerosis. Thirty male New Zealand white rabbits were randomly allocated to four groups (nA = 9, nB = 7, nC = 7, and nD = 7 rabbits): rabbits in group-A (control group) were fed a high-fat diet, group-B rabbits were fed a high-fat diet plus 2.5 mg/kg/day S-amlodipine, group-C rabbits were fed a high-fat diet plus 2.5 mg/kg/day R-amlodipine, and group-D rabbits were fed a high-fat diet plus 5 mg/kg/day racemic amlodipine. Different enantiomers of amlodipine did not influence lipid profiles and serum level of eNOS in the rabbit atherosclerosis model but decreased ET-1 expression to some extent. The serum NO and iNOS levels in the drug intervention groups were significantly reduced. No significant differences in the rabbits’ body weights were observed. At the 4th and 8th weeks, the serum lipid profiles significantly increased in high cholesterol diet groups. The serum ET-1 level was significantly increased in each group of rabbits at the 8th week. Both S-amlodipine and R-amlodipine may protect the endothelium by reducing the serum ET-1 level, downregulating iNOS expression.

Effects of L-/N-Type Calcium Channel Blockers on Angiotensin II–Renin Feedback in Hypertensive Patients

Objectives. Cilnidipine, an L-/N-type calcium channel blocker (CCB), has unique organ-protective properties due to suppression of hyperactivity in the sympathetic nervous system and renin-angiotensin system (RAS). In this study, we hypothesized that cilnidipine might exert a renoprotective effect by suppressing the RAS. Methods. A total of 25 hypertensive patients receiving a RAS inhibitor were randomly assigned to a cilnidipine (n = 12) or amlodipine (n = 13) group. The effects of cilnidipine on proteinuria and angiotensin II–renin feedback were assessed. Results. After 6 months of treatment, both systolic and diastolic blood pressures were significantly reduced to a similar extent in both groups. The urine albumin-to-creatinine ratio was significantly lower in the cilnidipine group ( p < 0.05 ) than in the amlodipine group. Amlodipine increased plasma angiotensin I and angiotensin II levels ( p < 0.05 ), whereas cilnidipine did not. Interestingly, the cilnidipine group had a higher ratio of angiotensin-(1–7) (Ang-(1–7)) to angiotensin II in plasma than the amlodipine group ( p < 0.05 ). Conclusions. The L-/N-type CCB cilnidipine, but not amlodipine, decreased urinary albumin excretion in hypertensive patients. Cilnidipine also increased the ratio of Ang-(1–7) to angiotensin II in plasma, which might be one factor underlying its beneficial effects.

The Effects of Telmisartan and Its Combinations on Office Blood Pressure: Results of Prospective Observational Study TAINA

Aim. To evaluate the effectiveness and safety of telmisartan, used in monotherapy or in combination with hydrochlorothiazide or amlodipine, in real clinical practice in patients with diagnosed arterial hypertension who have not reached the target levels of blood pressure (BP).Material and methods. The study was a non-intervention, prospective, multicenter, comparative, observational, epidemiological program, which was carried out in Russian medical institutions. The total patient population in which the prescribed therapy was administered included 1933 people (758 men and 1175 women, mean age 57.0-59.3 years). Participants were followed-up for 12 weeks. The change in office BP was evaluated on the 4th and 12th week.Results. Significant (p<0.001 in all cases) change in office BP compared with the initial data were recorded in all study groups of therapy already at 4 weeks of treatment and became even more pronounced at 12 weeks. In the telmisartan monotherapy group, BP decreased from 155.7±10.7/92.2±7.6 mm Hg to 131.4±12.1/80.8±7.3 mm Hg at the end of the 4th week and to 125.3±7.6/78.2±6.1 mm Hg – at the end of the 12th week. Similarly, after treatment with the combination of telmisartan and hydrochlorothiazide, BP decreased from 162.7±12.6/94.3±7.9 mm Hg to 133.2±12.5/81.6±8.4 mmHg at the end of the 4th week and to 126.0±7.8/78.4±6.7 mm Hg – at the end of the 12th week. In telmisartan/amlodipine group, a decrease in BP also occurred, from 162.5±13.2/94.6±8.6 mm Hg to 132.8±14.5/81.3±7.5 mm Hg on the 4th week and to 125.4±8.7/78.4±5.6 mm Hg at the end of follow up (12 weeks). The proportion of patients who reached the target BP (<140/90 mm Hg) after treatment with telmisartan as monotherapy was 91.7%, after treatment with telmisartan+hydrochlorothiazide – 89.6%, after treatment with telmisartan+amlodipine – 92.8%. Throughout the program, prescribed therapy was well tolerated by patients. During the study, 47 adverse events (AEs) were recorded in 36 patients: 31 AEs with telmisartan monotherapy, 5 AEs with telmisartan/hydrochlorothiazide combination, and 11 AEs with telmisartan/amlodipine combination. Most of the AEs registered during the trial resolved by the end of the study, in four cases the date of AEs resolve is unknown, in two cases, at the time of completion of the study, AEs continued.Conclusion. In the TAINA study a high antihypertensive efficacy and a comparable favorable safety and tolerability profile of telmisartan, used as monotherapy and in combination with hydrochlorothiazide or amlodipine was determined.

Comparison of Blood Pressure Variability Between Losartan and Amlodipine in Essential Hypertension (COMPAS-BPV)

BACKGROUND Antihypertensive therapy using renin–angiotensin system blockers and calcium channel blockers to target blood pressure variability (BPV) has not yet been established. We aimed to compare the ability of losartan and amlodipine to lower BPV and systolic blood pressure (SBP) in essential hypertensive patients. METHODS Patients were randomly assigned either losartan 50 mg or amlodipine 5 mg. Medications were uptitrated and hydrochlorothiazide was added according to protocol for 6 months. The primary endpoint was the office visit-to-visit SD of SBP. The secondary endpoints included average real variability (ARV), office SBP, and home SBP. RESULTS The losartan group (n = 71) and amlodipine group (n = 73) finished the scheduled visits between April 2013 and May 2017. The office visit-to-visit SD of SBP was comparable between the losartan and amlodipine groups (11.0 ± 4.2 vs. 10.5 ± 3.8, P = 0.468). The office visit-to-visit ARV of SBP was significantly elevated in the losartan group (10.6 ± 4.3 vs. 9.1 ± 3.4, P = 0.02). The absolute SBP decrement from baseline to 6 months was similar between groups, although the office mean SBP at 6 months was higher in the losartan group (132.3 ± 12.9 vs. 127.5 ± 9.0 mm Hg, P = 0.011). In home blood pressure analysis, evening day-to-day BPV indexes (SD and ARV) were significantly higher in the losartan group at 6 months. CONCLUSIONS The lowering effect of the office visit-to-visit SD of SBP was similar between losartan and amlodipine. However, the losartan group showed a higher office visit-to-visit ARV of SBP and evening day-to-day home BPV indexes. Therefore, amlodipine may be better to lower BPV in essential hypertensive patients.

Evaluation of losartan plus hydrochlorothiazide combination therapy against amlodipine monotherapy in patients of hypertension

Background: Microalbuminuria has been shown to predict cardiovascular disease (CVD) in patients with hypertension. Recently the FDC of losartan and hydrochlorothiazide (HCTZ) has been reported to be effective for achieving a target BP level and also improvement in cardiovascular prognosis. The present study was conducted to compare effect of losartan plus hydrochlorothiazide combination therapy and high dose amlodipine monotherapy on blood pressure and microalbuminuria.Methods: Total 184 patients with hypertension were randomly allocated to two groups. The patients in group 1 received Amlodipine 5 mg orally for first 4 weeks. The patients from group 2 received losartan 50 mg orally for first 4 weeks. Patients in group 1 were titrated to amlodipine 10 mg orally for next 4 weeks. The patients in group 2 were titrated to FDC of losartan (50 mg) plus HCTZ (12.5 mg) for next 4 weeks. Follow–up visits were scheduled at 4 weeks and 8 weeks. Pulse rate, sSBP and sDBP were estimated at each follow–up. Microalbuminuria was estimated at 8 weeks.Results: There was no significant difference in mean change in sSBP, sDBP and pulse rate between two treatment groups (p>0.05). There was greater reduction in microalbuminuria in group 2 patients (p<0.0001). The adverse effects such as flushing and lower extremity oedema were significantly more in amlodipine group (p<0.05).Conclusions: Losartan plus HCTZ has similar effect on BP, better safety profile and superior effect on microalbuminuria level reduction.

Amlodipine and valsartan improving effect on the survival rate and deleterious pathological changes in streptozotocin-induced diabetic rats treated with metformin

Diabetes mellitus (DM) and hypertension usually co-exist, and when this happens, the prognosis would be worse than each disease alone. Given this, we evaluated the possible effects of valsartan and amlodipine administration on metformin-treated diabetic rats models induced by streptozotocin. Male Wistar rats (200–350 g) were fasted overnight. Then, we induced DM by administrating a single dose of 40 mg/kg streptozotocin (IP), which was confirmed after 48 h. Animals with blood sugar ≥ 200 mg/dl were considered diabetic and divided into four diabetic groups of untreated diabetic animals (Group B), diabetic animals treated with metformin (Group C), diabetic animals treated with metformin plus amlodipine (Group D), and diabetic rats treated with metformin plus valsartan (Group E). There was also a group A, consisting of normal rats with no drug treatment. After six weeks of treatment, we sacrificed the animals under chloroform anesthesia, and their blood samples were collected for hematological and biochemical analyses. The mortality rate in untreated diabetic rats was 100% before 6 weeks, but anti-diabetic treatment (metformin) significantly (P < 0.05) improved the survival rate and controlled their blood glucose level. The addition of antihypertensive drugs (amlodipine and valsartan) enhanced this curative effect. The various treated groups showed ameliorations in pathologic changes and biochemical indices, as well as, evidence of organ protection, compared with the untreated diabetic group. The study showed that adding an antihypertensive drug (amlodipine or valsartan) to metformin regimen improved outcomes in diabetic rats compared to using metformin alone.

A PROSPECTIVE CLINICALTRIAL OF AMLODIPINE IN COMPARISON TO PERINDOPRIL

Objective: The objective of this research was to perform a prospective clinical trial to compare antihypertensive effects of amlodipine and perindopril in hypertensive patients.Methods: In our study, we compared antihypertensive effects of well tolerated and commonly used antihypertensive drugs, amlodipine and perindopril. There were 81 hypertensive patients of both sexes over 40 y of age without other diseases included in this prospective clinical trial. Forty (40) patients were treated with amlodipine (5 mg/day) and forty-one (41) patients were treated with perindopril (4 mg/day). After one month of taking both drugs, blood pressure was measured in the supine position with a standard mercury sphygmomanometer in the morning.Results: Amlodipine and perindopril groups were having almost similar characteristics at the beginning of the study. There was significantly decrease insystolic blood pressure (sBP) throughout the study period in the amlodipine group (p≤ 0.05) but not in the perindopril group. The efficacy of amlodipine over perindopril on systolic blood pressure and diastolic blood pressure (dBP) was significant (p≤ 0.001 for sBP and p≤ 0.05 for dBP).Conclusion: It may be concluded that the antihypertensive efficacy of amlodipine was superior when compared to perindopril.