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A randomized, double-blind clinical trial to evaluate the efficacy and safety of a fixed-dose combination of amlodipine/rosuvastatin in patients with dyslipidemia and hypertension.
Kim, W, Chang, K, Cho, EJ, Ahn, JC, Yu, CW, Cho, KI, Kim, YJ, Kang, DH, Kim, SY, Lee, SH, et al
Journal of clinical hypertension (Greenwich, Conn.). 2020;(2):261-269
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Abstract
This multicenter, randomized, double-blind, parallel-group phase III clinical trial aimed to investigate the efficacy and safety of a rosuvastatin + amlodipine combination compared with that of rosuvastatin or amlodipine monotherapy in hypertensive patients with dyslipidemia. A total of 106 patients of 15 institutions in Korea were randomly assigned to 1 of 3 treatment groups: rosuvastatin 20 mg + amlodipine 10 mg, amlodipine 10 mg, or rosuvastatin 20 mg. After 8 weeks of treatment, the mean ± SD of change in mean sitting systolic blood pressure (msSBP) was -22.82 ± 12.99 mm Hg in the rosuvastatin + amlodipine group, the most decreased among the treatment groups. The percentage of patients whose msSBP decreased ≥20 mm Hg or msDBP decreased ≥10 mm Hg was also highest in this group (74.29%). The mean ± SD percentage change in low-density lipoprotein cholesterol (LDL-C) level from baseline after 8 weeks was -52.53% ± 11.21% in the rosuvastatin + amlodipine group, the most decreased among the treatment groups. More patients in the rosuvastatin + amlodipine group achieved their target LDL-C goal at 8 weeks, compared with the other treatment groups (97.14%). No serious adverse events or adverse drug reactions were observed in all groups. In hypertensive patients with dyslipidemia, combination treatment with rosuvastatin 20 mg + amlodipine 10 mg effectively reduced blood pressure and LDL-C levels while maintaining safety.
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Efficacy of a new single-pill combination of a thiazide-like diuretic and a calcium channel blocker (indapamide sustained release/amlodipine) in essential hypertension.
Dominiczak, AF, de Champvallins, M, Brzozowska-Villatte, R, Asmar, R, ,
Journal of hypertension. 2019;(11):2280-2289
Abstract
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.
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Long-term effect of the perindopril/indapamide/amlodipine single-pill combination on left ventricular hypertrophy in outpatient hypertensive subjects.
Mazza, A, Townsend, DM, Schiavon, L, Torin, G, Lenti, S, Rossetti, C, Rigatelli, G, Rubello, D
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2019;:109539
Abstract
BACKGROUND Most antihypertensive drugs used in monotherapy or in combination therapy reduce the left ventricular mass index (LVMI). However, little is known about the effects on LVMI of a triple fixed-dose combination (TFC) therapy, containing in a single pill an angiotensin-converting enzyme inhibitor (ACEI), a diuretic and a calcium channel blocker (CCB). METHODS In this prospective open-label study, 92 patients with essential hypertension were randomized to treatment with a TFC of perindopril/indapamide/amlodipine at different doses or a triple free combination therapy (FCT) including ACEI/diuretic/CCB. Office blood pressure (BP) measurement, 24 h-ambulatory BP monitoring and echocardiography were performed at baseline and during a 14-month follow-up. The BP variability (BPV) over 24 h was calculated as ± standard deviation of the daytime systolic BP. Differences between office and monitored BP and LVMI were evaluated by ANOVA for repeated measures. RESULTS A significant BP-lowering effect was observed for both treatments. At follow-up, BPV was reduced in both the treatment groups vs. the baseline (14.0±1.5 vs. 17.0±1.8 and 16.2±2.1 vs. 17.6±2.3, respectively), but it was lower in the TFC vs. the FCT group (14.0±1.5 vs. 16.1±2.2, P < 0.05). LVMI was lower in both the treatment groups, but the change was greater for TFC vs. FCT (-8.3±4.9% vs. -2.0 ±2.1%, P < 0.0001). Left ventricular hypertrophy (LVH) regression was greater in the TFC vs. the FCT group (43.5% vs. 30.4%, P < 0.05). CONCLUSIONS Independently of BP values achieved, the antihypertensive TFC therapy was more effective than FCT in LVMI reduction and LVH regression, possibly related to drugs' intrinsic properties and to BPV modulation.
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A randomized, controlled study evaluating effects of amlodipine addition to chelators to reduce iron loading in patients with thalassemia major.
Eghbali, A, Kazemi, H, Taherahmadi, H, Ghandi, Y, Rafiei, M, Bagheri, B
European journal of haematology. 2017;(6):577-581
Abstract
AIM: Cardiomyopathy due to iron overload can be fatal in patients with thalassemia major. Calcium channel blockers seem to be effective to reduce iron loading. Our goal was to study effects of amlodipine addition to chelators on iron loading in patients with thalassemia major. METHODS This randomized, controlled, and single-center trial was performed on 56 patients with thalassemia major. Patients were randomized 1:1 to combined group (iron chelator plus amlodipine) or control group (iron chelator) for 1 year. Iron content was measured by magnetic resonance imaging; heart T2*, and liver T2*. Serum ferritin was also measured. RESULTS After 12 months of treatment, myocardial T2* values had significant improvement in combined group (21.9 ± 8.0 ms to 24.5 ± 7.6 ms; P < .05); Difference between two groups was significant (P = .02). Combined treatment had no effect on hepatic T2* value (9.6 ± 2.8 ms to 9.5 ± 3.6 ms); difference between two groups was not significant (P = .2). In addition, a significant reduction was seen in serum ferritin levels in two groups. Mild gastrointestinal upset was the most common untoward effect. CONCLUSION Addition of amlodipine to iron chelators has beneficial effects for reduction of iron loading in patients with thalassemia major. This combination therapy seems safe.
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Adding Hydrochlorothiazide to Olmesartan/Amlodipine Increases Efficacy in Patients With Inadequate Blood Pressure Control on Dual-Combination Therapy.
Rump, LC, Ammentorp, B, Laeis, P, Scholze, J
Journal of clinical hypertension (Greenwich, Conn.). 2016;(1):60-9
Abstract
This randomized, parallel-group study in patients inadequately controlled on olmesartan medoxomil/amlodipine (OLM/AML) 40/10 mg assessed the effects of adding hydrochlorothiazide (HCTZ) 12.5 mg and 25 mg, using seated blood pressure (SeBP) measurements and ambulatory blood pressure (BP) monitoring. Enrolled patients were screened and tapered off of therapy if required. All patients received OLM/AML 40/10 mg and those with mean seated BP (SeBP) ≥140/90 mm Hg after 8 weeks (n=808) were randomized (1:1:1) to continue with OLM/AML 40/10 mg or receive OLM/AML/HCTZ 40/10/12.5 or 40/10/25 mg for a further 8 weeks. The primary endpoint was the change in seated diastolic BP (SeDBP) from the start to the end of the randomized treatment period. The addition of HCTZ 25 mg significantly reduced SeDBP (-2.8 mm Hg; P<.0001), lowered seated systolic BP (SeSBP) and ambulatory DBP and SBP, and improved BP goal rates. In patients uncontrolled on OLM/AML 40/10 mg, adding HCTZ led to further BP reductions, particularly in ambulatory BP.
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Incremental Blood Pressure-Lowering Effect of Titrating Amlodipine for the Treatment of Hypertension in Patients Including Those Aged ≥55 Years.
Jeffers, BW, Bhambri, R, Robbins, J
American journal of therapeutics. 2015;(4):278-87
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Abstract
Small reductions in blood pressure reduce the risk of cardiovascular events. Here, we report 2 post hoc pooled analyses assessing the antihypertensive effect of amlodipine in patients who had not responded to 5 mg and were uptitrated to 10 mg. The first analysis assessed subgroups of patients aged either younger than 55 years or 55 years or older and the second analysis pooled all patients irrespective of age. Of 706 patients in the age-related analysis, a statistically significant decrease in blood pressure from baseline was observed {for younger than 55 years [N = 253]: systolic blood pressure = -12.8 [standard error (SE) = 0.90] mm Hg, diastolic blood pressure = -8.0 [SE = 0.55] mm Hg; for 55 years or older [N = 453]: systolic blood pressure = -12.1 [SE = 0.66] mm Hg, diastolic blood pressure = -6.7 [SE = 0.39] mm Hg; all P < 0.0001}. In total, 45.8% and 39.3% of patients aged younger than 55 and 55 years or older, respectively, achieved their blood pressure goals. Adverse events were experienced by 62 (24.5%) patients aged younger than 55 years and 136 (30.0%) patients aged 55 years or older. Similar efficacy and safety results were seen in the all patient pooled analysis. Titration of amlodipine from 5 mg to 10 mg significantly decreased blood pressure in older hypertensive patients, which is clinically relevant because increased age is associated with hypertension and cardiovascular events.
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A Randomized, Multicenter, Double-blind, Placebo-controlled, 3 × 3 Factorial Design, Phase II Study to Evaluate the Efficacy and Safety of the Combination of Fimasartan/Amlodipine in Patients With Essential Hypertension.
Lee, HY, Kim, YJ, Ahn, T, Youn, HJ, Chull Chae, S, Seog Seo, H, Kim, KS, Rhee, MY, Choi, DJ, Kim, JJ, et al
Clinical therapeutics. 2015;(11):2581-2596.e3
Abstract
PURPOSE The objective of this study was to evaluate the efficacy and safety of a fimasartan/amlodipine combination in patients with hypertension and to determine the optimal composition for a future single-pill combination formulation. METHODS This Phase II study was conducted by using a randomized, multicenter, double-blind, placebo-controlled, 3 × 3 factorial design. After a 2-week placebo run-in period, eligible hypertensive patients (with a sitting diastolic blood pressure [SiDBP] between 90 and 114 mm Hg) were randomized to treatment. They received single or combined administration of fimasartan at 3 doses (0, 30, and 60 mg) and amlodipine at 3 doses (0, 5, and 10 mg) for 8 weeks. The primary efficacy end point was the change in SiDBP from baseline and at week 8; secondary end points included the change in SiDBP from baseline and at week 4 and the changes in sitting systolic blood pressure from baseline and at weeks 4 and 8. Treatment-emergent adverse events (AEs) were also assessed. FINDINGS 420 Korean patients with mild to moderate hypertension were randomly allocated to the 9 groups. Mean (SD) SiDBP changes in each group after 8 weeks were as follows: placebo, -6.0 (8.5) mm Hg; amlodipine 5 mg, -10.6 (9.2) mm Hg; amlodipine 10 mg, -15.9 (7.2) mm Hg; fimasartan 30 mg, -10.1 (9.1) mm Hg; fimasartan 60 mg, -13.0 (10.0) mm Hg; fimasartan 30 mg/amlodipine 5 mg, -16.2 (8.5) mm Hg; fimasartan 30 mg/amlodipine 10 mg, -19.5 (7.5) mm Hg; fimasartan 60 mg/amlodipine 5 mg, -16.6 (6.9) mm Hg; and fimasartan 60 mg/amlodipine 10 mg, -21.5 (8.3) mm Hg. All treatment groups produced significantly greater reductions in blood pressure compared with the placebo group. In addition, all combination treatment groups had superior reductions in blood pressure compared with the monotherapy groups. In the combination treatment groups, doubling fimasartan dose in the given dose of amlodipine did not show further BP reduction, whereas doubling amlodipine dose showed significantly further BP reduction in the given dose of fimasartan. During the study period, 75 (17.9%) of 419 patients experienced 110 AEs. Ninety-five AEs were mild, 9 were moderate, and 6 were severe in intensity. Eight patients discontinued the study due to AEs. There was no significant difference in incidence of AEs among groups (P = 0.0884). The most common AE was headache (12 patients [2.9%]), followed by dizziness (11 patients [2.6%]) and elevated blood creatine phosphokinase levels (6 patients [1.4%]). IMPLICATIONS Fimasartan combined with amlodipine produced superior blood pressure reductions and low levels of AEs compared with either monotherapy. Therefore, a single-pill combination with fimasartan 60 mg/amlodipine 10 mg will be developed. ClinicalTrials.gov: NCT01518998.
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[Cardio-Nephroprotection--the Most Important Goal of Antihypertensive Therapy in Patients With Type 2 Diabetes].
Statsenko, ME, Derevyanchenko, MV
Kardiologiia. 2015;(8):43-8
Abstract
AIM: to study the opportunities for cardio and nephroprotection by 6-month combined antihypertensive therapy with lisinopril and amlodipine in hypertensive patients with diabetes mellitus (DM) type 2. MATERIALS AND METHODS 30 patients with arterial hypertension (AH) stage II-III, chronic kidney disease (CKD) stages 2-3 and type 2 DM were included in to research. We evaluated the results of the physical examination, blood pressure monitoring (ABPM), structural and functional state of the heart and kidneys. Combined analysis the risk of progression of CKD and cardiovascular complications (CVC) depending on the glomerular filtration rate (GFR) and albuminuria (AU) was performed. We also studied carbohydrate and lipid metabolism and estimated the severity of insulin resistance (IR). RESULTS Against the background of long-term therapy by Equator 100% of patients had achieved target BP values. The circadian BP profile was significantly improved. There was a significant decrease in the index of left ventricular mass by 8.0%, a decline of PU by 58% and AU by 43.6%, respectively. There was the redistribution of patients to assess the combined risk of CKD progression and CVC: 50% of patients in the group crossed a moderate risk by reducing the percentage of patients at high and very high risk of 36.7% and 13.4%, respectively (p < 0.001), as well as significant improvement in metabolic parameters and reduction in IR. A statistically significant correlation between IR and condition of the heart and kidney was determined. CONCLUSION Long-term combined therapy with lisinopril and amlodipine fully meets the modern requirements for antihypertensive therapy--it leads to a significant reduction in the risk of progression of CKD and development of the CVC and is metabolically neutral. The decrease in the combined risk of CKD progression and development CVC was associated with cardio and nephroprotective action of the Equator, as well as with a reduction in the negative impact of IR in patients with AH and type 2 DM.
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Different aspects of sartan + calcium antagonist association compared to the single therapy on inflammation and metabolic parameters in hypertensive patients.
Derosa, G, Cicero, AF, Carbone, A, Querci, F, Fogari, E, D'Angelo, A, Maffioli, P
Inflammation. 2014;(1):154-62
Abstract
This study aims to evaluate the effects of an angiotensin receptor blocker (ARB)/calcium channel blocker combination on blood pressure control, lipid profile, insulin sensitivity, and inflammation markers. We randomized 276 hypertensive patients to olmesartan 20 mg, amlodipine 10 mg, or a single pill containing an olmesartan/amlodipine combination 20/5 mg for 12 months. We evaluated the following: body weight, systolic and diastolic blood pressure, fasting plasma glucose, fasting plasma insulin (FPI), M value, lipid profile, adiponectin (ADN), high sensitivity C-reactive protein (Hs-CRP), monocyte chemoattractant protein-1 (MCP-1), and macrophage migration inhibitory factor-1β (MIP-1β). Olmesartan/amlodipine combination better reduced blood pressure, FPI, homeostasis model assessment index, and increased M value and ADN compared to olmesartan and amlodipine monotherapies. Olmesartan/amlodipine significantly decreased Hs-CRP, MCP-1, and MIP-1β. In this multicenter, randomized, double-blind, clinical study, ARB/calcium antagonist combination resulted to be more effective than single monotherapies in reducing blood pressure, in improving insulin sensitivity, and in reducing inflammation parameters in patients with stage I essential hypertension.
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Slovak trial on cardiovascular risk reduction following national guidelines with CaDUET® (the STRONG DUET study).
Fedacko, J, Pella, D, Jarcuska, P, Sabol, F, Kmec, J, Lopuchovsky, T, Merkovska, L, Jedlickova, L, Janicko, M, Sajty, M
Advances in therapy. 2013;(1):60-70
Abstract
INTRODUCTION The efficacy and safety of single-pill amlodipine/atorvastatin for reducing blood pressure (BP), low-density lipoprotein cholesterol (LDLC), and predicted 10-year cardiovascular (CV) risk have been demonstrated in low CV risk countries. The Slovak Trial on Cardiovascular Risk Reduction Following National Guidelines with CaDUET® (amlodipine besylate/atorvastatin calcium; Pfizer, Morrisville, PA, USA; STRONG DUET) study evaluated its clinical utility in Slovakia, one of the highest CV risk regions in Europe. METHODS This was a two-phase study involving 100 outpatient cardiologist and internist departments in Slovakia. Phase 1 assessed BP control and CV risk profiles in adults with treated hypertension, and phase 2 was an open-label, multicenter, observational study. In the phase 2 study, patients with treated but uncontrolled hypertension and three or more coronary heart disease risk factors received single-pill amlodipine/atorvastatin (5/10 or 10/10 mg) for 12 weeks. Major outcomes were the percentage of patients achieving target BP (≤140/90 mmHg) and/or LDL-C (≤3 mmol/L) and reductions in predicted 10-year CV risk. RESULTS Of the 4,672 phase 1 patients, 80.8% had uncontrolled hypertension and 61.4% had dyslipidemia. Of the 1,406 phase 2 patients, 90.3% of patients achieved target BP at week 12, 66.3% achieved target LDL-C, and 60.7% achieved both. The mean 10-year CV risk was reduced by 49% (P < 0.0001); treatment was well-tolerated and safe. CONCLUSION Single-pill amlodipine/atorvastatin was associated with significant improvements in BP, LDL-C target attainment, and 10-year CV risk in patients with uncontrolled hypertension in Slovakia. The treatment was well-tolerated and safe. Use of single-pill amlodipine/atorvastatin in high CV-risk countries could lead to significant improvements in CV risk management.