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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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[Effects of changing the appearance of medications in safety and adherence in chronic patients over 65 years of age in primary care. CAMBIMED Study].
Arancón-Monge, JM, de Castro-Cuenca, A, Serrano-Vázquez, Á, Campos-Díaz, L, Rodríguez Barrientos, R, Del Cura-González, I, , , ,
Atencion primaria. 2020;(2):77-85
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Abstract
OBJECTIVE To study whether the changes in bioequivalent drugs with different appearances are associated with an increase in lack of adherence and medication use errors, in patients >65years old treated with antihypertensive and lipid-lowering medications. DESIGN Observational longitudinal prospective cohort study with a one-year follow-up period between 1 January 2013 and 31 December 2014. LOCATION Primary Healthcare Centres in the Community of Madrid. PARTICIPANTS Patients ≥65years-old with a diagnosis of hypertension and/or dyslipidaemia receiving treatment with Enalapril and/or Amlodipine and/or Simvastatin. MAIN MEASUREMENTS Variables collected during a Primary Care consultation by means of a personal interview were: sociodemographic (age, gender, level of education), clinical variables, adherence (Morisky-Green test and direct counting), medication errors (number and type), medication changes and number, analytical (total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides) and combined variable (error and/or adherence). There were 1 baseline and 4 quarterly visits. RESULTS The study included 274 patients with a mean age 72 (6.6) years, of whom 47.8% were female. Some medication changes were observed in 134 patients (48.9%), with a median of 3 (IQR 1-5) and a maximum of 11 changes. The risk of presenting with a medication use error or decreased adherence was increased in patients exposed to changes in all visits with RR 1.14 (1.16-1.69) at one year of follow-up. The most frequent error was the loss of dose. For each change in medication, the probability of a combined event increases by 41%. CONCLUSIONS The changes made in bioequivalent drugs with different appearance could increase the number of medication use errors and decrease the adherence. More studies should be carried out to assess how much this affects the control of the disease. The intervention section is not considered because it is an observational study.
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Comparison of Blood Pressure Variability Between Losartan and Amlodipine in Essential Hypertension (COMPAS-BPV).
Lee, JW, Choi, E, Son, JW, Youn, YJ, Ahn, SG, Ahn, MS, Kim, JY, Lee, SH, Yoon, J, Ryu, DR, et al
American journal of hypertension. 2020;(8):748-755
Abstract
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.
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Low Baseline High-Sensitive C-Reactive Protein is Associated with Coronary Atherosclerosis Regression: Insights from the MILLION Study.
Sakata, K, Gamou, T, Tada, H, Hayashi, K, Ino, H, Yamagishi, M, , , ,
Journal of atherosclerosis and thrombosis. 2019;(5):442-451
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Abstract
AIM: The prospective, randomized, multicenter Myocardial Ischemia Treated with Percutaneous Coronary Intervention and Plaque Regression by Lipid Lowering & Blood Pressure Controlling assessed by Intravascular Ultrasonography (MILLION) study demonstrated that combined treatment with atorvastatin and amlodipine enhanced coronary artery plaque regression. Although the baseline high-sensitive C-reactive protein (hs-CRP) reportedly plays an important role in atherogenesis, few data exist regarding the relationship between hs-CRP and plaque regression in patients receiving a combined atorvastatin and amlodipine therapy. METHODS A total of 68 patients (male, 55; mean age, 64.2 years) with baseline and follow-up 3-dimensional intravascular ultrasound examinations in the MILLION study were stratified by baseline hs-CRP level quartiles. The serial measurements of lipid, blood pressure, and percentage changes in the plaque volume were compared between the groups, and the factors associated with the percentage change in the plaque volume were assessed. RESULTS There were no significant between-group differences in the extent of change in low-density lipoprotein cholesterol (LDL-C) or systolic and diastolic blood pressure after 18-24 months of treatment. The percentage change in the plaque volume showed a linear association with the baseline hs-CRP (p for trend <0.05); however, there was no correlation with changes in LDL-C or systolic and diastolic blood pressure. In the multiple regression analysis, the baseline hs-CRP level was independently associated with the percentage change in the plaque volume (β=0.29, p=0.022). CONCLUSIONS Coronary plaque regression was associated with the baseline hs-CRP level in patients treated with a combined lipid- and blood pressure-lowering therapy.
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Influence of Amlodipine on Haemostatic Measurements during Clopidogrel Treatment in Patients with Coronary Artery Disease.
Koh, JS, Park, Y, Ahn, JH, Kang, MG, Kim, KH, Bae, JS, Park, HW, Jang, JY, Park, JR, Hwang, SJ, et al
Thrombosis and haemostasis. 2019;(2):264-273
Abstract
Amlodipine has a potential to reduce clopidogrel bioactivation through the cytochrome P450 3A4 enzyme in vivo, but the clinical impact of this interaction remains controversial. This randomized, open-label, two-period, crossover study was performed to evaluate the influence of amlodipine on the haemostatic profiles of high-risk patients during clopidogrel treatment. We recruited 40 Asian patients (Male/Female: n = 36/4) receiving clopidogrel (75 mg/day), aspirin (100 mg/day) and rosuvastatin for at least 6 months following percutaneous coronary intervention. Patients were randomly assigned to receive either 5 mg daily amlodipine or not for 2 weeks, and then were crossed over to the other treatment for 2 weeks. Haemostatic measurements were conducted with the VerifyNow assay and thromboelastography (TEG). Primary endpoint was P2Y12 Reaction Units (PRU) during on- versus off-amlodipine treatment. The on-amlodipine strategy showed higher level of PRU compared with the off-amlodipine strategy (176.8 ± 75.4 vs. 150.7 ± 65.5 PRU; ∆mean: 26.1 PRU; ∆95% confidence interval [CI]: 4.5-47.7 PRU; p = 0.019). Platelet-fibrin clot strength measured by TEG was lower during on- versus off-amlodipine treatment (7,712 ± 1,889 vs. 8,559 ± 2,174 dyne/cm2; ∆mean: -847 dyne/cm2; ∆95% CI: -1,632 to -62 dyne/cm2; p = 0.035). After amlodipine discontinuation, 27 patients (67.5%) showed a decrease in PRU, which was associated with 'PRU ≥ 160 on-amlodipine' in multivariate analysis (odds ratio: 62.014; 95% CI: 2.302-1670.328; p = 0.014). In conclusion, amlodipine increases platelet reactivity and decreases platelet-fibrin clot strength during clopidogrel treatment. In addition, the effect of amlodipine discontinuation on clopidogrel responsiveness is associated with on-amlodipine platelet reactivity.
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Comparative effects of 2.5mg levamlodipine and 5mg amlodipine on vascular endothelial function and atherosclerosis.
Lu, Y, Yin, J, Wu, X, Fan, Y, Liu, F
Pakistan journal of pharmaceutical sciences. 2019;(5(Special)):2433-2436
Abstract
This study was designed to compare the efficacy of two different racemic antihypertensive drugs on elderly patients with hypertension and their effects on vascular endothelial function and atherosclerosis. A total of 84 elderly hypertensive patients were randomly divided into control and treatment group with 42 patients in each group. The control group was treated with 2.5mg levamlodipine while the treatment group was given 5mg amlodipine. Total effective rate of the treatment group was 90.5%, higher than the control group, that was 71.4% (P<0.05). The time for recovery of related indicators like blood pressure, the total duration of medication were significantly (P<0.05) shorter in the treatment group. Only 1 case of adverse drug reaction was found in the treatment group while 6 cases in control group. Compared to the control group, the treatment group had massive improvement in fingertip pulse volume, flow-mediated dilation of the brachial arteries and endothelin-1 level, carotid intima-media thickness, plaque length & thickness, and blood pressure after the administration. The rate of satisfaction with the in treatment group was 95.3%, higher than that the control group, which was 78.6%. The study concluded that in elderly patients with hypertension, the treatment with 5mg amlodipine enhanced curative effect, fully improved endothelial function & arteriosclerosis and reduced adverse reactions thereby shortening treatment time.
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Amlodipine alters hemorheological parameters: Increased efficacy at the cost of edema?
Ravindra, RP, Arunkumar, S, Puniyani, RR, Padgaonkar, K, Vadivelu, R, Sharma, R, Panicker, G, Lokhandwala, Y
Indian heart journal. 2019;(1):32-38
Abstract
BACKGROUND Despite several decades of use of calcium channel blockers, the side effect of edema persists as a class effect, and its mechanism is unresolved. Amlodipine has effects on hemorheology (HR), and its hemodilutory property may partly contribute to its antihypertensive action. This aspect is not well studied, and the literature is sparse in this regard. OBJECTIVE This experiment was planned to determine effect of a single-dose administration of amlodipine on HR parameters in normal human volunteers. METHODS AND RESULTS Amlodipine (5 mg) or S (-) amlodipine (2.5 mg) was administered to 27 normal human volunteers. Whole-blood viscosity (WBV) at different shear rates, plasma viscosity (PV), red cell rigidity (RCR), red cell aggregation (RCA), hematocrit (Hct), plasma hemoglobin, along with plasma drug concentration were determined at time intervals, t = 0, 4, 8, 12, and 24 h. Statistically significant reductions were observed at tmax = 4 h in WBV at shear rates of 0.512 s-1 (p < 0.005), WBV at shear rates of 5.26 s-1 (p < 0.01), PV (p < 0.05), and Hct (p < 0.01). At t = 8 h, as drug concentration reduced, some of the changes persisted and later slowly decreased with the decreasing drug concentration till t = 24 h. Red blood cell-related parameters such as RCA and RCR remained unaltered. WBV values at all shear rates, when corrected for Hct = 0.45, did not show deviation from their original values at any time. CONCLUSIONS Amlodipine causes a reduction in Hct and blood viscosity, along with hemodilution. These effects persist as long as the drug remains in plasma. Edema resulting from chronic dosing may be explained by the aforementioned effects. It is possible that antihypertensive action of the drug may be due to a combination of vasodilatation and an improvement in the HR properties.
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Pharmacokinetic Interaction Among Telmisartan, Amlodipine, and Hydrochlorothiazide After a Single Oral Administration in Healthy Male Subjects.
Moon, SJ, Jeon, JY, Yu, KS, Kim, MG
Clinical therapeutics. 2019;(11):2273-2282
Abstract
PURPOSE Hypertension is a major risk factor for cardiovascular diseases, necessitating hypertension control. Antihypertensive drugs are more potent when administered in combinations of 2 or 3 different classes of drugs. One such therapy includes a combination of an angiotensin receptor blocker, a calcium channel blocker, and a diuretic. The objective of this study was to evaluate the pharmacokinetic interaction among telmisartan, amlodipine, and hydrochlorothiazide. METHODS A randomized, open-label, 3-period, 6-sequence, 3-treatment, single-dose crossover study was conducted in healthy male subjects. Subjects were randomly assigned to 1 of 6 sequences and one of the following treatments was administered in each period: treatment A, co-administration of one tablet of telmisartan 80 mg and one tablet of amlodipine 10 mg; treatment B, one tablet of hydrochlorothiazide 25 mg alone; and treatment C, co-administration of all 3 investigational products. Serial blood samples were collected up to 144 hours postdose. Plasma drug concentrations were measured by using LC/MS-MS. Pharmacokinetic parameters, including Cmax and AUC0-last, were determined by using noncompartmental analysis. The geometric least squares mean ratios and associated 90% CIs of log-transformed Cmax and AUC0-last for separate administration or co-administration were calculated to evaluate pharmacokinetic interactions. FINDINGS Twenty-seven subjects completed the study. The geometric least squares mean ratios and 90% CIs of Cmax and AUC0-last were 1.02 (0.85-1.21) and 1.04 (0.97-1.13) for telmisartan; 1.00 (0.95-1.04) and 0.95 (0.91-0.99) for amlodipine; and 0.88 (0.82-0.96) and 0.86 (0.82-0.90) for hydrochlorothiazide, respectively. No serious adverse events were recorded, and all reported adverse events were of mild intensity. IMPLICATIONS The pharmacokinetic parameters of telmisartan, amlodipine, and hydrochlorothiazide when administered separately or co-administered were compared, and all the parameters met the criteria for pharmacokinetic equivalence. Combination therapy of these 3 drugs had no significant impact on the pharmacokinetic parameters of each drug. (ClinicalTrials.gov Identifier: NCT03889145).
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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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Randomized trial of an increased dose of calcium channel blocker or angiotensin II type 1 receptor blocker as an add-on intensive depressor therapy in type 2 diabetes mellitus patients with uncontrolled essential hypertension: the ACADEMIE Study.
Imaizumi, S, Shiga, Y, Ogawa, M, Sako, H, Nagata, Y, Matsunaga, A, Shirotani, T, Hoshino, F, Yahiro, E, Uehara, Y, et al
Heart and vessels. 2019;(4):698-710
Abstract
There is a lack of data on how to treat hypertensive patients with diabetes when treatment with medium doses of calcium channel blocker and angiotensin II type 1 receptor blocker (ARB) is insufficient to achieve the target blood pressure (BP). A total of 121 participants with type 2 diabetes and uncontrolled essential hypertension, who were receiving medium doses of amlodipine (5 mg/day) and ARB, were enrolled. Participants were randomized to receive either a high dose of amlodipine (10 mg/day) plus a medium dose of ARB (high-AML) or a medium dose of amlodipine (5 mg/day) plus a high dose of ARB (high-ARB). The depressor effects of these two regimens were monitored using a telemonitoring home BP-measuring system. Fifty-four patients were excluded after an observation period, and the remaining 67 eligible participants were randomized into the two groups; 42 which had a record of their home BP for analysis. The change in morning home systolic and diastolic BP was greater in the high-AML than in the high-ARB (systolic BP; - 7.9 mmHg vs. + 2.7 mmHg; p = 0.0002, diastolic BP; - 3.9 mmHg vs. + 0.6 mmHg; p = 0.0007). In addition, the home systolic and diastolic BP before going to bed and office systolic BP were significantly reduced from week 0 only in the high-AML. An increased dose of amlodipine, but not ARB, reduced home morning BP in hypertensive patients with type 2 diabetes who were already receiving combination therapy with medium doses of amlodipine and ARB.