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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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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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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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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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The Interaction of a Diabetes Gene Risk Score With 3 Different Antihypertensive Medications for Incident Glucose-level Elevation.
Barzilay, JI, Lai, D, Davis, BR, Pressel, S, Previn, HE, Arnett, DK
American journal of hypertension. 2019;(4):343-349
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BACKGROUND Elevations of fasting glucose (FG) levels are frequently encountered in people treated with thiazide diuretics. The risk is lower in people treated with ACE inhibitors (ACEi). To determine if genetic factors play a role in FG elevation, we examined the interaction of a diabetes gene risk score (GRS) with the use of 3 different antihypertensive medications. METHODS We examined 376 nondiabetic hypertensive individuals with baseline FG <100 mg/dl who were genotyped for 24 genes associated with risk of elevated glucose levels. All participants had ≥1 follow-up FG level over 6 years of follow-up. Participants were randomized to treatment with a thiazide-like diuretic (chlorthalidone), a calcium channel blocker (CCB; amlodipine), or an ACEi (lisinopril). Outcomes were an FG increase of ≥13 or ≥27 mg/dl, the upper 75% and 90% FG increase in the parent cohort from which the present cohort was obtained. Odds ratios were adjusted for factors that increase FG levels. RESULTS For every 1 allele increase in GRS, the adjusted odds ratios (ORs) were 1.06 (95% confidence interval (CI): 0.99, 1.14; P = 0.06) and 1.09 (95% CI: 0.99, 1.20; P = 0.08). When results were examined by randomized medications, participants randomized to amlodipine had statistically significant odds for either outcome (OR: 1.23; 95% CI: 1.03, 1.48; P = 0.01 and OR: 1.31; 95% CI: 1.06, 1.62; P = 0.01). No such risk increase was found in participants randomized to the other 2 medications. CONCLUSIONS A diabetes GRS predicts FG elevation in people treated with a CCB, but not with an ACEi or diuretic. These findings require confirmation. CLINICAL TRIALS REGISTRATION Trial number NCT00000542.
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[Antihypertensive Effect of Switching to a Fixed Perindopril/Amlodipine Combination in Patients Ineffectively Treated by Free Sartan-Containing Combinations. Results of the AVANGARD Study].
Glezer, MG
Kardiologiia. 2019;(10):31-38
Abstract
UNLABELLED Finding the best options for combined antihypertensive therapy is one of the main tasks to be solved for achieving target blood pressure (BP) and, accordingly, reduction of the risk of complications in patients with arterial hypertension (AH).Purpose of this study was to evaluate the effectiveness of the perindopril arginine/amlodipine fixed combination in patients with 1-2 degree hypertension not achieving BP control on previous therapy with sartan-containing free combinations. MATERIALS AND METHODS In the multicenter open uncontrolled observational program AVANGARD 203 doctors in 53 cities of the Russian Federation included 658 patients who had not achieved target BP on therapy with two drugs, one of which was sartan (sartan with diuretic, calcium antagonist, β-blocker, or moxonidine in 49%, 33%, 17%, and 1% of cases, respectively). This therapy was replaced with a fixed combination of perindopril arginine/amlodipine. Duration of observation was 3 months. RESULTS On therapy with perindopril arginine/amlodipine, BP decreased 159.9±8.5/92.1±7.4 to 125.8±7.1/77.4±5.5 mm Hg. Target BP <140/90 mm Hg was achieved in 93.5% of patients (office measurement); target BP <135/85 mm Hg - in 83.5% of patients (home measurement). Mean 24-hour BP variability decreased from 4.4±2.9/3.0±2.0 to 3.0±2.2/2.2±1.7 mm Hg (p<0.01). Number of patients complaining of headache decreased by 2.9 times, dizziness - by 2.8 times, fatigue - by 2.3 times, irritability - by 3.0 times, sleep disturbances - by 2.3 times, dyspnea - by 3.8 times, palpitations - by 2.7 times, angina pectoris attacks - by 4.6 times. Dose of perindopril arginine/amlodipine was 10/5 mg in 36.6%, and 10/10 mg in 28.3% of cases, respectively. Number ofparticipants who dropped out ofthe study prematurely was 11 (1.6%) (1 because of adverse event). Adverse events were observed in 4 more patients (2 [0.14%] - edema of lower extremities, and 2 [0.14%] -cough), but they did not require the withdrawal of therapy. CONCLUSION In case of ineffective combination therapy containing sartans, transfer of patients to a fixed combination of perindopril and amlodipine should be considered.
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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.