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Journal of Clinical Hypertension... Sep 2023Hypertension is the leading cause of death worldwide, affecting 1.4 billion people. Treatment options include the widely used calcium channel blockers, among which... (Review)
Review
Hypertension is the leading cause of death worldwide, affecting 1.4 billion people. Treatment options include the widely used calcium channel blockers, among which amlodipine, a dihydropyridine, has unique characteristics that distinguish it from other drugs within this class. This review aims to provide an updated overview of the evidence supporting the use of amlodipine over the past 30 years and highlights its cardiovascular benefits in current hypertension management. Amlodipine has low renal clearance (7 mL/min/mg) and long half-life (35-50 h) and duration of action, which allows it to sustain its anti-hypertensive effect for more than 24 h following a single dose. Additionally, blood pressure (BP) control is maintained even when a dose has been missed, providing continuous protection in case of incidental noncompliance. It has proven to reduce BP variability and successfully lower BP. Amlodipine also controls BP in patients with a systolic/diastolic BP of 130/80 mm Hg or higher, diabetes, or chronic kidney disease without worsening glycemic or kidney function. Additionally, amlodipine is a wise choice for older adults due to its ability to control BP and protect against stroke and myocardial infarction. Side effects of amlodipine include edema, palpitations, dizziness, and flushing, which are more common with the higher dose of 10 mg. Amlodipine is cost effective and predicted to be cost saving when compared with usual care.
Topics: Humans; Aged; Amlodipine; Hypertension; Antihypertensive Agents; Calcium Channel Blockers; Blood Pressure
PubMed: 37551050
DOI: 10.1111/jch.14709 -
Clinical Cardiology Aug 2023This study aimed to evaluate the efficacy of single-pill combination (SPC) antihypertensive drugs in patients with uncontrolled essential hypertension. Through Searching... (Meta-Analysis)
Meta-Analysis Review
This study aimed to evaluate the efficacy of single-pill combination (SPC) antihypertensive drugs in patients with uncontrolled essential hypertension. Through Searching Pubmed, EMBASE, the Cochrane Library, and Web of Science collected only randomized controlled trials on the efficacy of single-pill combination antihypertensive drugs in people with uncontrolled essential hypertension. The search period is from the establishment of the database to July 2022. The methodological quality of the included studies was assessed using the Cochrane Risk of Bias Assessment, and statistical analyses were performed using Review Manage 5.3 and Stata 15.1 software. This review ultimately included 32 references involving 16 273 patients with uncontrolled essential hypertension. The results of the network meta-analysis showed that a total of 11 single-pill combination antihypertensive drugs were included, namely: Amlodipine/valsartan, Telmisartan/amlodipine, Losartan/HCTZ, Candesartan/HCTZ, Amlodipine/benazepril, Telmisartan/HCTZ, Valsartan/HCTZ, Irbesartan/amlodipine, Amlodipine/losartan, Irbesartan/HCTZ, and Perindopril/amlodipine. According to SUCRA, Irbesartan/amlodipine may rank first in reducing systolic blood pressure (SUCRA: 92.2%); Amlodipine/losartan may rank first in reducing diastolic blood pressure (SUCRA: 95.1%); Telmisartan/amlodipine may rank first in blood pressure control rates (SUCRA: 83.5%); Amlodipine/losartan probably ranks first in diastolic response rate (SUCRA: 84.5%). Based on Ranking Plot of the Network, we can conclude that single-pill combination antihypertensive drugs are superior to monotherapy, and ARB/CCB combination has better advantages than other SPC in terms of systolic blood pressure, diastolic blood pressure, blood pressure control rate, and diastolic response rate. However, due to the small number of some drug studies, the lack of relevant studies has led to not being included in this study, which may impact the results, and readers should interpret the results with caution.
Topics: Humans; Antihypertensive Agents; Losartan; Hypertension; Telmisartan; Irbesartan; Angiotensin Receptor Antagonists; Network Meta-Analysis; Hydrochlorothiazide; Valine; Drug Therapy, Combination; Angiotensin-Converting Enzyme Inhibitors; Amlodipine; Valsartan; Tetrazoles; Blood Pressure; Essential Hypertension
PubMed: 37432701
DOI: 10.1002/clc.24082 -
The Lancet. Neurology Nov 2023Hypertension is the leading risk factor for cerebral small vessel disease. We aimed to determine whether antihypertensive drug classes differentially affect... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of blood pressure-lowering agents on microvascular function in people with small vessel diseases (TREAT-SVDs): a multicentre, open-label, randomised, crossover trial.
BACKGROUND
Hypertension is the leading risk factor for cerebral small vessel disease. We aimed to determine whether antihypertensive drug classes differentially affect microvascular function in people with small vessel disease.
METHODS
We did a multicentre, open-label, randomised crossover trial with blinded endpoint assessment at five specialist centres in Europe. We included participants aged 18 years or older with symptomatic sporadic small vessel disease or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and an indication for antihypertensive treatment. Participants were randomly assigned (1:1:1) to one of three sequences of antihypertensive treatment using a computer-generated multiblock randomisation, stratified by study site and patient group. A 2-week washout period was followed by three 4-week periods of oral monotherapy with amlodipine, losartan, or atenolol at approved doses. The primary endpoint was change in cerebrovascular reactivity (CVR) determined by blood oxygen level-dependent MRI response to hypercapnic challenge in normal-appearing white matter from the end of washout to the end of each treatment period. Efficacy analyses were done by intention-to-treat principles in all randomly assigned participants who had at least one valid assessment for the primary endpoint, and analyses were done separately for participants with sporadic small vessel disease and CADASIL. This trial is registered at ClinicalTrials.gov, NCT03082014, and EudraCT, 2016-002920-10, and is terminated.
FINDINGS
Between Feb 22, 2018, and April 28, 2022, 75 participants with sporadic small vessel disease (mean age 64·9 years [SD 9·9]) and 26 with CADASIL (53·1 years [7·0]) were enrolled and randomly assigned to treatment. 79 participants (62 with sporadic small vessel disease and 17 with CADASIL) entered the primary efficacy analysis. Change in CVR did not differ between study drugs in participants with sporadic small vessel disease (mean change in CVR 1·8 × 10%/mm Hg [SE 20·1; 95% CI -37·6 to 41·2] for amlodipine; 16·7 × 10%/mm Hg [20·0; -22·3 to 55·8] for losartan; -7·1 × 10%/mm Hg [19·6; -45·5 to 31·1] for atenolol; p=0·39) but did differ in patients with CADASIL (15·7 × 10%/mm Hg [SE 27·5; 95% CI -38·3 to 69·7] for amlodipine; 19·4 × 10%/mm Hg [27·9; -35·3 to 74·2] for losartan; -23·9 × 10%/mm Hg [27·5; -77·7 to 30·0] for atenolol; p=0·019). In patients with CADASIL, pairwise comparisons showed that CVR improved with amlodipine compared with atenolol (-39·6 × 10%/mm Hg [95% CI -72·5 to -6·6; p=0·019) and with losartan compared with atenolol (-43·3 × 10%/mm Hg [-74·3 to -12·3]; p=0·0061). No deaths occurred. Two serious adverse events were recorded, one while taking amlodipine (diarrhoea with dehydration) and one while taking atenolol (fall with fracture), neither of which was related to study drug intake.
INTERPRETATION
4 weeks of treatment with amlodipine, losartan, or atenolol did not differ in their effects on cerebrovascular reactivity in people with sporadic small vessel disease but did result in differential treatment effects in patients with CADASIL. Whether antihypertensive drug classes differentially affect clinical outcomes in people with small vessel diseases requires further research.
FUNDING
EU Horizon 2020 programme.
Topics: Humans; Middle Aged; Aged; Antihypertensive Agents; Blood Pressure; Losartan; Atenolol; CADASIL; Cross-Over Studies; Treatment Outcome; Hypertension; Amlodipine; Double-Blind Method
PubMed: 37863608
DOI: 10.1016/S1474-4422(23)00293-4 -
Cell Nov 2023Ca1.2 channels play crucial roles in various neuronal and physiological processes. Here, we present cryo-EM structures of human Ca1.2, both in its apo form and in...
Ca1.2 channels play crucial roles in various neuronal and physiological processes. Here, we present cryo-EM structures of human Ca1.2, both in its apo form and in complex with several drugs, as well as the peptide neurotoxin calciseptine. Most structures, apo or bound to calciseptine, amlodipine, or a combination of amiodarone and sofosbuvir, exhibit a consistent inactivated conformation with a sealed gate, three up voltage-sensing domains (VSDs), and a down VSD. Calciseptine sits on the shoulder of the pore domain, away from the permeation path. In contrast, when pinaverium bromide, an antispasmodic drug, is inserted into a cavity reminiscent of the IFM-binding site in Na channels, a series of structural changes occur, including upward movement of VSD coupled with dilation of the selectivity filter and its surrounding segments in repeat III. Meanwhile, S4-5 merges with S5 to become a single helix, resulting in a widened but still non-conductive intracellular gate.
Topics: Humans; Calcium Channels, L-Type; Elapid Venoms; Neurotoxins; Protein Domains; Cryoelectron Microscopy
PubMed: 37972591
DOI: 10.1016/j.cell.2023.10.007 -
American Journal of Cardiovascular... Jul 2023Few data are available regarding the efficacy and safety of a single-pill combination (SPC) consisting of four medications in patients with concomitant hypertension and... (Randomized Controlled Trial)
Randomized Controlled Trial
A Randomized, Multicenter, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of a Quadruple Combination of Amlodipine, Losartan, Rosuvastatin, and Ezetimibe in Patients with Concomitant Essential Hypertension and Dyslipidemia.
BACKGROUND
Few data are available regarding the efficacy and safety of a single-pill combination (SPC) consisting of four medications in patients with concomitant hypertension and dyslipidemia.
OBJECTIVE
We aimed to determine the efficacy and tolerability of a fixed-dose SPC consisting of 5 mg amlodipine, 100 mg losartan, 20 mg rosuvastatin, and 10 mg ezetimibe (A/L/R/E) in patients with concomitant hypertension and dyslipidemia.
METHODS
This was a 14-week, randomized, multicenter, double-blind, placebo-controlled, phase III clinical trial. In total, 145 patients were randomized to receive A/L/R/E, A/L, or L/R/E. The primary endpoints were the average change in the low-density lipoprotein cholesterol (LDL-C) level in the A/L/R/E and A/L groups and the sitting systolic blood pressure (sitSBP) in the A/L/R/E and L/R/E groups. The numbers of patients with adverse drug reactions (ADRs) were compared as safety variables.
RESULTS
The average percentage change in the LDL-C level as the least squares mean (LSM) from the baseline LDL-C level at the end of the 8-week treatment was - 59.0% in the A/L/R/E group and 0.2% in the A/L group (LSM difference - 59.2, 95% confidence interval [CI] - 68.1 to - 50.4; p < 0.0001). The average change in the sitSBP as the LSM was - 15.8 mmHg in the A/L/R/E group and -4.7 mmHg in the L/R/E group (LSM difference - 11.1, 95% CI - 16.8 to - 5.4; p = 0.0002). No ADRs occurred in the A/L/R/E group.
CONCLUSIONS
A/L/R/E as an SPC could be an effective treatment for patients with hypertension and dyslipidemia without significant safety issues.
CLINICAL TRIALS REGISTRATION
NCT04074551 (registered 30 August 2019).
Topics: Humans; Losartan; Rosuvastatin Calcium; Antihypertensive Agents; Ezetimibe; Cholesterol, LDL; Blood Pressure; Amlodipine; Hypertension; Essential Hypertension; Dyslipidemias; Double-Blind Method; Treatment Outcome
PubMed: 37395974
DOI: 10.1007/s40256-023-00590-9 -
The Medical Letter on Drugs and... May 2024
Review
Topics: Humans; Hypertension; Antihypertensive Agents; Blood Pressure
PubMed: 38771738
DOI: 10.58347/tml.2024.1703a -
MMW Fortschritte Der Medizin Aug 2023
Topics: Humans; Antihypertensive Agents; Indapamide; Amlodipine
PubMed: 37537471
DOI: 10.1007/s15006-023-2868-1 -
Drug Metabolism Reviews Aug 2023Orally administered drugs undergo four stages of absorption, distribution, metabolism, and excretion in the body. However, before being absorbed into the body, orally... (Review)
Review
Orally administered drugs undergo four stages of absorption, distribution, metabolism, and excretion in the body. However, before being absorbed into the body, orally administered drugs contact with gut microbiota, which catalyze their metabolic reactions such as reduction, hydroxylation (including deconjugation), dehydrogenation, acetylation, etc. Although these metabolic reactions typically inactivate drugs (ranitidine, digoxin, and amlodipine), some activate them (sulfasalazine). The composition and quantity of gut microbiota are variable across individuals and fluctuated by gut microbiota modulators such as diets, drugs (antibiotics), probiotics, prebiotics, pathogen infections, and stressors. Gut microbiota-involved metabolisms of drugs in the gastrointestinal tract are dependent on the composition and quantity of gut microbiota. Therefore, the bioavailability of orally administered drugs is significantly affected by gut microbiota modulators. This review describes gut microbiota modulator-drug interactions.
Topics: Humans; Gastrointestinal Microbiome; Probiotics; Prebiotics; Gastrointestinal Tract; Anti-Bacterial Agents
PubMed: 36999361
DOI: 10.1080/03602532.2023.2197178