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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 -
Archives of Gynecology and Obstetrics Dec 2022There is a lack of sufficient evidence regarding efficacy and safety of amlodipine on treating hypertension during pregnancy. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is a lack of sufficient evidence regarding efficacy and safety of amlodipine on treating hypertension during pregnancy.
OBJECTIVE
To compare antihypertensive efficacy, pregnancy outcome and safety of amlodipine with nifedipine on hypertension during pregnancy.
METHODS
A systematic search of PubMed, Embase, Cochrane Library, clinicaltrials.gov, Chinese National Knowledge Infrastructure, Wanfang Database and China Biology Medicine disc of randomized controlled trials (RCTs) up to April l5, 2021 was conducted on RCTs comparing amlodipine to nifedipine for the treatment of hypertension during pregnancy. Screening, data extraction, and quality assessment were done by two independent reviewers. To estimate relative effects from all available evidence, a meta-analysis was conducted.
RESULTS
Seventeen RCTs were included. Amlodipine was found the efficacy is slightly superior to nifedipine on treating hypertension during pregnancy (RR 1.06, 95% CI 1.01 to 1.10) with a decreased risk for maternal side effects (RR 0.42, 95% CI 0.29 to 0.61). Subgroup analysis found amlodipine can get a better control on SBP (RR - 11.68, 95% CI - 17.98 to - 5.37) and DBP (RR - 7.44, 95% CI - 13.81 to - 1.06) compared with intermediate-/long-acting nifedipine. In addition, there was no difference between amlodipine and nifedipine on pregnancy outcomes including caesarean section, premature labour, placental abruption, FGR, fetal distress, neonatal asphyxia.
CONCLUSIONS
Given the results of this systematic review and meta-analysis, amlodipine can be effectively and safely used for hypertension during pregnancy.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Nifedipine; Amlodipine; Hypertension; Pregnancy Outcome; Obstetric Labor, Premature
PubMed: 35305140
DOI: 10.1007/s00404-022-06504-5 -
Ugeskrift For Laeger Apr 2023Pedal oedema is a well-known adverse effect of amlodipine, but significantly less frequent if only half of the maximum recommended dosage is used. Diuretics are... (Review)
Review
Pedal oedema is a well-known adverse effect of amlodipine, but significantly less frequent if only half of the maximum recommended dosage is used. Diuretics are ineffective. To cause as few side effects as possible, options for managing are prioritised in this review: Reduce dosage, switch to lercanidipine/lacidipine, switch to another group, add/increase dosage of an ACE-inhibitor/angiotensin II-receptor blocker, administer at night, or switch to verapamil/diltiazem. Non-pharmacologic actions or observation may be considered when the oedemas are mild and not bothersome.
Topics: Humans; Amlodipine; Calcium Channel Blockers; Hypertension; Ankle; Edema; Drug-Related Side Effects and Adverse Reactions
PubMed: 37114573
DOI: No ID Found -
Journal of Clinical Hypertension... Oct 2020Single risk factors, such as hypertension and dyslipidemia, can combine to exacerbate the development and severity of cardiovascular disease. Treatment goals may be more... (Randomized Controlled Trial)
Randomized Controlled Trial
Single risk factors, such as hypertension and dyslipidemia, can combine to exacerbate the development and severity of cardiovascular disease. Treatment goals may be more effectively achieved if multiple disease factors are targeted with combination treatment. We enrolled 202 patients who were randomly divided into the following three groups: telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg, telmisartan 80 mg + rosuvastatin 20 mg, and telmisartan/amlodipine 80/5 mg. The primary efficacy variables were changes from baseline in mean sitting systolic blood pressure (MSSBP) between telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan 80 mg + rosuvastatin 20 mg at 8 weeks, and the percent changes from baseline in low-density lipoprotein (LDL) cholesterol between telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan/amlodipine 80/5 mg at 8 weeks. The secondary efficacy variables were changes in MSSBP, mean sitting diastolic blood pressure (MSDBP), LDL cholesterol and other lipid levels at 4 weeks and 8 weeks, as well as observed adverse events during follow-up. There were no significant differences between the three groups in demographic characteristics and no significant difference among the three groups in terms of baseline characteristics for the validity evaluation variables. The mean overall treatment compliance in the three groups was, respectively, 98.42%, 96.68%, and 98.12%, indicating strong compliance for all patients. The Least-Square (LS) mean (SE) for changes in MSSBP in the two (telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan 80 mg + rosuvastatin 20 mg) groups were -19.3 (2.68) mm Hg and -6.69 (2.76) mm Hg. The difference between the two groups was significant (-12.60 (2.77) mm Hg, 95% CI -18.06 to -7.14, P < .0001). The LS Mean for the percent changes from baseline in LDL cholesterol in the two (telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan/amlodipine 80/5 mg) groups were -52.45 (3.23) % and 2.68 (3.15) %. The difference between the two groups was significant (-55.13 (3.20) %, 95% CI -61.45 to -48.81, P < .0001). There were no adverse events leading to discontinuation or death. Combined administration of telmisartan/amlodipine 80/5 mg and rosuvastatin 20 mg for the treatment of hypertensive patients with dyslipidemia significantly reduces blood pressure and improves lipid control. ClinicalTrials.gov identifier: NCT03067688.
Topics: Aged; Amlodipine; Antihypertensive Agents; Blood Pressure; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Dyslipidemias; Female; Humans; Hypertension; Male; Middle Aged; Rosuvastatin Calcium; Telmisartan
PubMed: 32937023
DOI: 10.1111/jch.13893 -
British Journal of Pharmacology May 2022Non-alcoholic fatty liver disease (NAFLD) represents a severe public health problem. It often coexists with hypertension in the context of metabolic syndrome. We...
BACKGROUND AND PURPOSE
Non-alcoholic fatty liver disease (NAFLD) represents a severe public health problem. It often coexists with hypertension in the context of metabolic syndrome. We investigated the effects of amlodipine on NAFLD combined with hypertension and investigated the underlying mechanism/s.
EXPERIMENTAL APPROACH
Mice were fed with high-fat diet (HFD) and 0.05% N-nitro-L-arginine methylester sterile water to induce NAFLD with hypertension. Gut microbiota composition and function were assessed by 16S ribosomal DNA and metagenomic sequencing. Untargeted metabolome profiles were applied to identify differential metabolites in mice caecum.
KEY RESULTS
Amlodipine besylate and amlodipine aspartate significantly decreased liver injury and hepatic steatosis, and improved lipid metabolism with a concomitant reduction in the expression of lipogenic genes in mice with NAFLD and hypertension. Mechanistically, amlodipine besylate and amlodipine aspartate have potential to restore intestinal barrier integrity and improve antimicrobial defence, along with the elevated abundances of Akkermansia, Bacteroides and Lactobacillus. Noteworthily, the gut microbiota in amlodipine besylate- and amlodipine aspartate-treated mice had higher abundance of functional genes involved in taurine and hypotaurine metabolism. Consistently, the strengthened taurine and hypotaurine metabolism was confirmed by untargeted metabolome analysis. Based on the correlation and causal analysis, the altered gut microbiota composition and the enhancement of taurine and hypotaurine metabolism may synergistically decreased alanine aminotransferase, liver triglycerides, lipogenic genes and plasma cholesterol in HFD-fed hypertensive mice.
CONCLUSION AND IMPLICATIONS
Amlodipine besylate and amlodipine aspartate exert multifactorial improvements in NAFLD and hypertension by modulating gut microbiota. They may serve as promising therapeutic agents for treating these diseases.
Topics: Amlodipine; Animals; Antihypertensive Agents; Diet, High-Fat; Gastrointestinal Microbiome; Mice; Non-alcoholic Fatty Liver Disease
PubMed: 34862599
DOI: 10.1111/bph.15768 -
Hipertension Y Riesgo Vascular 2021Hypertension (HTN) in pregnancy is defined as systolic blood pressure ≥ 140 and/or diastolic blood pressure ≥ 90 mmHg. Based on the values, it is classified as...
Hypertension (HTN) in pregnancy is defined as systolic blood pressure ≥ 140 and/or diastolic blood pressure ≥ 90 mmHg. Based on the values, it is classified as non-severe (< 160/110 mmHg) and severe (≥ 160/110 mmHg). Before starting treatment in non-severe HTN, white- coat HTN should be ruled out. If outpatient management is possible, pharmacological initiation is suggested with sustained high values, avoiding < 120/80 mmHg. Safe drugs during pregnancy are methyldopa, labetalol, and nifedipine-retard. The use of nifedipine-XL or amlodipine can be considered with a lower level of evidence of safety. Diuretics, atenolol, and other beta-blockers for antihypertensive purposes is not recommended in this period. Renin-angiotensin-aldosterone system inhibitors are strictly contraindicated. In postpartum and breastfeeding, the same therapeutic regimen used during pregnancy can be maintained, trying early withdrawal of methyldopa. During puerperium, amlodipine and enalapril are safe, with minimal excretion in breast milk.
Topics: Amlodipine; Antihypertensive Agents; Blood Pressure; Breast Feeding; Female; Humans; Hypertension; Methyldopa; Nifedipine; Postpartum Period; Pregnancy
PubMed: 33632659
DOI: 10.1016/j.hipert.2021.01.002 -
Proceedings of the National Academy of... May 2022There is currently no effective treatment for pancreatic ductal adenocarcinoma (PDAC). While palliative chemotherapy offers a survival benefit to most patients, nearly...
There is currently no effective treatment for pancreatic ductal adenocarcinoma (PDAC). While palliative chemotherapy offers a survival benefit to most patients, nearly all will eventually progress on treatment and long-term survivability remains poor. Given the lack of subsequent line treatment options, in this study, we sought to identify novel strategies to prevent, delay, or overcome resistance to gemcitabine, one of the most widely used medications in PDAC. Using a combination of single-cell RNA sequencing and high-throughput proteomic analysis, we identified a subset of gemcitabine-resistant tumor cells enriched for calcium/calmodulin signaling. Pharmacologic inhibition of calcium-dependent calmodulin activation led to the rapid loss of drug-resistant phenotypes in vitro, which additional single-cell RNA sequencing identified was due to impaired activation of the RAS/ERK signaling pathway. Consistent with these observations, calcium chelation or depletion of calcium in the culture media also impaired ERK activation in gemcitabine-resistant cells, and restored therapeutic responses to gemcitabine in vitro. We observed similar results using calcium channel blockers (CCBs) such as amlodipine, which inhibited prosurvival ERK signaling in vitro and markedly enhanced therapeutic responses to gemcitabine in both orthotopic xenografts and transgenic models of PDAC. Combined, these results offer insight into a potential means of gemcitabine resistance and suggest that select CCBs may provide a clinical benefit to PDAC patients receiving gemcitabine-based chemotherapy.
Topics: Amlodipine; Animals; Antineoplastic Agents; Calcium Channel Blockers; Calmodulin; Deoxycytidine; Humans; Pancreatic Neoplasms; United States; Gemcitabine
PubMed: 35476525
DOI: 10.1073/pnas.2200143119 -
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 -
Journal of Hypertension Apr 2020
Topics: Amlodipine; Blood Pressure; Feasibility Studies; Indapamide; Perindopril
PubMed: 32132437
DOI: 10.1097/HJH.0000000000002389 -
MMW Fortschritte Der Medizin Aug 2023
Topics: Humans; Antihypertensive Agents; Indapamide; Amlodipine
PubMed: 37537471
DOI: 10.1007/s15006-023-2868-1