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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 -
JAMA Apr 2023Hypertension is the leading risk factor for premature death worldwide. Multiple blood pressure-lowering therapies are available but the potential for maximizing benefit... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Hypertension is the leading risk factor for premature death worldwide. Multiple blood pressure-lowering therapies are available but the potential for maximizing benefit by personalized targeting of drug classes is unknown.
OBJECTIVE
To investigate and quantify the potential for targeting specific drugs to specific individuals to maximize blood pressure effects.
DESIGN, SETTING, AND PARTICIPANTS
A randomized, double-blind, repeated crossover trial in men and women with grade 1 hypertension at low risk for cardiovascular events at an outpatient research clinic in Sweden. Mixed-effects models were used to assess the extent to which individuals responded better to one treatment than another and to estimate the additional blood pressure lowering achievable by personalized treatment.
INTERVENTIONS
Each participant was scheduled for treatment in random order with 4 different classes of blood pressure-lowering drugs (lisinopril [angiotensin-converting enzyme inhibitor], candesartan [angiotensin-receptor blocker], hydrochlorothiazide [thiazide], and amlodipine [calcium channel blocker]), with repeated treatments for 2 classes.
MAIN OUTCOMES AND MEASURES
Ambulatory daytime systolic blood pressure, measured at the end of each treatment period.
RESULTS
There were 1468 completed treatment periods (median length, 56 days) recorded in 270 of the 280 randomized participants (54% men; mean age, 64 years). The blood pressure response to different treatments varied considerably between individuals (P < .001), specifically for the choices of lisinopril vs hydrochlorothiazide, lisinopril vs amlodipine, candesartan vs hydrochlorothiazide, and candesartan vs amlodipine. Large differences were excluded for the choices of lisinopril vs candesartan and hydrochlorothiazide vs amlodipine. On average, personalized treatment had the potential to provide an additional 4.4 mm Hg-lower systolic blood pressure.
CONCLUSIONS AND RELEVANCE
These data reveal substantial heterogeneity in blood pressure response to drug therapy for hypertension, findings that may have implications for personalized therapy.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02774460.
Topics: Female; Humans; Male; Middle Aged; Amlodipine; Antihypertensive Agents; Blood Pressure; Hydrochlorothiazide; Hypertension; Lisinopril; Double-Blind Method; Cross-Over Studies; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Diuretics; Calcium Channel Blockers; Precision Medicine
PubMed: 37039792
DOI: 10.1001/jama.2023.3322 -
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 -
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 -
American Family Physician Nov 2020Drugs are being prescribed with more frequency and in higher quantities. A serious adverse drug event from prescribed medications constitutes 2.4% to 16.2% of all...
Drugs are being prescribed with more frequency and in higher quantities. A serious adverse drug event from prescribed medications constitutes 2.4% to 16.2% of all hospital admissions. Many of the adverse drug events present intraorally or periorally in isolation or as a clinical symptom of a systemic effect. Clinical recognition and treatment of adverse drug events are important to increase patient adherence, manage drug therapy, or detect early signs of potentially serious outcomes. Oral manifestations of commonly prescribed medications include gingival enlargement, oral hyperpigmentation, oral hypersensitivity reaction, medication-related osteonecrosis, xerostomia, and other oral or perioral conditions. To prevent dose-dependent adverse drug reactions, physicians should prescribe medications judiciously using the lowest effective dose with minimal duration. Alternatively, for oral hypersensitivity reactions that are not dose dependent, quick recognition of clinical symptoms associated with time-dependent drug onset can allow for immediate discontinuation of the medication without discontinuation of other medications. Physicians can manage oral adverse drug events in the office through oral hygiene instructions for gingival enlargement, medication discontinuation for oral pigmentation, and prescription of higher fluoride toothpastes for xerostomia.
Topics: Albuterol; Amlodipine; Anticonvulsants; Antihypertensive Agents; Atorvastatin; Bisphosphonate-Associated Osteonecrosis of the Jaw; Bronchodilator Agents; Deprescriptions; Drug Hypersensitivity; Fluorides; Gingival Overgrowth; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperpigmentation; Hypoglycemic Agents; Lisinopril; Losartan; Metformin; Metoprolol; Mouth Diseases; Omeprazole; Oral Hygiene; Proton Pump Inhibitors; Simvastatin; Thyroxine; Toothpastes; Xerostomia
PubMed: 33179891
DOI: No ID Found -
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 -
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