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American Journal of Cardiovascular... Apr 2016
Erratum to: Efficacy and Safety Study of Olmesartan Medoxomil, Amlodipine, and Hydrochlorothiazide Combination Therapy in Patients with Hypertension Not Controlled with Olmesartan Medoxomil and Hydrochlorothiazide Combination Therapy: Results of a Randomized, Double-Blind, Multicenter Trial.
PubMed: 26994003
DOI: 10.1007/s40256-016-0167-2 -
High Blood Pressure & Cardiovascular... Dec 2017Despite the improvements in the management of hypertension during the last three decades, it continues to be one of the leading causes of cardiovascular morbidity and...
Despite the improvements in the management of hypertension during the last three decades, it continues to be one of the leading causes of cardiovascular morbidity and mortality worldwide. Effective and sustained reductions in blood pressure (BP) reduce the incidence of myocardial infarction, stroke, congestive heart failure and cardiovascular death. However, the proportion of patients who achieve the recommended BP goal (< 140/90 mmHg) is persistently low, worldwide. Poor adherence to therapy, complex therapeutic regimens, clinical inertia, drug-related adverse events and multiple risk factors or comorbidities contribute to the disparity between the potential and actual BP control rate. Previously we published a practical therapeutic platform for the treatment of hypertension based on clinical evidence, guidelines, best practice and clinical experience. This platform provides a personalised treatment approach and can be used to improve BP control and simplify treatment. It uses long-acting, effective and well-tolerated angiotensin receptor blocker (ARB) olmesartan, in combination with a calcium channel blocker amlodipine, and/or a thiazide diuretic hydrochlorothiazide. These drugs were selected based on the availability in most European Countries of single-pill, fixed formulations in a wide range of doses for both dual- and triple-drug combinations. The platform approach could be applied to other ARBs or angiotensin-converting enzyme inhibitors available in single-pill, fixed-dose combinations. Here, we present an update, which takes into account the results of the recently published studies and extends the applicability of the platform to common conditions that are often neglected or poorly considered in clinical practice guidelines.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Drug Combinations; Evidence-Based Medicine; Humans; Hypertension; Medication Adherence; Patient Selection; Risk Factors; Sodium Chloride Symporter Inhibitors; Treatment Outcome
PubMed: 29086364
DOI: 10.1007/s40292-017-0239-7 -
Journal of Clinical Hypertension... Dec 2017Antihypertensive monotherapy is often insufficient to control blood pressure (BP). Several recent guidelines advocate for initial combination drug therapy in many... (Meta-Analysis)
Meta-Analysis
Antihypertensive monotherapy is often insufficient to control blood pressure (BP). Several recent guidelines advocate for initial combination drug therapy in many patients. This meta-analysis of seven randomized, double-blind studies (N = 5888) evaluated 8 weeks of olmesartan medoxomil (OM)-based single-pill dual-combination therapy (OM+amlodipine/azelnidipine or hydrochlorothiazide) vs OM monotherapy in adults with hypertension. BP-lowering efficacy, goal achievement, and adverse events were assessed in the full cohort and subgroups (elderly/nonelderly and patients with and without chronic kidney disease). In the full cohort at week 8, for dual therapy vs monotherapy, seated BP was lower (137.5/86.1 mm Hg vs 144.4/89.9 mm Hg), and the mean change from baseline in BP and BP goal achievement (<140/90 mm Hg) were greater (-22.7/-15.0 mm Hg vs -16.0/-11.3 mm Hg and 51.2% vs 34.7%, respectively). Adverse events were similar between groups. BP-lowering efficacy among subgroups mirrored the findings in the full cohort whereby changes were significantly greater following OM dual-combination therapy vs OM monotherapy.
Topics: Age Factors; Antihypertensive Agents; Drug Therapy, Combination; Humans; Hypertension; Imidazoles; Renal Insufficiency, Chronic; Tetrazoles; Treatment Outcome
PubMed: 29067756
DOI: 10.1111/jch.13103 -
Journal of Clinical Hypertension... Feb 2018The efficacy and safety of olmesartan medoxomil (OM) vs active control (AC) monotherapy among elderly patients aged 60-79 years (N = 4487) was evaluated by... (Meta-Analysis)
Meta-Analysis
The efficacy and safety of olmesartan medoxomil (OM) vs active control (AC) monotherapy among elderly patients aged 60-79 years (N = 4487) was evaluated by meta-analysis (25 studies). In all patients, change from baseline to end point in blood pressure (BP) was significantly greater with OM vs AC (-19.5/-11.9 vs -16.8/-10.7 mm Hg). Greater proportions of OM- vs AC-treated patients achieved BP goals. In patients with impaired renal function (estimated glomerular filtration rate <60 mL/min/1.73 m ), OM treatment resulted in a greater mean change from baseline in systolic BP vs AC (-21.2 vs -18.7 mm Hg, respectively) and a greater proportion of patients achieving BP goals. These parameters were similar in both groups for elderly patients with diabetes. OM was well tolerated with few adverse events. OM monotherapy can be used as an initial treatment for hypertension in elderly patients, including those with renal impairment or diabetes.
Topics: Aged; Angiotensin Receptor Antagonists; Blood Pressure; Humans; Hypertension; Middle Aged; Olmesartan Medoxomil; Treatment Outcome
PubMed: 29462508
DOI: 10.1111/jch.13183 -
Basic & Clinical Pharmacology &... Jul 2016Amiodarone (AD) is one of the most frequently prescribed anti-arrhythmic agents worldwide, but its effectiveness is limited due to the development of pulmonary toxicity....
Amiodarone (AD) is one of the most frequently prescribed anti-arrhythmic agents worldwide, but its effectiveness is limited due to the development of pulmonary toxicity. Several lines of evidence have suggested that AT1 receptor antagonists can attenuate pulmonary fibrosis in different animal models. This study was performed to evaluate the effect of olmesartan medoxomil (OM) on lung injury induced in rats by AD which was assessed biochemically (hydroxyproline content, MDA level and SOD activity), histologically (Ashcroft criteria and Masson's trichrome stain) and immunohistochemically (TGF-β1 expression in lung tissue). The expression levels of TGF-β1 and type I collagen mRNA were also determined by quantitative real-time polymerase chain reaction. Forty-eight adult male rats were randomized into six equal groups: control group, OM control groups, AD group received 40 mg/kg/day, p.o. for 4 weeks to induce pulmonary injury in rats and OM-treated groups received 0.6 and 6 mg/kg/day, p.o. concomitantly with AD for the same period. The results indicated that OM significantly decreased collagen deposition and hydroxyproline content, ameliorated pathological score and decreased the elevation in type I collagen and TGF-ß1 mRNA expression in lung tissue. Furthermore, it attenuated the AD-induced increase in the MDA level and increased SOD activity in lung tissue. It can be concluded that OM exerts a protective effect against AD-induced lung damage in rats which is attributed to modulation of pro-fibrogenic cytokine (TGF-β1) and antioxidant effect.
Topics: Amiodarone; Animals; Collagen Type I; Disease Models, Animal; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Lung; Lung Injury; Male; Olmesartan Medoxomil; RNA, Messenger; Random Allocation; Rats; Rats, Sprague-Dawley; Transforming Growth Factor beta1
PubMed: 26781185
DOI: 10.1111/bcpt.12551 -
BMC Pharmacology & Toxicology Jun 2017Tardive akathisia (TA) is a subtype of tardive syndrome, and its etiology is still uncertain. Sevikar is an anti-hypertensive agent containing both amlodipine and...
BACKGROUND
Tardive akathisia (TA) is a subtype of tardive syndrome, and its etiology is still uncertain. Sevikar is an anti-hypertensive agent containing both amlodipine and olmesartan, and has never been reported to have an adverse reaction in patients with tardive syndrome.
CASE PRESENTATION
A 57-year-old woman who took Sevikar for hypertension for 10 years developed TA one and a half years before receiving any psychiatric treatment. After switching from Sevikar to bisoprolol, she reported obvious improvement in her akathisia.
CONCLUSIONS
It is noteworthy that her TA developed before receiving any antidepressant medication, and that her TA improved after discontinuation of Sevikar. In light of these pharmacodynamic properties, it is therefore concluded that use of amlodipine and olmesartan might have caused TA in this patient. We reported this rare case to remind clinicians to be aware of possible akathisia when using amlodipine and olmesartan in combination as anti-hypertensive agents.
Topics: Akathisia, Drug-Induced; Amlodipine Besylate, Olmesartan Medoxomil Drug Combination; Antihypertensive Agents; Female; Humans; Middle Aged
PubMed: 28583166
DOI: 10.1186/s40360-017-0148-3 -
Drug Design, Development and Therapy 2015A fixed-dose combination of amlodipine and olmesartan is used to treat high blood pressure in patients whose hypertension is not sufficiently controlled with either drug... (Comparative Study)
Comparative Study Randomized Controlled Trial
A fixed-dose combination of amlodipine and olmesartan is used to treat high blood pressure in patients whose hypertension is not sufficiently controlled with either drug alone. The objective of this study was to evaluate the bioequivalence of two fixed-dose combinations, ie, amlodipine orotate/olmesartan medoxomil 10/40 mg and amlodipine besylate/olmesartan medoxomil 10/40 mg, in healthy subjects. A randomized, open-label, single-dose, two-sequence, two-period, crossover study was conducted in 30 healthy adult volunteers. Blood samples were collected for up to 72 hours post-dose in each period. Safety data included the results of physical examinations, clinical laboratory tests, vital signs, an electrocardiogram, and adverse events. For both amlodipine and olmesartan, the 90% confidence intervals for the geometric mean ratios of AUClast and time to peak plasma concentration fell within the bioequivalence acceptance criteria. The two fixed-dose combinations showed similar safety profiles. Amlodipine orotate/olmesartan medoxomil 10/40 mg was bioequivalent to amlodipine besylate/olmesartan medoxomil 10/40 mg.
Topics: Adult; Amlodipine Besylate, Olmesartan Medoxomil Drug Combination; Antihypertensive Agents; Area Under Curve; Cross-Over Studies; Female; Humans; Male; Middle Aged; Salts; Therapeutic Equivalency; Young Adult
PubMed: 26082611
DOI: 10.2147/DDDT.S82820 -
Gut Microbes 2023Prodrugs reliant on microbial activation are widely used but exhibit a range of efficacies that remain poorly understood. The anti-inflammatory compound 5-aminosalicylic...
Prodrugs reliant on microbial activation are widely used but exhibit a range of efficacies that remain poorly understood. The anti-inflammatory compound 5-aminosalicylic acid (5-ASA), which is packaged in a variety of azo-linked prodrugs provided to most Ulcerative Colitis (UC) patients, shows confounding inter-individual variabilities in response. Such prodrugs must be activated by azo-bond reduction to form 5-ASA, a process that has been attributed to both enzymatic and non-enzymatic catalysis. Gut microbial azoreductases (AzoRs) are the first catalysts shown to activate azo-linked drugs and to metabolize toxic azo-chemicals. Here, we chart the scope of the structural and functional diversity of AzoRs in health and in patients with the inflammatory bowel diseases (IBDs) UC and Crohn's Disease (CD). Using structural metagenomics, we define the landscape of gut microbial AzoRs in 413 healthy donor and 1059 IBD patient fecal samples. Firmicutes encode a significantly higher number of unique AzoRs compared to other phyla. However, structural and biochemical analyses of distinct AzoRs from the human microbiome reveal significant differences between prevalent orthologs in the processing of toxic azo-dyes, and their generally poor activation of IBD prodrugs. Furthermore, while individuals with IBD show higher abundances of AzoR-encoding gut microbial taxa than healthy controls, the overall abundance of AzoR-encoding microbes is markedly low in both disease and health. Together, these results establish that gut microbial AzoRs are functionally diverse but sparse in both health and disease, factors that may contribute to non-optimal processing of azo-linked prodrugs and idiopathic IBD drug responses.
Topics: Humans; Gastrointestinal Microbiome; Prodrugs; Amlodipine Besylate, Olmesartan Medoxomil Drug Combination; Crohn Disease; Colitis, Ulcerative; Mesalamine; Inflammatory Bowel Diseases
PubMed: 37122075
DOI: 10.1080/19490976.2023.2203963 -
Journal of Clinical Medicine Research Dec 2017Sprue-like enteropathy associated with olmesartan medoxomil use has been recently reported. Its clinical manifestations include diarrhea, weight loss and malabsorption....
Sprue-like enteropathy associated with olmesartan medoxomil use has been recently reported. Its clinical manifestations include diarrhea, weight loss and malabsorption. Duodenal biopsies show villous atrophy (VA) with or without intraepithelial lymphocytosis and inflammation of the lamina propria. Serology for celiac disease (CD) is negative and gluten-free diet does not result in clinical improvement. Symptoms resolve after olmesartan discontinuation. Follow-up biopsies show recovery/improvement of the duodenum. Whether sprue-like enteropathy is a specific adverse reaction to olmesartan or rather a class effect of angiotensin-receptor blockers (ARBs) remains a controversial issue. We report a case of sprue-like enteropathy associated with telmisartan. A 52-year-old man presented with chronic diarrhea, abdominal discomfort and significant weight loss. In the last 3 years, he had been treated with telmisartan 40 mg/day for hypertension after right adrenalectomy for an aldosterone-producing adenoma. Laboratory investigations showed no significant abnormalities: Hb 13.6 g/dL, serum albumin 3.9 g/dL, total cholesterol 193 mg/dL, serum creatinine 0.99 mg/dL, sodium 143.6 mmol/L, K 4.3 mmol/L, calcium 9.3 mg/dL, phosphorus 3.9 mg/dL and 25-OH-D3 27.7 ng/mL. Duodenal histology showed subtotal VA and inflammation of the lamina propria. CD serology was negative. HLA-DQ typing showed absence of the DQ2/DQ8 haplotypes. After telmisartan discontinuation, patient's symptoms subsided, and his body weight increased despite persistence of a gluten-containing diet. Follow-up biopsies at 3 showed progressive duodenal recovery. Very few cases of sprue-like enteropathy associated with ARBs other than olmesartan have been reported. Our case of telmisartan-associated enteropathy further suggests that sprue-like disease may be a class effect of ARBs.
PubMed: 29163738
DOI: 10.14740/jocmr3047w -
Gastroenterology Research Aug 2020Olmesartan is an angiotensin II receptor blocker (ARB) drug approved in 2002 for the treatment of hypertension. Since 2012, there have been reports of a rare adverse...
Olmesartan is an angiotensin II receptor blocker (ARB) drug approved in 2002 for the treatment of hypertension. Since 2012, there have been reports of a rare adverse effect suspected to be related to its use. The author presents a case of a 63-year-old female with refractory gastrointestinal (GI) symptoms including diarrhea with associated weight loss and severe electrolyte abnormalities necessitating hospitalization. An extensive inpatient evaluation ensued and was initially unremarkable. Esophagogastroduodenoscopy (EGD) discovered an endoscopically normal duodenum that was biopsied and notably revealed villous atrophy and intraepithelial lymphocytosis. Colonoscopy was normal appearing though biopsy findings were significant for nonspecific colitis. The endoscopy findings in the setting of the clinical presentation confirmed the diagnosis of olmesartan-associated enteropathy (OAE). Clinical improvement was noted after cessation of olmesartan and histological resolution was confirmed with repeat EGD post-discharge.
PubMed: 32864026
DOI: 10.14740/gr1301