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1.
Vasc Health Risk Manag ; 16: 41-51, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021227

RESUMO

This review aims to elucidate the optimal dosing of angiotensin receptor-neprilysin inhibitor (ARNI) therapy in the heart failure (HF) treatment paradigm through examination of the trial population characteristics and the mortality benefit observed in the Prospective Comparison of ARNI with angiotensin-converting enzyme inhibitor (ACEI) to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF; NCT01035255) trial. Considerations regarding the initiation and titration of sacubitril/valsartan, a first-in-class ARNI, will also be addressed. The approval of sacubitril/valsartan heralded the first novel pharmacological class in over a decade for the treatment of heart failure with reduced ejection fraction (HFrEF). The PARADIGM-HF trial showed that treatment with valsartan/valsartan reduced the risk of first occurrence of either cardiovascular death or HF-related hospitalization (composite primary endpoint) by 20% compared with enalapril in patients with HFrEF. The incremental benefits of treatment with valsartan/valsartan over enalapril demonstrated in the PARADIGM-HF trial led to strong recommendations for its use over ACEIs or angiotensin receptor blockers to further reduce morbidity and mortality in the 2016 and 2017 American College of Cardiology/American Heart Association/Heart Failure Society of America updates to the guidelines for the management of HF. Although the optimal timing for the initiation of valsartan/valsartan has yet to be determined, its early use is likely to have a positive impact on patient outcomes.


Assuntos
Aminobutiratos/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Inibidores de Proteases/uso terapêutico , Tetrazóis/uso terapêutico , Aminobutiratos/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Ensaios Clínicos como Assunto , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Neprilisina/antagonistas & inibidores , Inibidores de Proteases/efeitos adversos , Fatores de Risco , Tetrazóis/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
3.
Wien Klin Wochenschr ; 131(19-20): 493-501, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31471672

RESUMO

Over the past 5 years several case reports and cohort studies have been published that describe a sprue-like enteropathy (SLE) with abdominal pain, chronic diarrhea and weight loss, after taking angiotensin type 1 receptor blockers (ARB). The initial case series from the Mayo Clinic, which described 22 cases of olmesartan-induced SLE, was followed by numerous case descriptions for almost all ARBs. A total of 73 case reports have been described so far that show evidence of ARB-associated enteropathy with villous atrophy and full recovery 3-12 months after discontinuation of the sartan in question. Of these, 59 cases were olmesartan-associated cases of SLE, another 14 case reports have been published for telmisartan (4), valsartan (3), losartan (2), candesartan (1) and eprosartan (1). Based on the available cohort studies, ARB-associated intestinal malabsorption occurs in 9.8-14 cases per 100,000 patients treated with ARBs, the number treated to harm is over 31,000 patient-years. Although the majority of case reports have been published with olmesartan, in the cohort studies no clear difference within the ARBs can be ruled out. The SLE is rare but must be suspected and diagnostically investigated in every patient presenting with abdominal discomfort, chronic diarrhea and weight loss who is being treated with an ARB, after other causes have been ruled out. In such cases, discontinuing the ARB leads to a full recovery.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II , Enteropatias , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Antagonistas de Receptores de Angiotensina , Diarreia/induzido quimicamente , Humanos , Imidazóis/efeitos adversos , Enteropatias/induzido quimicamente , Enteropatias/patologia , Síndromes de Malabsorção/induzido quimicamente , Tetrazóis/efeitos adversos
4.
N Engl J Med ; 381(17): 1609-1620, 2019 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-31475794

RESUMO

BACKGROUND: The angiotensin receptor-neprilysin inhibitor sacubitril-valsartan led to a reduced risk of hospitalization for heart failure or death from cardiovascular causes among patients with heart failure and reduced ejection fraction. The effect of angiotensin receptor-neprilysin inhibition in patients with heart failure with preserved ejection fraction is unclear. METHODS: We randomly assigned 4822 patients with New York Heart Association (NYHA) class II to IV heart failure, ejection fraction of 45% or higher, elevated level of natriuretic peptides, and structural heart disease to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or valsartan (target dose, 160 mg twice daily). The primary outcome was a composite of total hospitalizations for heart failure and death from cardiovascular causes. Primary outcome components, secondary outcomes (including NYHA class change, worsening renal function, and change in Kansas City Cardiomyopathy Questionnaire [KCCQ] clinical summary score [scale, 0 to 100, with higher scores indicating fewer symptoms and physical limitations]), and safety were also assessed. RESULTS: There were 894 primary events in 526 patients in the sacubitril-valsartan group and 1009 primary events in 557 patients in the valsartan group (rate ratio, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P = 0.06). The incidence of death from cardiovascular causes was 8.5% in the sacubitril-valsartan group and 8.9% in the valsartan group (hazard ratio, 0.95; 95% CI, 0.79 to 1.16); there were 690 and 797 total hospitalizations for heart failure, respectively (rate ratio, 0.85; 95% CI, 0.72 to 1.00). NYHA class improved in 15.0% of the patients in the sacubitril-valsartan group and in 12.6% of those in the valsartan group (odds ratio, 1.45; 95% CI, 1.13 to 1.86); renal function worsened in 1.4% and 2.7%, respectively (hazard ratio, 0.50; 95% CI, 0.33 to 0.77). The mean change in the KCCQ clinical summary score at 8 months was 1.0 point (95% CI, 0.0 to 2.1) higher in the sacubitril-valsartan group. Patients in the sacubitril-valsartan group had a higher incidence of hypotension and angioedema and a lower incidence of hyperkalemia. Among 12 prespecified subgroups, there was suggestion of heterogeneity with possible benefit with sacubitril-valsartan in patients with lower ejection fraction and in women. CONCLUSIONS: Sacubitril-valsartan did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among patients with heart failure and an ejection fraction of 45% or higher. (Funded by Novartis; PARAGON-HF ClinicalTrials.gov number, NCT01920711.).


Assuntos
Aminobutiratos/administração & dosagem , Antagonistas de Receptores de Angiotensina/administração & dosagem , Doenças Cardiovasculares/mortalidade , Insuficiência Cardíaca/tratamento farmacológico , Hospitalização/estatística & dados numéricos , Neprilisina/antagonistas & inibidores , Tetrazóis/administração & dosagem , Valsartana/administração & dosagem , Idoso , Aminobutiratos/efeitos adversos , Angioedema/induzido quimicamente , Antagonistas de Receptores de Angiotensina/efeitos adversos , Método Duplo-Cego , Feminino , Seguimentos , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipotensão/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Fatores Sexuais , Método Simples-Cego , Volume Sistólico , Tetrazóis/efeitos adversos , Valsartana/efeitos adversos
5.
Neurology ; 93(6): e559-e567, 2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31292226

RESUMO

OBJECTIVE: To evaluate the effect of cenobamate in patients with photoparoxysmal-EEG response (PPR) to intermittent photic stimulation (IPS) as proof of principle of efficacy in patients with epilepsy. METHODS: In this multicenter, single-blind study, adults with photosensitive epilepsy, with/without concomitant antiepileptic drug therapy, underwent IPS under 3 eye conditions after a single dose of placebo (day -1, day 2) or cenobamate (day 1; 100, 250, or 400 mg). Complete suppression was a standardized photosensitivity range reduction to 0 over ≥1 time points for all eye conditions. Partial suppression was a ≥3-point reduction over ≥3 testing times vs the same time points on day -1 in ≥1 eye condition. Pharmacokinetics and safety were assessed. RESULTS: Of 6 evaluable patients, 5 reentered to receive higher doses. Cenobamate 100 mg produced partial suppression in 1 of 3 patients; 250 mg produced complete suppression in 1 of 4 and partial suppression in 4 of 4 patients; and 400 mg produced complete suppression in 1 of 4 and partial suppression in 2 of 4 patients. PPR was consistently reduced on days 1 and 2 (>24 hours after cenobamate) vs day -1 (placebo) with the 250- and 400-mg doses. Area under the plasma concentration-time curve (before dose to last measurable concentration) values between 201 and 400 µg/h/mL resulted in partial suppression in 4 of 6 (66%) patients. Most common adverse events were dizziness and somnolence. CONCLUSIONS: This proof-of-principle study demonstrated that cenobamate is a potentially effective product for epilepsy. CLINICALTRIALSGOV IDENTIFIER: NCT00616148. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that, for patients with photosensitive epilepsy, cenobamate suppresses IPS-induced PPR.


Assuntos
Anticonvulsivantes/uso terapêutico , Carbamatos/uso terapêutico , Clorofenóis/uso terapêutico , Epilepsia Reflexa/tratamento farmacológico , Tetrazóis/uso terapêutico , Adolescente , Adulto , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/farmacocinética , Área Sob a Curva , Carbamatos/efeitos adversos , Carbamatos/farmacocinética , Clorofenóis/efeitos adversos , Clorofenóis/farmacocinética , Relação Dose-Resposta a Droga , Eletroencefalografia , Feminino , Humanos , Masculino , Estimulação Luminosa , Método Simples-Cego , Tetrazóis/efeitos adversos , Tetrazóis/farmacocinética , Adulto Jovem
6.
Acta Gastroenterol Belg ; 82(2): 319-321, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31314195

RESUMO

Olmesartan, an angiotensin receptor blocker, is a widely spread antihypertensive drug. Seronegative villous atrophy of the small intestine due to olmesartan use was first described in 2012. We present a new case of olmesartan-induced enteropathy and compare it to recent literature. This case might suggest a use of budesonide for treatment.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Budesonida/uso terapêutico , Imidazóis/efeitos adversos , Enteropatias/induzido quimicamente , Enteropatias/tratamento farmacológico , Tetrazóis/efeitos adversos , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Humanos , Hipertensão/tratamento farmacológico
7.
Trials ; 20(1): 389, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31262348

RESUMO

BACKGROUND: Hypertension is an important risk factor for cardiovascular disease, even in the elderly. Fimasartan is a new non-peptide angiotensin II receptor blocker with a selective type I receptor blocking effect. The objective of this study is to confirm the safety and the non-inferiority of the blood pressure-lowering effect of fimasartan compared with those of perindopril, which has been proven safe and effective in elderly patients with hypertension. METHODS: This is a randomized, double-blind, active-controlled, two-parallel group, optional-titration, multicenter, phase 3 study comparing the efficacy and safety of fimasartan and perindopril arginine. The study population consists of individuals 70 years old or older with essential hypertension. The primary outcome will be a change in sitting systolic blood pressure from baseline after the administration of the investigational product for 8 weeks. The secondary outcomes will be a change in sitting diastolic blood pressure from baseline and changes in sitting systolic blood pressure and diastolic blood pressure from baseline after the administration of the investigational product for 4, 16, and 24 weeks. The sample size will be 119 subjects for each group to confer enough power to test for the primary outcome. DISCUSSION: Research to confirm the efficacy and safety of a new medicine compared with those of previously proven anti-hypertensive drugs is beneficial to guide physicians in the selection of therapeutic agents. If it is confirmed that the new drug is not inferior to the existing drug, the drug will be considered as an option in the treatment of hypertension in elderly patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03246555 , registered on July 25, 2017.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Diuréticos/uso terapêutico , Hipertensão Essencial/tratamento farmacológico , Perindopril/uso terapêutico , Pirimidinas/uso terapêutico , Tetrazóis/uso terapêutico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Compostos de Bifenilo/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Diuréticos/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Estudos de Equivalência como Asunto , Hipertensão Essencial/diagnóstico , Hipertensão Essencial/fisiopatologia , Feminino , Humanos , Masculino , Estudos Multicêntricos como Assunto , Perindopril/efeitos adversos , Pirimidinas/efeitos adversos , República da Coreia , Tetrazóis/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
8.
Medicine (Baltimore) ; 98(28): e16093, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305392

RESUMO

BACKGROUND: LCZ696 has been introduced in patients with hypertension in several trials. Here, we performed a meta-analysis to evaluate the effect and safety of LCZ696 in hypertensive patients. METHODS: PubMed, Embase, the Cochrane Library and ClinicalTrials.gov databases were searched to identify the available randomized controlled trials (RCTs) investigating the effect and safety of LCZ696 in hypertension patients. The last search date was October 31, 2018. RESULTS: Nine RCTs with 6765 subjects were finally included, in which 8 trials compared the effect and safety between LCZ696 and angiotensin receptor antagonists (ARBs). Evidences showed LCZ696, compared with ARBs, achieved a better blood pressure control rate (OR 1.24, 95% CI: 1.14-1.35), specifically, LCZ696 were better at reducing systolic blood pressure [WMD -4.11 mmHg, 95% CI: (-5.13, -3.08) mmHg], diastolic blood pressure [WMD -1.79 mmHg, 95% CI: (-2.22, -1.37) mmHg], mean 24-hour ambulatory systolic blood pressure [WMD -3.24 mmHg, 95% CI: (-4.48, -1.99) mmHg] and mean 24-hour ambulatory diastolic blood pressure [WMD -1.25 mmHg, 95% CI: (-1.81, -0.69) mmHg]. There was no difference in the events of adverse events (risk ratio [RR] 1.01, 95% CI: 0.39-1.09), serious adverse events (RR 0.80, 95% CI: 0.52-1.22) and discontinuation of treatment for any adverse events (RR 0.79, 95% CI: 0.56-1.11) between LCZ696 group and ARB/placebo group, except LCZ696 reduced the rate of headaches (RR 0.69, 95% CI: 0.48-0.99) while increased cough (RR 2.12, 95% CI: 1.11-4.04; P = .02; I = 25%). CONCLUSION: Our finding provides evidence that LCZ 696 was more effective than ARB on blood pressure control and was safe enough in patients with hypertension.


Assuntos
Aminobutiratos/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Tetrazóis/uso terapêutico , Aminobutiratos/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Tetrazóis/efeitos adversos
10.
J Stroke Cerebrovasc Dis ; 28(8): 2262-2267, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31178359

RESUMO

BACKGROUND AND PURPOSE: Uncertainty persists over the effects of blood pressure-lowering treatment in acute intracerebral hemorrhage (ICH). We assessed the effects of treatment with candesartan in acute ICH and according to different types of hematoma. METHODS: Post-hoc analysis of the Scandinavian Candesartan Acute Stroke Trial, a randomized- and placebo-controlled, double-masked trial of candesartan in patients with any stroke within the acute phase (<30 hours) and high systolic blood pressure (≥140 mm Hg). We collected baseline computed tomography scans of participants with ICH, and characterized hematoma volume (planimetric approach), location (deep versus lobar or infratentorial), hemisphere side, and presence of intraventricular hemorrhage. The trial's 2 coprimary effect variables were the composite endpoint of vascular death, stroke or myocardial infarction, and functional outcome at 6 months according to the modified Rankin scale. We used Cox, ordinal, and binary logistic regression for analysis and adjusted for key, predefined prognostic variables. RESULTS: Of 274 participants with ICH, computed tomography scans were available in 205 patients (74.8%). There were no significant differences between the candesartan and placebo groups with respect to hematoma volume (median 15.6 mL versus 13.5 mL, P = .96), deep location (77% versus 72%, P = .64), right hemisphere (49% versus 51%, P = .46), and presence of intraventricular hemorrhage (18% versus 11%, P = .22). Candesartan was associated with a significant increase in poor functional outcome in patients with deep hematoma (adjusted common odds ratio 2.27, 95% confidence interval 1.23-4.18, P = .009, P for interaction .015), but there was no differential effect on functional outcome or vascular events in any of the other imaging subgroups. CONCLUSIONS: Candesartan was not associated with any beneficial effect when initiated in the acute phase of ICH, a possible adverse effect on functional outcome in patients with deep hematomas cannot be ruled out by this study alone.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Benzimidazóis/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hemorragia Cerebral/tratamento farmacológico , Hematoma/tratamento farmacológico , Tetrazóis/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Benzimidazóis/efeitos adversos , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/fisiopatologia , Método Duplo-Cego , Feminino , Hematoma/diagnóstico por imagem , Hematoma/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Países Escandinavos e Nórdicos , Tetrazóis/efeitos adversos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
12.
PLoS One ; 14(4): e0214293, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30964905

RESUMO

BACKGROUND: Angiotensin II receptor blockers (ARBs) are recommended for treating patients with hypertension. However, comparative safety and efficacy of ARB use in elderly patients have not been well established. This study was designed to determine the efficacy of fimasartan, an ARB, in hypertensive elderly patients by measuring clinic and home blood pressures (BPs) and evaluating safety compared to nonelderly patients. METHOD: In the K-MetS study, a nationwide prospective observational study of hypertensive patients on fimasartan, elderly patients (60 years and older) who were treated for 1 year with fimasartan were recruited. BP was evaluated in clinic and at home. RESULTS: Of the 6 399 enrolled patients, 2 363 were elderly (46.9% males, mean age 67.3 ± 5.7 years). Fimasartan reduced systolic and diastolic BP (SBP and DBP) in clinic from 144.1 ± 17.3 to 127.7 ± 12.9 mmHg and from 85.1 ± 10.4 to 76.8 ± 8.4 mmHg, respectively, (all p<0.0001) in 1 year. Similar results were found in home BPs. These BP changes were consistent with those in nonelderly patients. However, pulse pressure, a better predictor of cardiovascular events in the elderly, decreased more in elderly than in nonelderly patients by -8.2 ± 0.3 in elderly and -7.0 ± 0.2 mmHg (p<0.0001), respectively, after adjustment for confounding factors. Adverse events were reported in 1.6% of elderly hypertensives, independent of dose, which was consistent with results in nonelderly patients. CONCLUSIONS: Fimasartan resulted in better pulse pressure reduction with similar BP reduction efficacy and safety in hypertensive elderly patients compared with nonelderly patients.


Assuntos
Compostos de Bifenilo/uso terapêutico , Pressão Sanguínea , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Pirimidinas/uso terapêutico , Tetrazóis/uso terapêutico , Idoso , Compostos de Bifenilo/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Monitorização Ambulatorial da Pressão Arterial , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pirimidinas/efeitos adversos , Tetrazóis/efeitos adversos
13.
Dtsch Med Wochenschr ; 144(6): 394-397, 2019 03.
Artigo em Alemão | MEDLINE | ID: mdl-30870870

RESUMO

HISTORY AND CLINICAL FINDINGS: A 72-year-old female presented with a therapy-resistant diarrhea. EXAMINATIONS: In the case of negative stool cultures and inconspicuous radiological imaging, further endoscopic diagnostics were performed. Histological implicated the image of a celiac disease in the duodenum and lymphocytic colitis reaching into the terminal ileum. In the case of negative antibody detection for celiac disease, a medication side effect was considered by differential diagnosis. TREATMENT: When olmesartan was discontinued, she developed a rapid improvement of the symptoms. CONCLUSION AND DIAGNOSIS: For the angiotensin receptor antagonist olmesartan, the occurrence of a sprue-like enteropathy has rarely described. Microscopic colitis is an exception.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Diarreia , Imidazóis/efeitos adversos , Enteropatias , Tetrazóis/efeitos adversos , Idoso , Pressão Sanguínea , Doença Celíaca , Diagnóstico Diferencial , Diarreia/induzido quimicamente , Diarreia/complicações , Duodeno/efeitos dos fármacos , Duodeno/patologia , Feminino , Humanos , Enteropatias/induzido quimicamente , Enteropatias/complicações
14.
Minerva Cardioangiol ; 67(3): 214-222, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30895762

RESUMO

INTRODUCTION: The efficacy and safety of sacubitril/valsartan used as an antihypertensive agent has not yet been completely assessed. Thus, to investigate them in elderly hypertensive patients, a meta-analysis has been performed. EVIDENCE ACQUISITION: The meta-analysis incorporated only randomized controlled trials (RCTs) in which sacubitril/valsartan was compared with a reference drug. The mean reductions in systolic blood pressure (msSBP) and diastolic blood pressure (msDBP) in the sitting position as well as the mean reductions in ambulatory systolic blood pressure (maSBP) and ambulatory diastolic blood pressure (maDBP), were assumed as efficacy endpoints. Adverse events were taken as safety outcomes. EVIDENCE SYNTHESIS: Five RCTs were included for a total of 1513 patients for analysis. In all studies, the comparator drug was an angiotensin receptor blocker (ARB) - valsartan in two cases and olmesartan in the remaining three cases. Compared with ARBs, there was a significant reduction in msSBP (weight mean difference [WMD] -5.41 mmHg, 95% CI: -7.0 to -3.8; P<0.01), msDBP (WMD=-1.22 mmHg, 95% CI: -2.15 to -0.3; P<0.01), maSBP (WMD=-4.58 mmHg, 95% CI: -5.62 to -3.54; P<0.01) and maDBP (WMD=-2.17 mmHg, 95% CI: - 2.78 to -1.56; P<0.01) in elderly hypertensive patients at 12 weeks. CONCLUSIONS: Sacubitril/valsartan may reduce arterial pressure more efficaciously than ARBs in elderly hypertensive patients.


Assuntos
Aminobutiratos/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Tetrazóis/uso terapêutico , Valsartana/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Aminobutiratos/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Combinação de Medicamentos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Tetrazóis/efeitos adversos , Valsartana/efeitos adversos
15.
Curr Drug Saf ; 14(3): 238-241, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30848210

RESUMO

OBJECTIVE: Olmesartan-induced enteropathy consists a syndrome that mimics celiac disease both clinically and histologically. Cases of this entity have sporadically been reported since 2012 and are usually characterized by severe diarrhea and malabsorption, followed by significant weight loss. CASE REPORT: Herein, we report an uncommon case of this syndrome, where weight loss preceded several months the onset of gastrointestinal symptoms. DISCUSSION AND CONCLUSION: Physicians should be aware of unexplained weight loss in patients taking olmesartan, as prompt discontinuation of the drug may prevent the deleterious consequences of malabsorption.


Assuntos
Anti-Hipertensivos/efeitos adversos , Imidazóis/efeitos adversos , Tetrazóis/efeitos adversos , Perda de Peso , Idoso , Diarreia/induzido quimicamente , Feminino , Humanos , Hipertensão/tratamento farmacológico
16.
Cardiology ; 142(1): 4-6, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30852576

RESUMO

The uptake of sacubitril/valsartan since the PARADIGM study confirmed its beneficial effects on outcomes over enalapril in chronic systolic heart failure has inevitably led to potential interactions with co-prescribed medications in real-world patients. We report two cases that raise the possibility of an interaction between sacubitril/valsartan and the class Ib anti-arrhythmic mexiletine resulting in proarrhythmic effects. We discuss the pharmacokinetics of both agents and posit potential mechanistic interactions that suggest caution should be used and careful monitoring for (ventricular) arrhythmias applied in patients receiving sacubitril/valsartan and mexiletine.


Assuntos
Aminobutiratos/efeitos adversos , Antagonistas de Receptores de Angiotensina/efeitos adversos , Arritmias Cardíacas/induzido quimicamente , Mexiletina/efeitos adversos , Tetrazóis/efeitos adversos , Idoso , Aminobutiratos/farmacocinética , Antagonistas de Receptores de Angiotensina/farmacocinética , Interações de Medicamentos , Feminino , Insuficiência Cardíaca Sistólica/tratamento farmacológico , Humanos , Masculino , Mexiletina/farmacocinética , Tetrazóis/farmacocinética
17.
18.
Ann Pathol ; 39(3): 237-240, 2019 Jun.
Artigo em Francês | MEDLINE | ID: mdl-30712983

RESUMO

Olmesartan induced enteropathy was first described in 2012. It is a rare adverse effect of this antihypertensive drug. The clinical presentation commonly includes severe chronic diarrhea leading to weight loss and a variable degree of dehydration. Histological findings are most commonly observed in the duodenum and consist of partial or total villous atrophy, increased intraepithelial lymphocytes and inflammation in the lamina propria. Involvement of gastric and colic mucosa has also been described. We report on the case of a 63-year-old man, treated by olmesartan, who presented with severe chronic diarrhea. Biopsies from different levels of the gastrointestinal tract revealed a pandigestive intraepithelial lymphocytosis.


Assuntos
Diarreia/induzido quimicamente , Gastroenteropatias/induzido quimicamente , Imidazóis/efeitos adversos , Doenças Raras/induzido quimicamente , Tetrazóis/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Doença Crônica , Desidratação/induzido quimicamente , Gastroenteropatias/patologia , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Perda de Peso
19.
Am J Case Rep ; 20: 111-116, 2019 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-30683835

RESUMO

BACKGROUND Olmesartan, an angiotensin receptor blockade class of antihypertensive medication has recently been associated with a seronegative sprue like enteropathy. Patients typically present with diarrhea and weight loss often prompting exhaustive diagnostic workup. Discontinuation of the drug leads to dramatic recovery and hence, physicians need to be aware of olmesartan associated enteropathy (OAE) in order to avoid unnecessary testing. CASE REPORT A 59-year-old Caucasian male was admitted to the hospital with complaints of intractable diarrhea, vomiting and considerable weight loss. Medical history was notable for hypertension being treated with olmesartan. Workup for all potential infectious causes and celiac disease was negative. Eventually, a colonoscopy was performed due to his persistent symptoms and biopsy revealed lymphocytic colitis. An upper endoscopy was also performed, and histopathology of the duodenum revealed total villous blunting. In light of negative serology for celiac disease and after a detailed review of the patient's medications, the possibility of olmesartan induced enteropathy was considered. Olmesartan was stopped and his symptoms resolved. A follow-up endoscopy done a few months later showed normal small bowel mucosa. CONCLUSIONS This case demonstrates the need for a thorough medication review by healthcare providers especially after a full workup for the patient's symptoms has already been performed. It also reiterates that having an awareness of rare side effects of common medications mitigates the need for extensive diagnostic testing.


Assuntos
Anti-Hipertensivos/efeitos adversos , Colite Linfocítica/induzido quimicamente , Diarreia/induzido quimicamente , Imidazóis/efeitos adversos , Tetrazóis/efeitos adversos , Vômito/induzido quimicamente , Perda de Peso , Humanos , Masculino , Pessoa de Meia-Idade
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