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1.
Medicine (Baltimore) ; 99(17): e19902, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32332668

RESUMEN

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a disease caused by the infiltration of blood into the subarachnoid space due to the rupture of an intracranial aneurysm. It is a serious cerebrovascular disease, with a mortality rate of about 40% worldwide, which seriously threatens human life and health. Many drugs are used to treat aSAH and its complications, and some have been tested in systematic reviews and have shown good effects. But which drug has the best effect remains unclear. This network meta-analysis (NMA) aims to assess the effectiveness and feasibility of clazosentan, cilostazol, and statins in patients with aSAH. METHODS: We will search for EMBASE.com, PubMed, the Cochrane Library, and Web of Science from inception to December 2019. Randomized controlled trials (RCTs) reporting efficacy and safety of clazosentan, cilostazol, and statins compared with the control, or compared with each other for the treatment of aSAH will be included. Two independent reviewers will assess the risk of bias of the included RCTs with the Cochrane "Risk of bias" tool. The pairwise meta-analysis will be performed with the random-effects model. The NMA will be performed in a Bayesian hierarchical framework using Markov Chain Monte Carlo method in WinBUGS 1.4.3. Egger test and funnel plot will be used to assess the publication bias. We will evaluate the quality of evidence for each outcome according to the GRADE approach. RESULTS: The results of this NMA will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study will summarize up-to-date evidence to compare the efficacy and safety of clazosentan, cilostazol, and statins on aSAH.PROSPERO registration number: CRD42019147523.


Asunto(s)
Protocolos Clínicos , Hemorragia Subaracnoidea/tratamiento farmacológico , Cilostazol/uso terapéutico , Dioxanos/uso terapéutico , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Metaanálisis como Asunto , Piridinas/uso terapéutico , Pirimidinas/uso terapéutico , Literatura de Revisión como Asunto , Hemorragia Subaracnoidea/fisiopatología , Sulfonamidas/uso terapéutico , Tetrazoles/uso terapéutico
2.
Vasc Health Risk Manag ; 16: 41-51, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32021227

RESUMEN

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.


Asunto(s)
Aminobutiratos/uso terapéutico , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Inhibidores de Proteasas/uso terapéutico , Tetrazoles/uso terapéutico , Aminobutiratos/efectos adversos , Bloqueadores del Receptor Tipo 1 de Angiotensina II/efectos adversos , Ensayos Clínicos como Asunto , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Humanos , Neprilisina/antagonistas & inhibidores , Inhibidores de Proteasas/efectos adversos , Factores de Riesgo , Tetrazoles/efectos adversos , Factores de Tiempo , Resultado del Tratamiento
4.
Medicine (Baltimore) ; 98(47): e17978, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31764806

RESUMEN

RATIONALE: Marfan syndrome is a rare cause of heart failure due to primary or secondary cardiomyopathy. Recently, sacubitril/valsartan-an angiotensin receptor blocker-neprilysin inhibitor-has been added in clinical practice as a standard therapy for heart failure. To our knowledge, there are no data on sacubitril/valsartan's effects on cardiovascular outcomes in patients with Marfan syndrome. PATIENT CONCERNS: A 24-year-old man was admitted to our Internal Medicine Department due to dyspnea, ascites, and leg swelling. Arterial blood gas analysis revealed severe hypoxemia with respiratory and metabolic alkalosis. Hilar congestion was highlighted on chest x-ray. DIAGNOSES: Recurrent acute decompensated heart failure with reduced ejection fraction despite optimal medical therapy in Marfan-related cardiomyopathy. INTERVENTIONS AND OUTCOMES: Sacubitril/valsartan was added to optimal medical therapy after hemodynamic stabilization allowing progressive clinical, laboratoristic, and echocardiographic improvement. Patient maintained a free survival from heart failure and a good quality of life until 9-month follow-up. LESSONS: Sacubitril/valsartan should be effective on pathophysiologic mechanisms and cardiovascular outcomes of Marfan syndrome-related cardiovascular complications.


Asunto(s)
Aminobutiratos/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/etiología , Síndrome de Marfan/complicaciones , Tetrazoles/uso terapéutico , Humanos , Masculino , Resultado del Tratamiento , Adulto Joven
5.
Medicine (Baltimore) ; 98(47): e18050, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31764831

RESUMEN

BACKGROUND: This study aims to systematically explore the efficacy of sacubitril valsartan sodium tablet (SVST) for the treatment of chronic heart failure (CHF). METHODS: Nine electronic databases, including PUBMED, Cochrane Library, EMBASE, PsycINFO, Web of Science, Allied and Complementary Medicine Database, WANGFANG, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure will be searched. Randomized controlled trials on SVST in the treatment of CHF will be collected. The search time limit will be from the establishment of each electronic database until June 1, 2019. Two authors will independently select the literature, carry out the data, and assess the methodological quality. RESULTS: This study will systematically investigate the efficacy and safety of SVST for CHF. The outcomes consist of all-cause mortality, change in body weight, urine output, change in serum sodium; and incidence of any expected and unexpected adverse events. CONCLUSION: The findings of this study will summarize from evidence-based medicine and a scientific basis for the efficacy and safety of SVST in the clinical treatment of CHF. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019138882.


Asunto(s)
Aminobutiratos/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Revisiones Sistemáticas como Asunto , Tetrazoles/uso terapéutico , Enfermedad Crónica , Humanos , Proyectos de Investigación , Comprimidos , Resultado del Tratamiento
7.
Rev Med Suisse ; 15(667): 1882-1886, 2019 Oct 16.
Artículo en Francés | MEDLINE | ID: mdl-31617977

RESUMEN

The association of an angiotensin II receptor antagonist and a neprilysin inhibitor (ARNI or Angiotensin Receptor-Neprilysin Inhibitor) is a new actor in the management of heart failure with reduced left ventricular ejection fraction (LVEF). The PARADIGM-HF trial performed in outpatients with a LVEF ≤ 35-40 % demonstrated that sacubitril-valsartan was superior to enalapril in reducing cardiovascular mortality and heart failure hospitalizations. Precautions in the initiation of sacubitril-valsartan, its use as well as its place in the drug management strategy for chronic heart failure are described in the present review. Additional data in patients hospitalized with reduced LVEF, in patients with LVEF > 45 % as well as the effects on blood pressure, renal or cognitive functions are presented.


Asunto(s)
Antagonistas de Receptores de Angiotensina/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Neprilisina/antagonistas & inhibidores , Aminobutiratos/farmacología , Aminobutiratos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Cognición/efectos de los fármacos , Enalapril/farmacología , Enalapril/uso terapéutico , Insuficiencia Cardíaca/metabolismo , Humanos , Riñón/efectos de los fármacos , Neprilisina/metabolismo , Tetrazoles/farmacología , Tetrazoles/uso terapéutico , Resultado del Tratamiento
8.
Hypertension ; 74(5): 1075-1083, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31495277

RESUMEN

Despite the availability of multiple antihypertensive drugs targeting the different pathways implicated in its pathophysiology, hypertension remains poorly controlled worldwide, and its prevalence is increasing because of the aging of the population and the obesity epidemic. Although nonadherence to treatment contributes to uncontrolled hypertension, it is likely that not all the pathophysiological mechanisms are neutralized by the various classes of antihypertensive treatment currently available, and, the counter-regulatory mechanisms triggered by these treatments may decrease their blood pressure-lowering effect. The development of new antihypertensive drugs acting on new targets, with different modes of action, therefore, remains essential, to improve blood pressure control and reduce the residual burden of cardiovascular risks further. However, the difficulties encountered in the conception, development, costs, and delivery to the market of new classes of antihypertensive agents highlights the hurdles that must be overcome to release and to evaluate their long-term safety and efficacy for hypertension only, especially because of the market pressure of cheap generic drugs. New chemical entities with blood pressure-lowering efficacy are thus being developed more for heart failure or diabetic kidney disease, 2 diseases pathophysiologically associated with hypertension. These include dual angiotensin II receptor-neprilysin inhibitors, soluble guanylate cyclase stimulators, nonsteroidal dihydropyridine-based mineralocorticoid receptor antagonists, as well as sodium-glucose cotransporter 2 inhibitors. However, centrally acting aminopeptidase A inhibitors and endothelin receptor antagonists have a dedicated program of development for hypertension. All these emergent drug classes and their potential use in hypertension are reviewed here.


Asunto(s)
Antihipertensivos/farmacología , Drogas en Investigación/química , Drogas en Investigación/clasificación , Hipertensión/tratamiento farmacológico , Neprilisina/efectos de los fármacos , Aminobutiratos/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/uso terapéutico , Aprobación de Drogas , Sistemas de Liberación de Medicamentos , Femenino , Predicción , Humanos , Hipertensión/diagnóstico , Hipertensión/epidemiología , Masculino , Seguridad del Paciente , Tetrazoles/uso terapéutico
9.
Ther Adv Cardiovasc Dis ; 13: 1753944719868134, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31401939

RESUMEN

Since the launch of the first orally available angiotensin II (AngII) type 1 receptor (AT1R) blocker (ARB) losartan (Cozaar) in the late 1990s, the class of ARBs (or 'sartans', short for Angiotensin-RecepTor-ANtagonistS) quickly expanded to include candesartan, eprosartan, irbesartan, valsartan, telmisartan, and olmesartan. All ARBs have high affinity for the AT1 receptor, expressed in various tissues, including smooth muscle cells, heart, kidney, and brain. Since activation of AT1R, the target of these drugs, leads, among other effects, to vascular smooth muscle cell growth, proliferation and contraction, activation of fibroblasts, cardiac hypertrophy, aldosterone secretion from the adrenal cortex, thirst-fluid intake (hypervolemia), etc., the ARBs are nowadays one of the most useful cardiovascular drug classes used in clinical practice. However, significant differences in their pharmacological and clinical properties exist that may favor use of particular agents over others within the class, and, in fact, two of these drugs, candesartan and valsartan, continuously appear to distinguish themselves from the rest of the 'pack' in recent clinical trials. The reason(s) for the potential superiority of these two agents within the ARB class are currently unclear but under intense investigation. The present short review gives an overview of the clinical properties of the ARBs currently approved by the United States Food and Drug Administration, with a particular focus on candesartan and valsartan and the areas where these two drugs seem to have a therapeutic edge. In the second part of our review, we outline recent data from our laboratory (mainly) on the molecular effects of the ARB drugs on aldosterone production and on circulating aldosterone levels, which may underlie (at least in part) the apparent clinical superiority of candesartan (and valsartan) over most other ARBs currently in clinical use.


Asunto(s)
Aldosterona/sangre , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Bencimidazoles/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Sistema Renina-Angiotensina/efectos de los fármacos , Tetrazoles/uso terapéutico , Valsartán/uso terapéutico , Animales , Biomarcadores/sangre , Regulación hacia Abajo , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Humanos , Recuperación de la Función , Resultado del Tratamiento
10.
Drugs ; 79(14): 1543-1556, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31432436

RESUMEN

New therapeutic strategies aimed to tackle the rising socio-economic burden of heart failure (HF) have become an impelling priority. The new pharmacological class of angiotensin (Ang) receptor-neprilysin inhibitors (ARNI) prompted a real conceptual change in the treatment of HF moving from only the inhibition of the renin-Ang-aldosterone system and sympathetic nervous system to a strategy based on the concomitant pharmacological enhancement of endogenous natriuretic peptides. Sacubitril/valsartan, a first-in-class ARNI, has reduced the primary composite endpoint of cardiovascular death or HF hospitalisation, sudden cardiac death, disease progression and improved quality of life, compared with enalapril, in patients on evidence-based contemporary medical therapy. Our review underlines the increasing body of evidence supporting the efficacy of sacubitril/valsartan, which may be considered a new disease-modifying therapy and, after about 30 years of research, a real step forward in HF pharmacological therapy.


Asunto(s)
Aminobutiratos/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Tetrazoles/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/metabolismo , Humanos , Neprilisina/metabolismo , Receptores de Angiotensina/metabolismo
11.
J Headache Pain ; 20(1): 84, 2019 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-31340760

RESUMEN

OBJECTIVE: To study the efficacy and safety of lasmiditan for acute treatment of migraine in patients using migraine preventive medications. BACKGROUND: While lasmiditan has been proven to be an effective acute treatment for migraine, its effectiveness has not been examined when used concurrently with migraine preventives. METHODS: SAMURAI and SPARTAN were similarly designed, double-blind, phase 3, placebo-controlled studies of patients 18 years or older with 3 to 8 migraine attacks per month. Patients were randomized to treat a migraine attack with oral lasmiditan 50 mg (SPARTAN only), 100 mg, 200 mg, or placebo. Migraine preventives were allowed as long as doses were stable for 3 months prior to screening and were unchanged during the study. Preventive medications with established or probable efficacy, as recommended by the American Academy of Neurology, the American Headache Society, and the European Headache Federation, plus botulinum toxin type A and candesartan, were included. Within the subgroups of patients using and not using preventive therapies, lasmiditan and placebo groups were analyzed for the outcome of pain-free at 2 h and other efficacy outcomes. The subgroups of patients using and not using preventive therapies were compared and interaction p-values were calculated for safety and efficacy outcomes. RESULTS: In these trials, 698 of 3981 patients (17.5%) used migraine preventive treatments. Among patients using preventives, all lasmiditan doses resulted in significantly more patients being pain-free at 2 h, compared to placebo (p < 0.05). Primary efficacy outcome (pain-free at 2 h), key secondary outcome (most bothersome symptom-free at 2 h) and all other efficacy outcomes were not significantly different between patients using or not using migraine preventives (all interaction p-values ≥0.1). Rates of adverse events were similar for patients using and not using preventive medications. CONCLUSIONS: Lasmiditan was more effective than placebo for the acute treatment of migraine in patients concurrently using migraine preventive medications. Lasmiditan efficacy and safety measures were similar for patients using and not using preventive medications. TRIAL REGISTRATION: SAMURAI (NCT02439320) and SPARTAN (NCT02605174). Registered 18 March 2015.


Asunto(s)
Benzamidas/uso terapéutico , Trastornos Migrañosos/tratamiento farmacológico , Trastornos Migrañosos/prevención & control , Piperidinas/uso terapéutico , Piridinas/uso terapéutico , Adulto , Bencimidazoles/uso terapéutico , Toxinas Botulínicas Tipo A/uso terapéutico , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tetrazoles/uso terapéutico , Resultado del Tratamiento
12.
Neurology ; 93(6): e559-e567, 2019 08 06.
Artículo en Inglés | MEDLINE | ID: mdl-31292226

RESUMEN

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.


Asunto(s)
Anticonvulsivantes/uso terapéutico , Carbamatos/uso terapéutico , Clorofenoles/uso terapéutico , Epilepsia Refleja/tratamiento farmacológico , Tetrazoles/uso terapéutico , Adolescente , Adulto , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/farmacocinética , Área Bajo la Curva , Carbamatos/efectos adversos , Carbamatos/farmacocinética , Clorofenoles/efectos adversos , Clorofenoles/farmacocinética , Relación Dosis-Respuesta a Droga , Electroencefalografía , Femenino , Humanos , Masculino , Estimulación Luminosa , Método Simple Ciego , Tetrazoles/efectos adversos , Tetrazoles/farmacocinética , Adulto Joven
13.
Trials ; 20(1): 389, 2019 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-31262348

RESUMEN

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.


Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/uso terapéutico , Compuestos de Bifenilo/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Diuréticos/uso terapéutico , Hipertensión Esencial/tratamiento farmacológico , Perindopril/uso terapéutico , Pirimidinas/uso terapéutico , Tetrazoles/uso terapéutico , Factores de Edad , Anciano , Anciano de 80 o más Años , Bloqueadores del Receptor Tipo 1 de Angiotensina II/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antihipertensivos/efectos adversos , Compuestos de Bifenilo/efectos adversos , Ensayos Clínicos Fase III como Asunto , Diuréticos/efectos adversos , Método Doble Ciego , Quimioterapia Combinada , Estudios de Equivalencia como Asunto , Hipertensión Esencial/diagnóstico , Hipertensión Esencial/fisiopatología , Femenino , Humanos , Masculino , Estudios Multicéntricos como Asunto , Perindopril/efectos adversos , Pirimidinas/efectos adversos , República de Corea , Tetrazoles/efectos adversos , Factores de Tiempo , Resultado del Tratamiento
14.
Medicine (Baltimore) ; 98(28): e16093, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31305392

RESUMEN

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.


Asunto(s)
Aminobutiratos/uso terapéutico , Antihipertensivos/uso terapéutico , Hipertensión/tratamiento farmacológico , Tetrazoles/uso terapéutico , Aminobutiratos/efectos adversos , Antihipertensivos/efectos adversos , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Tetrazoles/efectos adversos
16.
J Stroke Cerebrovasc Dis ; 28(8): 2262-2267, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31178359

RESUMEN

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.


Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Antihipertensivos/uso terapéutico , Bencimidazoles/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Hemorragia Cerebral/tratamiento farmacológico , Hematoma/tratamiento farmacológico , Tetrazoles/uso terapéutico , Anciano , Anciano de 80 o más Años , Bloqueadores del Receptor Tipo 1 de Angiotensina II/efectos adversos , Antihipertensivos/efectos adversos , Bencimidazoles/efectos adversos , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/fisiopatología , Método Doble Ciego , Femenino , Hematoma/diagnóstico por imagen , Hematoma/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Países Escandinavos y Nórdicos , Tetrazoles/efectos adversos , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
18.
Biomed Pharmacother ; 116: 109040, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31170664

RESUMEN

Intestinal pathophysiological alterations have recently been revealed to be implicated in the pathogenesis of hypertension, necessitating further investigations to better understand the intestinal effects of anti-hypertensive drugs. The current study thus investigated the pharmacological implications of a commonly used first-line angiotensin II type 1 receptor blocker, candesartan cilexetil, on the intestinal barrier impairment and gut dysbiosis in spontaneously hypertensive rats (SHRs). The results revealed that candesartan treatment protected against ileal and colonic pathologies and increased the intestinal expression of genes encoding tight junction proteins such as cingulin, occludin and tight junction protein 1 in SHRs. Serum level of lipopolysaccharides-binding protein was increased in candesartan-treated SHRs, supporting the notion that candesartan treatment provided protection against hypertension-associated impairment of intestinal barrier. Candesartan treatment also increased the amount of fecal short-chain fatty acids (SCFAs) including acetic acid, propionic acid, and butyric acid in SHRs. Fecal 16S rDNA sequencing further revealed that candesartan treatment normalized hypertension-altered ratio of Firmicutes to Bacteroidetes in SHRs. Most notably, candesartan treatment counteracted hypertension-associated diminishment of lactic acid-producing genus Lactobacillus. Taken together, the current study demonstrates for the first time that candesartan treatment alleviates hypertension-associated pathophysiological alterations in the gut, increases microbial production of SCFAs and preserves gut Lactobacillus under hypertensive conditions, which sheds novel light on the pharmacological implications of candesartan in the treatment of hypertension.


Asunto(s)
Bencimidazoles/uso terapéutico , Tracto Gastrointestinal/fisiopatología , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Tetrazoles/uso terapéutico , Animales , Bencimidazoles/farmacología , Presión Sanguínea/efectos de los fármacos , Colon/efectos de los fármacos , Colon/patología , Colon/fisiopatología , Ácidos Grasos/metabolismo , Heces/química , Fibrosis , Tracto Gastrointestinal/efectos de los fármacos , Tracto Gastrointestinal/microbiología , Íleon/efectos de los fármacos , Íleon/patología , Íleon/fisiopatología , Lactobacillus/efectos de los fármacos , Masculino , Permeabilidad , Ratas Endogámicas SHR , Tetrazoles/farmacología
19.
World J Pediatr Congenit Heart Surg ; 10(3): 292-295, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-31084317

RESUMEN

BACKGROUND: Heart failure (HF) is the leading cause of hospitalizations and death in patients with adult congenital heart disease (ACHD). Sacubitril/valsartan is a new agent in the treatment of HF, but its effects have not been assessed in ACHD. METHODS: We retrospectively studied all 15 patients with ACHD at our center who were prescribed sacubitril/valsartan between June 2017 and June 2018. We assessed baseline characteristics and clinical and laboratory changes after initiation of sacubitril/valsartan. Adverse events, including renal function, medication intolerance, and worsening HF were documented. RESULTS: The median age was 53.2 (27.6-83.6) years, with a median follow-up duration of 69 (8-419) days. At baseline, all patients had refractory HF despite guideline-directed medical therapy, with ten (67%) patients as New York Heart Association (NYHA) class II, and five (33%) patients NYHA class III. The medication was discontinued in one (7%) patient secondary to worsening kidney function. No patients reported clinical deterioration; four NYHA class III patients with complex CHD, pulmonary hypertension, and cyanosis reported significant improvement to NYHA class II. Baseline creatinine was 1.1 (0.9-1.7) and two weeks after starting sacubitril/valsartan it was 1.3 (0.8-2.5, P = .22). CONCLUSIONS: Sacubitril/valsartan seems to be well tolerated in patients with ACHD who present with refractory HF symptoms. Patients with complex CHD associated with cyanosis and pulmonary hypertension could benefit the most, but larger studies are needed to assess the safety as well as the effectiveness of sacubitril/valsartan in this patient population.


Asunto(s)
Aminobutiratos/uso terapéutico , Cardiopatías Congénitas/tratamiento farmacológico , Insuficiencia Cardíaca/tratamiento farmacológico , Volumen Sistólico/fisiología , Tetrazoles/uso terapéutico , Valsartán/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Femenino , Estudios de Seguimiento , Cardiopatías Congénitas/complicaciones , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/etiología , Humanos , Masculino , Persona de Mediana Edad , Neprilisina , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento
20.
World Neurosurg ; 128: e639-e648, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31054336

RESUMEN

BACKGROUND: Clazosentan, an endothelin-1 receptor antagonist, has been shown to prevent the development of large vessel angiographic vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). It has been hypothesized that clazosentan can also reverse established angiographic vasospasm. METHODS: The REVERSE (resynchronization reverses remodeling in systolic left ventricular dysfunction) study was a prospective, multicenter, open-label, 2-stage pilot study of adult patients with aSAH who had received intravenous clazosentan (15 mg/hour) after developing moderate-to-severe angiographic vasospasm. The primary efficacy endpoint was the reversal of global cerebral vasospasm in large cerebral artery segments 3 hours after clazosentan initiation. The secondary endpoints included large artery vasospasm reversal at 24 hours and the maximum change in the angiographic cerebral circulation time. The change in vasospasm severity in the proximal and distal segments was investigated in an exploratory analysis. RESULTS: The primary efficacy endpoint was met in 3 of 11 evaluable patients (27.3%; 95% confidence interval, 6.0-61.0). However, recruitment was stopped after stage 1 in accordance with the predefined interim analysis criteria. In the exploratory analysis, 50.0% and 77.8% of the patients showed a significant reversal of vasospasm or improvement to the admission state in ≥2 distal segments at 3 and 24 hours and 28.6% and 77.8% in ≥2 proximal segments, respectively. CONCLUSIONS: Although the main analysis showed a reversal of large vessel vasospasm 3 hours after clazosentan initiation in a few patients, the exploratory analysis indicated a clear pharmacodynamic dilating effect on vasospastic cerebral vessels at 24 hours in most patients, in particular, in the distal arterial beds. This observation supported the inclusion of patients with established vasospasm in the ongoing REACT (prevention and treatment of vasospasm with clazosentan) trial.


Asunto(s)
Dioxanos/uso terapéutico , Antagonistas de los Receptores de la Endotelina A/uso terapéutico , Piridinas/uso terapéutico , Pirimidinas/uso terapéutico , Hemorragia Subaracnoidea/terapia , Sulfonamidas/uso terapéutico , Tetrazoles/uso terapéutico , Vasoespasmo Intracraneal/tratamiento farmacológico , Adulto , Angiografía de Substracción Digital , Angiografía Cerebral , Embolización Terapéutica , Procedimientos Endovasculares , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos , Proyectos Piloto , Hemorragia Subaracnoidea/complicaciones , Instrumentos Quirúrgicos , Vasoespasmo Intracraneal/etiología , Adulto Joven
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