RESUMO
BACKGROUND: Acute declines in estimated glomerular filtration rate (eGFR) occur commonly after starting angiotensin-converting enzyme inhibitors. Whether declines in eGFR that occur after simultaneously starting angiotensin-converting enzyme inhibitors with other antihypertensive agents modifies the benefits of these agents on cardiovascular outcomes is unclear. METHODS AND RESULTS: We identified predictors of acute declines in eGFR (>15% over 3 months) during randomization to benazepril plus amlodipine versus benazepril plus hydrochlorothiazide in the ACCOMPLISH (Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension) trial. We then determined the relation between declines in eGFR (treated as a binary variable, ≤15% versus >15% and separately, as a restricted spline variable) and the composite risk of fatal and nonfatal cardiovascular events using Cox proportional hazards models. We included 10 714 participants (median age 68 years [Q1 63, Q3 73]), of whom 1024 reached the trial end point over median follow-up of 2.8 years. Predictors of acute declines in eGFR>15% over 3 months included assignment to hydrochlorothiazide (versus amlodipine) and higher baseline albuminuria. Overall, declines in eGFR ≥15% (versus <15%) were associated with a 26% higher hazard of cardiovascular outcomes (95% CI, 1.07-1.48). In spline-based analysis, risk for cardiovascular outcomes was higher in the hydrochlorothiazide arm at every level of decline in eGFR compared with the same magnitude of eGFR decline in the amlodipine arm. CONCLUSION: Combined use of benazepril and amlodipine remains superior to benazepril and hydrochlorothiazide for cardiovascular outcomes, regardless of the magnitude of the decline in eGFR that occurred with initiation of therapy.
Assuntos
Anlodipino , Inibidores da Enzima Conversora de Angiotensina , Anti-Hipertensivos , Benzazepinas , Quimioterapia Combinada , Taxa de Filtração Glomerular , Hidroclorotiazida , Hipertensão , Humanos , Anlodipino/uso terapêutico , Anlodipino/efeitos adversos , Hidroclorotiazida/uso terapêutico , Hidroclorotiazida/efeitos adversos , Masculino , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Idoso , Pessoa de Meia-Idade , Benzazepinas/uso terapêutico , Benzazepinas/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Hipertensão/diagnóstico , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Resultado do Tratamento , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/epidemiologia , Rim/fisiopatologia , Rim/efeitos dos fármacos , Fatores de Tempo , Fatores de Risco , Medição de Risco , Bloqueadores dos Canais de Cálcio/uso terapêutico , Bloqueadores dos Canais de Cálcio/efeitos adversosRESUMO
OBJECTIVE: Several guidelines do not recommend beta-blocker as the first-line treatment for hypertension because of its inferior efficacy in stroke prevention. Combination therapy with beta-blocker is commonly used for blood pressure control. We compared the clinical outcomes in patients treated with amlodipine plus bisoprolol (A + B), a ß1-selective beta-blocker and amlodipine plus valsartan (A + V). METHODS: A population-based cohort study was performed using data from the Taiwan National Health Insurance Research Database. From 2012 to 2019, newly diagnosed adult hypertensive patients who received initial amlodipine monotherapy and then switched to A + V or A + B were included. The efficacy outcomes included all-cause death, atherosclerotic cardiovascular disease (ASCVD) event (cardiovascular death, myocardial infarction, ischemic stroke, and coronary revascularization), hemorrhagic stroke, and heart failure. Multivariable Cox proportional hazards model was used to evaluate the relationship between outcomes and different treatments. RESULTS: Overall, 4311 patients in A + B group and 10980 patients in A + V group were included. After a mean follow-up of 4.34 ± 1.79 years, the efficacy outcomes were similar between the A + V and A + B groups regarding all-cause death (adjusted hazard ratio [aHR] 0.99, 95% confidence interval [CI] 0.83-1.18), ASCVD event (aHR 0.97, 95% CI 0.84-1.12), and heart failure (aHR 1.06, 95% CI 0.87-1.30). The risk of hemorrhagic stroke was lower in A + B group (aHR 0.70, 95% CI 0.52-0.94). The result was similar when taking death into consideration in competing risk analysis. The safety outcomes were similar between the 2 groups. CONCLUSIONS: There was no difference of all-cause death, ASCVD event, and heart failure in A + B vs. A + V users. But A + B users had a lower risk of hemorrhagic stroke.
Assuntos
Anlodipino , Anti-Hipertensivos , Bisoprolol , Quimioterapia Combinada , Hipertensão , Humanos , Feminino , Masculino , Bisoprolol/administração & dosagem , Bisoprolol/uso terapêutico , Pessoa de Meia-Idade , Anlodipino/administração & dosagem , Anlodipino/uso terapêutico , Anlodipino/efeitos adversos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/complicações , Idoso , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Resultado do Tratamento , Valsartana/administração & dosagem , Valsartana/uso terapêutico , Taiwan/epidemiologia , Adulto , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Estudos de CoortesRESUMO
BACKGROUND: Systolic blood pressure (BP) is a key predictor of cardiovascular events, but patients with peripheral artery disease (PAD) are rarely included in hypertension trials. The VALUE trial (Valsartan Antihypertensive Long-Term Use Evaluation) investigated the long-term effects of valsartan- or amlodipine-based treatments on cardiovascular outcomes in patients with hypertension with a high cardiovascular risk. The aim of this subanalysis was to clarify the relationship between achieved BP on treatment and cardiovascular outcomes in patients with hypertension with PAD. METHODS: Patients were followed for 4 to 6 years, and BP was measured regularly. The primary end point was time to the first major adverse cardiovascular event, including myocardial infarction, stroke, cardiovascular death, and heart failure requiring hospitalization. Statistical analyses were performed using Cox regression, adjusting for various baseline covariates. RESULTS: Of the 13â 803 participants, 1898 (13.8%) had PAD. During a median follow-up of 4.5 years, patients with PAD had a 23% increased risk of major adverse cardiovascular events compared with patients without PAD. Patients with an achieved systolic BP <130 mmâ Hg and 130 to 139 mmâ Hg, compared with those with systolic BP ≥140 mmâ Hg, were associated with a decreased risk of a major adverse cardiovascular event (hazard ratio, 0.65 [95% CI, 0.43-0.97]; P=0.037; 0.85 [95% CI, 0.74-0.97]; P=0.016, respectively). Additionally, systolic BP <130 mmâ Hg was associated with a decreased risk of cardiovascular death (hazard ratio, 0.33 [95% CI, 0.12-0.92]; P=0.034). The incidence of the primary outcome did not differ between antihypertensive treatment regimens (P=0.365). CONCLUSIONS: Our results indicate that more intensive BP control is associated with a reduction in cardiovascular morbidity and mortality in patients with hypertensive PAD.
Assuntos
Anlodipino , Anti-Hipertensivos , Pressão Sanguínea , Hipertensão , Doença Arterial Periférica , Valsartana , Humanos , Masculino , Doença Arterial Periférica/tratamento farmacológico , Doença Arterial Periférica/complicações , Doença Arterial Periférica/fisiopatologia , Doença Arterial Periférica/mortalidade , Feminino , Hipertensão/tratamento farmacológico , Hipertensão/complicações , Hipertensão/fisiopatologia , Idoso , Anti-Hipertensivos/uso terapêutico , Pessoa de Meia-Idade , Valsartana/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Anlodipino/uso terapêutico , Doenças Cardiovasculares/mortalidade , Seguimentos , Resultado do TratamentoRESUMO
PURPOSE: This study aimed to evaluate the efficacy and tolerability of irbesartan (IRB) and amlodipine (AML) combination therapy in patients with essential hypertension whose blood pressure (BP) was not controlled by IRB monotherapy. METHODS: Two multicenter, randomized, double-blind, placebo-controlled, phase III studies were conducted in Korea (the I-DUO 301 study and the I-DUO 302 study). After a 4-week run-in period with either 150 mg IRB (I-DUO 301 study) or 300 mg IRB (I-DUO 302 study), patients with uncontrolled BP (ie, mean sitting systolic BP [MSSBP] ≥140 mmHg to <180 mmHg and mean sitting diastolic BP <110 mmHg) were randomized to the placebo, AML 5 mg, or AML 10 mg group. A total of 428 participants were enrolled in the 2 I-DUO studies. In the I-DUO 301 study, 271 participants were randomized in a 1:1:1 ratio to receive either IRB/AML 150/5 mg, IRB/AML 150/10 mg, or IRB 150 mg/placebo. In the I-DUO 302 study, 157 participants were randomized in a 1:1 ratio to receive IRB/AML 300/5 mg or IRB 300 mg/placebo. The primary endpoint was the change in MSSBP from baseline to week 8. Tolerability was assessed according to the development of treatment-emergent adverse events (TEAEs) and clinically significant changes in physical examination, laboratory tests, pulse, and 12-lead electrocardiography. FINDINGS: In I-DUO 301, the mean (SD) changes of MSSBP at week 8 from baseline were -14.78 (12.35) mmHg, -21.47 (12.78) mmHg, and -8.61 (12.19) mmHg in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively. In I-DUO 302, the mean (SD) changes of MSSBP at week 8 from baseline were -13.30 (12.47) mmHg and -7.19 (15.37) mmHg in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively. In both studies, all combination groups showed a significantly higher reduction in MSSBP than the IRB monotherapy groups (P < 0.001 for both). TEAEs occurred in 10.00%, 10.99%, and 12.22% of participants in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively, in I-DUO 301 and in 6.33% and 10.67% of participants in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively, in I-DUO 302, with no significant between-group differences. Overall, there was one serious adverse event throughout I-DUO study. IMPLICATIONS: The combination of IRB and AML has superior antihypertensive effects compared with IRB alone over an 8-week treatment period, with placebo-like tolerability. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05476354 (I-DUO 301), NCT05475665 (I-DUO 302).
Assuntos
Anlodipino , Anti-Hipertensivos , Pressão Sanguínea , Quimioterapia Combinada , Hipertensão Essencial , Irbesartana , Humanos , Anlodipino/efeitos adversos , Anlodipino/administração & dosagem , Anlodipino/uso terapêutico , Irbesartana/administração & dosagem , Irbesartana/efeitos adversos , Irbesartana/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Método Duplo-Cego , Hipertensão Essencial/tratamento farmacológico , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Idoso , Resultado do Tratamento , Adulto , República da Coreia , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologiaRESUMO
BACKGROUND: Obstructive sleep apnea (OSA) and hypertension are common conditions that may be linked through sympathetic activation and water retention. We hypothesized that diuretics, which reduce the body water content, may be more effective than amlodipine, a blood pressure (BP)-lowering agent implicated with edema, in controlling OSA in patients with hypertension. We also aimed to compare the effects of these treatments on ambulatory blood pressure monitoring (ABPM). METHODS: In a randomized, double-blind clinical trial, we compared the effects of chlorthalidone/amiloride 25/5 mg with amlodipine 10 mg on OSA measured by portable sleep monitor and BP measured by ABPM. The study included participants older than 40 who had moderate OSA (10-40 apneas/hour of sleep) and BP within the systolic range of 140-159 mmHg or diastolic range of 90-99 mmHg. RESULTS: The individuals in the experimental groups were comparable in age, gender, and other relevant characteristics. Neither the combination of diuretics nor amlodipine alone reduced the AHI after 8 weeks of treatment (AHI 26.3 with diuretics and 25.0 with amlodipine. P = 0.713). Both treatments significantly lowered office, 24-h, and nighttime ABP, but the two groups had no significant difference. CONCLUSION: Chlorthalidone associated with amiloride and amlodipine are ineffective in decreasing the frequency of sleep apnea episodes in patients with moderate OSA and hypertension. Both treatments have comparable effects in lowering both office and ambulatory blood pressure. The notion that treatments could offer benefits for both OSA and hypertension remains to be demonstrated. TRIAL REGISTRATION CLINICALTRIALS. GOV IDENTIFIER: NCT01896661.
Assuntos
Amilorida , Anlodipino , Anti-Hipertensivos , Monitorização Ambulatorial da Pressão Arterial , Clortalidona , Hipertensão , Apneia Obstrutiva do Sono , Humanos , Masculino , Feminino , Método Duplo-Cego , Hipertensão/tratamento farmacológico , Hipertensão/complicações , Pessoa de Meia-Idade , Anti-Hipertensivos/uso terapêutico , Clortalidona/uso terapêutico , Anlodipino/uso terapêutico , Apneia Obstrutiva do Sono/tratamento farmacológico , Apneia Obstrutiva do Sono/complicações , Amilorida/uso terapêutico , Diuréticos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Polissonografia/efeitos dos fármacos , IdosoRESUMO
Hypertension is a common disorder of major clinical, public health and economic importance. It affects men and women of all ages, and the prevalence is increasing in most countries. Maintenance of blood pressure below 140/90 mm of Hg is recommended by most of the guideline available around the world. Various classes of drugs are being used in the treatment of hypertension. Losartan potassium and amlodipine are two different antihypertensive agents belonging to two different groups used commonly around the world in treating essential hypertension. Losartan potassium is non-peptide Angiotensin-II receptor antagonist. Amlodipine which is the third generation dihydropyridine group of calcium channel blocker. The aim of the study was to compare the efficacy and safety of amlodipine and losartan for the treatment of essential hypertensive patients (18-75 years). A non-randomized comparative observational study was conducted in the Department of Pharmacology and Therapeutics in collaboration with Department of Medicine, Sylhet, MAG Osmani Medical College, Sylhet, Bangladesh from July 2021 to June 2022. In this study non-randomization was in two groups. Group A received amlodipine 5mg daily at morning and Group B received losartan potassium 50mg daily at night. The study parameters were systolic blood pressure (SBP), diastolic blood pressure (DBP), ankle oedema, serum K+ level. The result of treatment outcome was compared between two groups. After treatment the reduction of SBP was 5.19±2.93mm of Hg versus 3.27±1.34mm of Hg (p<0.001); reduction of DBP was 1.7±0.70 mm of Hg versus 0.68 mm of Hg (p<0.001) and serum K+ level 4.22±0.27mmol/L versus 4.21±0.16mmol/L (p<0.719) in amlodipine and losartan group respectively. Amlodipine is more effective than losartan potassium in respect to treatment of essential hypertension. Regarding adverse events losartan potassium causes angioedema, hyperkalemia, headache, dizziness etc. The study concluded that amlodipine is superior to losartan potassium in treating essential hypertension.
Assuntos
Hipertensão , Mercúrio , Masculino , Humanos , Feminino , Losartan/uso terapêutico , Losartan/farmacologia , Anlodipino/uso terapêutico , Anlodipino/farmacologia , Bangladesh , Centros de Atenção Terciária , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertensão Essencial/tratamento farmacológico , Hipertensão Essencial/induzido quimicamente , Pressão Sanguínea , Resultado do Tratamento , Mercúrio/farmacologia , Mercúrio/uso terapêutico , Método Duplo-CegoRESUMO
PURPOSE: In a prospective open study, with intervention, conducted in Primary Health Care Units by General Practitioners (GPs) in Portugal, the effectiveness of a single pill of candesartan/amlodipine (ARB/amlodipine), as the only anti-hypertension (anti-HTN) medication, in adult patients with uncontrolled HTN (BP > 140/or > 90 mm Hg), either previously being treated with anti-HTN monotherapies (Group I), or combinations with hydrochlorothiazide (HCTZ) (Group II), or not receiving medication at all (Group III), was evaluated across 12-weeks after implementation of the new therapeutic measure. MATERIALS AND METHODS: A total of 118 GPs recruited patients with uncontrolled HTN who met inclusion/exclusion criteria. Participants were assigned, according to severity, one of 3 (morning) fixed combination candesartan/amlodipine dosage (8/5 or 16/5 or 16/10 mg/day) and longitudinally evaluated in 3 visits (v0, v6 and v12 weeks). Office blood pressure was measured in each visit, and control of HTN was defined per guidelines (BP< 140/90 mmHg). RESULTS: Of the 1234 patients approached, 752 (age 61 ± 10 years, 52% women) participated in the study and were assigned to groups according to previous treatment conditions. The 3 groups exhibited a statistically significant increased control of blood pressure after receiving the fixed combination candesartan/amlodipine dosage. The overall proportion of controlled HTN participants increased from 0,8% at v0 to 82% at v12. The mean arterial blood pressure values decreased from SBP= 159.0 (± 13.0) and DBP= 91.1 (± 9.6) at baseline to SBP= 132,1 (± 11.3) and DBP= 77,5 (± 8.8) at 12 weeks (p < 0.01). Results remained consistent when controlling for age and sex. CONCLUSION: In patients with uncontrolled HTN, therapeutic measures in accordance with guidelines, with a fixed combination candesartan/amlodipine, allowed to overall achieve HTN control at 12 weeks in 82% of previously uncontrolled HTN patients, reinforcing the advantages of these strategies in primary clinical practice.
What is the context?Arterial hypertension (HTN) represents the main risk factor for cause of death from cardiovascular disease (CV). Adequate control of hypertension reduces CV risk and significantly prevents CV events and associated morbidity and mortality. This requires patients' adherence and persistence in implemented treatment and the achievement of tension targets that are related to the reduction of CV risk. The latest international recommendations indicate that hypertension control is insufficient in most countries. In Portugal, hypertension control is <43% and a significant number of patients treated do not comply with the recommendations.What is new?In a prospective, interventional, and multicentre study, carried out by General Practitioners (GPs) in Primary Health Care Units across Portugal, the objective was to determine (i) whether the presence of uncontrolled hypertension results from non-compliance with the provisions of the recommendations and the Integrated Care Process (PAI) of the Direção Geral de Saúde (DGS), i.e. inappropriate use of monotherapies or inadequate low doses of combinations of antihypertensives, and (ii) whether the adjustment of hypertension therapies, favouring the schemes provided in the recommendations, allows adequate control of arterial hypertension, in previously uncontrolled patients, when these are closely monitored in a 12-week time period.What is the impact?When the guidelines' therapeutic protocol is followed, as established for each identified group of patients (monotherapy, hydrochlorothiazide, and no medication), results indicate a marked and statistically significant improvements in both SBP and DBP values and hypertension control across time.
Assuntos
Anti-Hipertensivos , Compostos de Bifenilo , Hipertensão , Atenção Primária à Saúde , Humanos , Hipertensão/tratamento farmacológico , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/administração & dosagem , Compostos de Bifenilo/uso terapêutico , Estudos Prospectivos , Portugal , Tetrazóis/uso terapêutico , Tetrazóis/administração & dosagem , Benzimidazóis/uso terapêutico , Anlodipino/uso terapêutico , Anlodipino/administração & dosagem , Guias de Prática Clínica como Assunto , Médicos de Família , Pressão Sanguínea/efeitos dos fármacos , AdultoRESUMO
BACKGROUND: Gastric cancer (GC) remains a leading cause of cancer mortality globally. Synaptotagmin-4 (SYT4), a calcium-sensing synaptic vesicle protein, has been implicated in the oncogenesis of diverse malignancies. PURPOSE: This study delineates the role of SYT4 in modulating clinical outcomes and biological behaviors in GC. METHODS: We evaluated SYT4 expression in GC specimens using bioinformatics analyses and immunohistochemistry. Functional assays included CCK8 proliferation tests, apoptosis assays via flow cytometry, confocal calcium imaging, and xenograft models. Western blotting elucidated MAPK pathway involvement. Additionally, we investigated the impact of the calcium channel blocker amlodipine on cellular dynamics and MAPK pathway activity. RESULTS: SYT4 was higher in GC tissues, and the elevated SYT4 was significantly correlated with adverse prognosis. Both univariate and multivariate analyses confirmed SYT4 as an independent prognostic indicator for GC. Functionally, SYT4 promoted tumorigenesis by fostering cellular proliferation, inhibiting apoptosis, and enhancing intracellular Ca2+ influx, predominantly via MAPK pathway activation. Amlodipine pre-treatment attenuated SYT4-driven cell growth and potentiated apoptosis, corroborated by in vivo xenograft assessments. These effects were attributed to MAPK pathway suppression by amlodipine. CONCLUSION: SYT4 emerges as a potential prognostic biomarker and a pro-oncogenic mediator in GC through a Ca2+-dependent MAPK mechanism. Amlodipine demonstrates significant antitumor effects against SYT4-driven GC, positing its therapeutic promise. This study underscores the imperative of targeting calcium signaling in GC treatment strategies.
Assuntos
Anlodipino , Sinalização do Cálcio , Neoplasias Gástricas , Sinaptotagminas , Humanos , Anlodipino/farmacologia , Anlodipino/uso terapêutico , Cálcio/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Sinaptotagminas/antagonistas & inibidores , Sinaptotagminas/genética , Sinaptotagminas/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologiaRESUMO
New approaches are needed to lower blood pressure (BP) given persistently low control rates. QUARTET USA sought to evaluate the effect of four-drug, quarter-dose BP lowering combination in patients with hypertension. QUARTET USA was a randomized (1:1), double-blinded trial conducted in federally qualified health centers among adults with hypertension. Participants received either a quadpill of candesartan 2 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg or candesartan 8 mg for 12 weeks. If BP was >130/>80 mm Hg at 6 weeks in either arm, then participants received open label add-on amlodipine 5 mg. The primary outcome was mean change in systolic blood pressure (SBP) at 12 weeks, controlling for baseline BP. Secondary outcomes included mean change in diastolic blood pressure (DBP), and safety included serious adverse events, relevant adverse drug effects, and electrolyte abnormalities. Among 62 participants randomized between August 2019-May 2022 (n = 32 intervention, n = 30 control), mean (SD) age was 52 (11.5) years, 45% were female, 73% identified as Hispanic, and 18% identified as Black. Baseline mean (SD) SBP was 138.1 (11.2) mmHg, and baseline mean (SD) DBP was 84.3 (10.5) mmHg. In a modified intention-to-treat analysis, there was no significant difference in SBP (-4.8 mm Hg [95% CI: -10.8, 1.3, p = 0.123] and a -4.9 mmHg (95% CI: -8.6, -1.3, p = 0.009) greater mean DBP change in the intervention arm compared with the control arm at 12 weeks. Adverse events did not differ significantly between arms. The quadpill had a similar SBP and greater DBP lowering effect compared with candesartan 8 mg. Trial registration number: NCT03640312.
Assuntos
Anlodipino , Anti-Hipertensivos , Benzimidazóis , Compostos de Bifenilo , Bisoprolol , Pressão Sanguínea , Hipertensão , Tetrazóis , Humanos , Feminino , Masculino , Hipertensão/tratamento farmacológico , Pessoa de Meia-Idade , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/administração & dosagem , Método Duplo-Cego , Benzimidazóis/uso terapêutico , Benzimidazóis/efeitos adversos , Benzimidazóis/administração & dosagem , Anlodipino/administração & dosagem , Anlodipino/efeitos adversos , Anlodipino/uso terapêutico , Tetrazóis/uso terapêutico , Tetrazóis/efeitos adversos , Tetrazóis/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Idoso , Resultado do Tratamento , Bisoprolol/uso terapêutico , Bisoprolol/administração & dosagem , Indapamida/uso terapêutico , Indapamida/administração & dosagem , Indapamida/efeitos adversos , Adulto , Quimioterapia CombinadaRESUMO
An increase in systemic blood pressure causes bleeding and ischemia owing to peripheral vascular breakdown, leading to various forms of organ damage. The brain, eyes, kidneys, and cardiovascular system are known target organs for hypertension. To our knowledge, no reports in Japan describe, in detail, the types of antihypertensive drugs used to treat hypertension in cats or its underlying causes. Therefore, we aimed to investigate the use of antihypertensive drugs in domestic cats with hypertension in Japan, the causes of hypertension, and the vital prognosis of these patients. In the present survey, we found that amlodipine was used alone (60/80 cats) or concomitantly (20/80 cats) in all cat patients with hypertension in Japan. We also determined that blood pressure measurements were not yet routinely performed on cats at veterinary clinics in Japan. Furthermore, we have new information suggesting that amlodipine administration in cats with hypertension, which lowers systolic arterial pressure levels to within the normal range (<140 mmHg), may have a negative impact on their survival. Routine blood pressure measurements for cats during their regular health checkups can help identify hypertension, and proper interpretation of blood pressure readings can facilitate suitable treatment measures.
Assuntos
Anlodipino , Anti-Hipertensivos , Doenças do Gato , Hipertensão , Animais , Anlodipino/uso terapêutico , Gatos , Hipertensão/veterinária , Hipertensão/tratamento farmacológico , Japão , Doenças do Gato/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Masculino , Feminino , Pressão Sanguínea/efeitos dos fármacosRESUMO
OBJECTIVE: The investigation of the real-world use of the extemporaneous combination of nebivolol and amlodipine (NA-EXC) in adult patients diagnosed with hypertension in Europe. METHODS: Retrospective analysis of data extracted from seven databases of patient medical records and prescriptions from Italy, Germany, France, Hungary, and Poland, to determine the prevalence and incidence of NA-EXC use and to estimate the number of patients potentially eligible for a single-pill combination of the two antihypertensives. Secondary objectives included: the description of the population of NA-EXC users and the assessment of their adherence to treatment based on the proportion of days covered. RESULTS: The use of NA-EXC was found to be common in Europe and ranged between 2.9% to 9.9% of all patients identified in the databases with a prescription of nebivolol and/or amlodipine. The estimated numbers of patients potentially eligible in 2019 for a single-pill combination of nebivolol and amlodipine in Italy and Germany were, respectively, 178,133 and 113,240. Users of NA-EXC were mostly aged 70-79 years, had metabolic disorders and other comorbidities; >70% of them had received ≥2 concomitant medications before starting NA-EXC. Adherence to NA-EXC was defined as high only in 15.6% to 35% of patients. CONCLUSIONS: The extemporaneous combination of nebivolol and amlodipine is commonly prescribed in Europe, however adherence to the therapy is poor. The development of a single-pill combination of nebivolol and amlodipine may improve adherence by reducing the number of pills administered to patients and thus simplifying treatment regimens.
Assuntos
Anlodipino , Anti-Hipertensivos , Hipertensão , Nebivolol , Humanos , Nebivolol/administração & dosagem , Nebivolol/uso terapêutico , Anlodipino/administração & dosagem , Anlodipino/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Europa (Continente) , Estudos Retrospectivos , Combinação de Medicamentos , Adulto , Adesão à Medicação/estatística & dados numéricos , Idoso de 80 Anos ou mais , Quimioterapia CombinadaRESUMO
BACKGROUND: Modern resin hemoadsorption/hemoperfusion for calcium channel blocker overdose is yet to be reported. The characteristics of calcium channel blockers make them unamenable to removal by hemodiafiltration or charcoal hemoperfusion; however, elimination, using styrene bead adsorption in an ex vivo model, has been demonstrated. Its clinical use is described. CASE REPORT: A man in his 20s was admitted with shock into the Intensive Care Unit (ICU) after an overdose of amlodipine and risperidone. Resuscitation and supportive care were administered, but hypotension did not resolve despite the administration of intravenous fluids, infusions of calcium, adrenaline, and hyperinsulinemic-euglycemic therapy. Methylene blue was then administered to maintain the mean arterial pressures. However, the hemodynamic effect did not allow the weaning of the adrenaline. Drug clearance using hemoadsorption/hemoperfusion was attempted using a styrene resin filter (Jafron HA230; Jafron Biomedical Co., Ltd., Guangdong, China). During the two hemoperfusion sessions (6 h duration each, and 18 h apart) the patient had successfully weaned off all supportive measures, with lactate levels returning to normal and was later discharged home. At the end of each session, significant amlodipine concentrations were detected in blood aspirated from both filters, suggesting enhanced clearance. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Our case illustrates a temporal relationship between resin hemoperfusion therapy, resolution of hemodynamic instability, and shock without proving causation. Significant amlodipine elimination was suggested by high concentrations found in blood from the filter. At the same time, shock resolution after initiation of hemoperfusion occurred in less than one elimination half-life of amlodipine.
Assuntos
Overdose de Drogas , Choque , Masculino , Humanos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Resultado do Tratamento , Anlodipino/uso terapêutico , Choque/etiologia , Choque/terapia , Overdose de Drogas/terapia , Epinefrina , EstirenosRESUMO
BACKGROUND: The objective of the PERSONAL-CovidBP (Personalised Electronic Record Supported Optimisation When Alone for Patients With Hypertension: Pilot Study for Remote Medical Management of Hypertension During the COVID-19 Pandemic) trial was to assess the efficacy and safety of smartphone-enabled remote precision dosing of amlodipine to control blood pressure (BP) in participants with primary hypertension during the COVID-19 pandemic. METHODS AND RESULTS: This was an open-label, remote, dose titration trial using daily home self-monitoring of BP, drug dose, and side effects with linked smartphone app and telemonitoring. Participants aged ≥18 years with uncontrolled hypertension (5-7 day baseline mean ≥135 mm Hg systolic BP or ≥85 mm Hg diastolic BP) received personalized amlodipine dose titration using novel (1, 2, 3, 4, 6, 7, 8, 9 mg) and standard (5 and 10 mg) doses daily over 14 weeks. The primary outcome of the trial was mean change in systolic BP from baseline to end of treatment. A total of 205 participants were enrolled and mean BP fell from 142/87 (systolic BP/diastolic BP) to 131/81 mm Hg (a reduction of 11 (95% CI, 10-12)/7 (95% CI, 6-7) mm Hg, P<0.001). The majority of participants achieved BP control on novel doses (84%); of those participants, 35% were controlled by 1 mg daily. The majority (88%) controlled on novel doses had no peripheral edema. Adherence to BP recording and reported adherence to medication was 84% and 94%, respectively. Patient retention was 96% (196/205). Treatment was well tolerated with no withdrawals from adverse events. CONCLUSIONS: Personalized dose titration with amlodipine was safe, well tolerated, and efficacious in treating primary hypertension. The majority of participants achieved BP control on novel doses, and with personalization of dose there were no trial discontinuations due to drug intolerance. App-assisted remote clinician dose titration may better balance BP control and adverse effects and help optimize long-term care. REGISTRATION: URL: clinicaltrials.gov. Identifier: NCT04559074.
Assuntos
COVID-19 , Hipertensão , Adolescente , Adulto , Humanos , Anlodipino/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Hipertensão Essencial/tratamento farmacológico , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/induzido quimicamente , Pandemias , Projetos Piloto , Smartphone , Resultado do TratamentoRESUMO
In this cohort study, we determined time to blood pressure (BP) control and its predictors among hypertensive PLHIV enrolled in integrated hypertension-HIV care based on the World Health Organization (WHO) HEARTS strategy at Mulago Immunosuppression Clinic in Uganda. From August 2019 to March 2020, we enrolled hypertensive PLHIV aged ≥ 18 years and initiated Amlodipine 5 mg mono-therapy for BP (140-159)/(90-99) mmHg or Amlodipine 5 mg/Valsartan 80 mg duo-therapy for BP ≥ 160/90 mmHg. Patients were followed with a treatment escalation plan until BP control, defined as BP < 140/90 mmHg. We used Cox proportional hazards models to identify predictors of time to BP control. Of 877 PLHIV enrolled (mean age 50.4 years, 62.1% female), 30% received mono-therapy and 70% received duo-therapy. In the monotherapy group, 66%, 88% and 96% attained BP control in the first, second and third months, respectively. For patients on duo-therapy, 56%, 83%, 88% and 90% achieved BP control in the first, second, third, and fourth months, respectively. In adjusted Cox proportional hazard analysis, higher systolic BP (aHR 0.995, 95% CI 0.989-0.999) and baseline ART tenofovir/lamivudine/efavirenz (aHR 0.764, 95% CI 0.637-0.917) were associated with longer time to BP control, while being on ART for >10 years was associated with a shorter time to BP control (aHR 1.456, 95% CI 1.126-1.883). The WHO HEARTS strategy was effective at achieving timely BP control among PLHIV. Additionally, monotherapy anti-hypertensive treatment for stage I hypertension is a viable option to achieve BP control and limit pill burden in resource limited HIV care settings.
Assuntos
Anti-Hipertensivos , Pressão Sanguínea , Infecções por HIV , Hipertensão , Humanos , Feminino , Masculino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Hipertensão/diagnóstico , Pessoa de Meia-Idade , Uganda/epidemiologia , Anti-Hipertensivos/uso terapêutico , Adulto , Pressão Sanguínea/efeitos dos fármacos , Resultado do Tratamento , Fatores de Tempo , Anlodipino/uso terapêuticoRESUMO
BACKGROUND: L-type calcium channels are the only protein channels sensitive to calcium channel blockers, and are expressed in various cancer types. The Cancer Genome Atlas database shows that the mRNA levels of multiple L-type calcium channel subunits in esophageal squamous cell carcinoma tumor tissue are significantly higher than those in normal esophageal epithelial tissue. Therefore, we hypothesized that amlodipine, a long-acting dihydropyridine L-type calcium channel blocker, may inhibit the occurrence and development of esophageal cancer (EC). AIM: To investigate the inhibitory effects of amlodipine on EC through endoplasmic reticulum (ER) stress. METHODS: Cav1.3 protein expression levels in 50 pairs of EC tissues and corresponding paracancerous tissues were examined. Subsequently, the inhibitory effects of amlodipine on proliferation and migration of EC cells in vitro were detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and Transwell assays. In vivo experiments were performed using murine xenograft model. To elucidate the underlying mechanisms, in vitro cell studies were performed to confirm that ER stress plays a role in inhibition proliferation and migration of EC cells treated with amlodipine. RESULTS: The expression level of Cav1.3 in esophageal carcinoma was 1.6 times higher than that in paracancerous tissues. Amlodipine treatment decreased the viability of esophageal carcinoma cells in a dose- and time-dependent manner. In vivo animal experiments also clearly indicated that amlodipine inhibited the growth of EC tumors in mice. Additionally, amlodipine reduces the migration of tumor cells by inhibiting epithelial-mesenchymal transition (EMT). Mechanistic studies have demonstrated that amlodipine induces ER stress-mediated apoptosis and suppresses EMT. Moreover, amlodipine-induced autophagy was characterized by an increase in autophagy lysosomes and the accumulation of light chain 3B protein. The combination of amlodipine with the ER stress inhibitor 4-phenylbutyric acid further confirmed the role of the ER stress response in amlodipine-induced apoptosis, EMT, and autophagy. Furthermore, blocking autophagy increases the ratio of apoptosis and migration. CONCLUSION: Collectively, we demonstrate for the first time that amlodipine promotes apoptosis, induces autophagy, and inhibits migration through ER stress, thereby exerting anti-tumor effects in EC.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Camundongos , Animais , Anlodipino/farmacologia , Anlodipino/uso terapêutico , Neoplasias Esofágicas/patologia , Apoptose , Proliferação de Células , Estresse do Retículo Endoplasmático , Linhagem Celular TumoralRESUMO
BACKGROUND: We investigated seasonal variation in ambulatory blood pressure control in hypertensive patients on clinic blood pressure-guided antihypertensive treatment. METHODS: The study participants were hypertensive patients enrolled in an 8-week therapeutic study. Antihypertensive treatment was initiated with long-acting dihydropyridine calcium channel blockers amlodipine 5âmg/day or the gastrointestinal therapeutic system (GITS) formulation of nifedipine 30âmg/day, with the possible up-titration to amlodipine 10âmg/day or nifedipine-GITS 60âmg/day at 4âweeks of follow-up. RESULTS: The proportion of up-titration to higher dosages of antihypertensive drugs at 4âweeks of follow-up was higher in patients who commenced treatment in autumn/winter ( n â=â302) than those who commenced treatment in spring/summer ( n â=â199, 24.5 vs. 12.0%, P â<â0.001). The control rate of clinic blood pressure, however, was lower in autumn/winter than in spring/summer at 4 (56.7 vs. 70.7%, P â=â0.003) and 8âweeks of follow-up (52.5 vs. 74.9%, P â<â0.001). At 8âweeks, patients who commenced treatment in autumn/winter, compared with those who commenced treatment in spring/summer, had a significantly ( P ≤0.03) smaller daytime (mean between-season difference -3.2/-2.8âmmHg) but greater nighttime SBP/DBP reduction (3.6/1.6âmmHg). Accordingly, at 8âweeks, the prevalence of nondippers was significantly ( P â<â0.001) higher in spring/summer than in autumn/winter for both SBP (54.8 vs. 30.0%) and DBP (53.4 vs. 28.8%). CONCLUSION: Clinic blood pressure-guided antihypertensive treatment requires a higher dosage of medication in cold than warm seasons, which may have led to over- and under-treatment of nighttime blood pressure, respectively.
Assuntos
Anti-Hipertensivos , Hipertensão , Humanos , Nifedipino/uso terapêutico , Nifedipino/efeitos adversos , Estações do Ano , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Anlodipino/uso terapêuticoRESUMO
BACKGROUND AND AIMS: Visit-to-visit systolic blood pressure variability (BPV) is an important predictor of cardiovascular (CV) outcomes. The long-term effect of a period of blood pressure (BP) control, but with differential BPV, is uncertain. Morbidity and mortality follow-up of UK participants in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure-Lowering Arm has been extended for up to 21 years to determine the CV impact of mean systolic blood pressure (SBP) control and BPV during the trial, and amongst those allocated to amlodipine- and atenolol-based treatment. METHODS: Eight thousand five hundred and eighty hypertensive participants (4305 assigned to amlodipine ± perindopril-based and 4275 to atenolol ± diuretic-based treatment during the in-trial period (median 5.5 years) were followed for up to 21 years (median 17.4 years), using linked hospital and mortality records. A subgroup of participants (n = 2156) was followed up 6 years after the trial closure with a self-administered questionnaire and a clinic visit. In-trial mean SBP and standard deviation of visit-to-visit SBP as a measure of BPV, were measured using >100 000 BP measurements. Cox proportional hazard models were used to estimate the risk [hazard ratios (HRs)], associated with (i) mean with SBP and BPV during the in-trial period, for the CV endpoints occurring after the end of the trial and (ii) randomly assigned treatment to events following randomization, for the first occurrence of pre-specified CV outcomes. RESULTS: Using BP data from the in-trial period, in the post-trial period, although mean SBP was a predictor of CV outcomes {HR per 10â mmHg, 1.14 [95% confidence interval (CI) 1.10-1.17], P < .001}, systolic BPV independent of mean SBP was a strong predictor of CV events [HR per 5â mmHg 1.22 (95% CI 1.18-1.26), P < .001] and predicted events even in participants with well-controlled BP. During 21-year follow-up, those on amlodipine-based compared with atenolol-based in-trial treatment had significantly reduced risk of stroke [HR 0.82 (95% CI 0.72-0.93), P = .003], total CV events [HR 0.93 (95% CI 0.88-0.98), P = .008], total coronary events [HR 0.92 (95% CI 0.86-0.99), P = .024], and atrial fibrillation [HR 0.91 (95% CI 0.83-0.99), P = .030], with weaker evidence of a difference in CV mortality [HR 0.91 (95% CI 0.82-1.01), P = .073]. There was no significant difference in the incidence of non-fatal myocardial infarction and fatal coronary heart disease, heart failure, and all-cause mortality. CONCLUSIONS: Systolic BPV is a strong predictor of CV outcome, even in those with controlled SBP. The long-term benefits of amlodipine-based treatment compared with atenolol-based treatment in reducing CV events appear to be primarily mediated by an effect on systolic BPV during the trial period.
Assuntos
Atenolol , Hipertensão , Humanos , Pressão Sanguínea/fisiologia , Atenolol/uso terapêutico , Atenolol/farmacologia , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/farmacologia , Hipertensão/complicações , Anlodipino/uso terapêutico , Fatores de RiscoRESUMO
BACKGROUND: Angina with nonobstructive coronary arteries is a common condition for which no effective treatment has been established. We hypothesized that the measurement of coronary flow reserve (CFR) allows identification of patients with angina with nonobstructive coronary arteries who would benefit from anti-ischemic therapy. METHODS: Patients with angina with nonobstructive coronary arteries underwent blinded invasive CFR measurement and were randomly assigned to receive 4 weeks of amlodipine or ranolazine. After a 1-week washout, they crossed over to the other drug for 4 weeks; final assessment was after the cessation of study medication for another 4 weeks. The primary outcome was change in treadmill exercise time, and the secondary outcome was change in Seattle Angina Questionnaire summary score in response to anti-ischemic therapy. Analysis was on a per protocol basis according to the following classification: coronary microvascular disease (CMD group) if CFR<2.5 and reference group if CFR≥2.5. The study protocol was registered before the first patient was enrolled (International Standard Randomised Controlled Trial Number: ISRCTN94728379). RESULTS: Eighty-seven patients (61±8 years of age; 62% women) underwent random assignment (57 CMD group and 30 reference group). Baseline exercise time and Seattle Angina Questionnaire summary scores were similar between groups. The CMD group had a greater increment (delta) in exercise time than the reference group in response to both amlodipine (difference in delta, 82 s [95% CI, 37-126 s]; P<0.001) and ranolazine (difference in delta, 68 s [95% CI, 21-115 s]; P=0.005). The CMD group reported a greater increment (delta) in Seattle Angina Questionnaire summary score than the reference group in response to ranolazine (difference in delta, 7 points [95% CI, 0-15]; P=0.048), but not to amlodipine (difference in delta, 2 points [95% CI, -5 to 8]; P=0.549). CONCLUSIONS: Among phenotypically similar patients with angina with nonobstructive coronary arteries, only those with an impaired CFR derive benefit from anti-ischemic therapy. These findings support measurement of CFR to diagnose and guide management of this otherwise heterogeneous patient group.
Assuntos
Doença da Artéria Coronariana , Angina Microvascular , Isquemia Miocárdica , Feminino , Humanos , Masculino , Anlodipino/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Circulação Coronária , Estudos Cross-Over , Microcirculação , Fenótipo , Ranolazina/uso terapêutico , Pessoa de Meia-Idade , IdosoRESUMO
OBJECTIVES: This analysis compared adherence, cardiovascular (CV) events and all-cause mortality incidence, and healthcare costs among hypertensive patients treated with perindopril (PER)/indapamide (IND)/amlodipine (AML) in single-pill combination (SPC) vs. multiple-pill combination, in a real-world setting in Italy. METHODS: In this observational retrospective analysis of Italian administrative databases, adult patients treated with PER/IND/AML between 2010 and 2020 were divided into two cohorts: single-pill vs. multiple-pill. Patient data were available for at least one year before and after index date. Propensity score matching (PSM) was applied to reduce selection bias. Adherence was defined as proportion of days covered: non-adherence, <40%; partial adherence, 40-79%, and adherence ≥80%. Mortality incidence and CV events as single, or composite, endpoints were evaluated after first year of follow-up. Healthcare cost analyses were performed from the perspective of the Italian National Health Service. RESULTS: Following PSM, the single-pill cohort included 12 150 patients, and the multiple-pill cohort, 6105. The SPC cohort had a significantly higher percentage of adherent patients vs. the multiple-pill cohort (59.9% vs. 26.9%, P â<â0.001). Following the first year of follow-up, incidence of all-cause mortality, and combined endpoint of all-cause mortality and CV events were lower in the SPC cohort compared with multiple-pill cohort. Average annual direct healthcare costs were lower in the single-pill cohort (2970) vs. multiple-pill cohort (3642); cost of all drugs and all-cause hospitalizations were major contributors. CONCLUSION: The SPC of PER/IND/AML, compared with multiple-pill combination, is associated with higher adherence to medication, lower incidence of CV events and mortality, and reduced healthcare costs.