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1.
Expert Opin Investig Drugs ; 30(10): 1017-1023, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34595995

RESUMO

INTRODUCTION: Resistant hypertension (RH) is more prevalent in the advanced stages of chronic kidney disease (CKD) and contributes to a greater likelihood of poor cardiovascular and renal outcomes. However, RH often goes untreated in this population as the currently available recommended add-on therapy, steroidal mineralocorticoid receptor antagonists (MRAs) such as spironolactone and eplerenone, may lead to unacceptable side effects, mainly hyperkalemia in a cohort with reduced kidney function. KBP-5074 is a novel non-steroidal MRA that addresses the unmet need of treating RH in the CKD population without hyperkalemia. AREAS COVERED: We provide an overview of the current state of RH treatment in stage 3B/4 CKD as it relates to available steroidal MRAs and the current limitations of this treatment. We then explore the emerging data on nonsteroidal MRAs, particularly the novel agent KBP-5074 and its applicability to treatment in this context. EXPERT OPINION: In a randomized, double-blind, placebo-controlled phase 2b trial, the novel nonsteroidal MRA KBP-5074 demonstrated clinical efficacy and safety in treating RH in stage 3B/4 CKD and offers a potential new treatment option in this population at high risk for cardiovascular disease (CVD) and CKD progression.


Assuntos
Hipertensão/tratamento farmacológico , Piperidinas/administração & dosagem , Pirazóis/administração & dosagem , Quinolinas/administração & dosagem , Insuficiência Renal Crônica/tratamento farmacológico , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/farmacologia , Progressão da Doença , Resistência a Medicamentos , Humanos , Hipertensão/etiologia , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Piperidinas/efeitos adversos , Piperidinas/farmacologia , Pirazóis/efeitos adversos , Pirazóis/farmacologia , Quinolinas/efeitos adversos , Quinolinas/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/complicações
2.
Cochrane Database Syst Rev ; 10: CD003654, 2021 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-34657281

RESUMO

BACKGROUND: This is the first update of a review published in 2010. While calcium channel blockers (CCBs) are often recommended as a first-line drug to treat hypertension, the effect of CCBs on the prevention of cardiovascular events, as compared with other antihypertensive drug classes, is still debated. OBJECTIVES: To determine whether CCBs used as first-line therapy for hypertension are different from other classes of antihypertensive drugs in reducing the incidence of major adverse cardiovascular events. SEARCH METHODS: For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials (RCTs) up to 1 September 2020: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2020, Issue 1), Ovid MEDLINE, Ovid Embase, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted the authors of relevant papers regarding further published and unpublished work and checked the references of published studies to identify additional trials. The searches had no language restrictions. SELECTION CRITERIA: Randomised controlled trials comparing first-line CCBs with other antihypertensive classes, with at least 100 randomised hypertensive participants and a follow-up of at least two years. DATA COLLECTION AND ANALYSIS: Three review authors independently selected the included trials, evaluated the risk of bias, and entered the data for analysis. Any disagreements were resolved through discussion. We contacted study authors for additional information. MAIN RESULTS: This update contains five new trials. We included a total of 23 RCTs (18 dihydropyridines, 4 non-dihydropyridines, 1 not specified) with 153,849 participants with hypertension. All-cause mortality was not different between first-line CCBs and any other antihypertensive classes. As compared to diuretics, CCBs probably increased  major cardiovascular events (risk ratio (RR) 1.05, 95% confidence interval (CI) 1.00 to 1.09, P = 0.03) and increased congestive heart failure events (RR 1.37, 95% CI 1.25 to 1.51, moderate-certainty evidence). As compared to beta-blockers, CCBs reduced the following outcomes: major cardiovascular events (RR 0.84, 95% CI 0.77 to 0.92), stroke (RR 0.77, 95% CI 0.67 to 0.88, moderate-certainty evidence), and cardiovascular mortality (RR 0.90, 95% CI 0.81 to 0.99, low-certainty evidence). As compared to angiotensin-converting enzyme (ACE) inhibitors, CCBs reduced stroke (RR 0.90, 95% CI 0.81 to 0.99, low-certainty evidence) and increased congestive heart failure (RR 1.16, 95% CI 1.06 to 1.28, low-certainty evidence). As compared to angiotensin receptor blockers (ARBs), CCBs reduced myocardial infarction (RR 0.82, 95% CI 0.72 to 0.94, moderate-certainty evidence) and increased congestive heart failure (RR 1.20, 95% CI 1.06 to 1.36, low-certainty evidence). AUTHORS' CONCLUSIONS: For the treatment of hypertension, there is moderate certainty evidence that diuretics reduce major cardiovascular events and congestive heart failure more than CCBs. There is low to moderate certainty evidence that CCBs probably reduce major cardiovascular events more than beta-blockers. There is low to moderate certainty evidence that CCBs reduced stroke when compared to angiotensin-converting enzyme (ACE) inhibitors and reduced myocardial infarction when compared to angiotensin receptor blockers (ARBs), but increased congestive heart failure when compared to ACE inhibitors and ARBs. Many of the differences found in the current review are not robust, and further trials might change the conclusions. More well-designed RCTs studying the mortality and morbidity of individuals taking CCBs as compared with other antihypertensive drug classes are needed for patients with different stages of hypertension, different ages, and with different comorbidities such as diabetes.


Assuntos
Hipertensão , Preparações Farmacêuticas , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Humanos , Hipertensão/tratamento farmacológico
3.
BMC Fam Pract ; 22(1): 208, 2021 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-34666689

RESUMO

BACKGROUND: Polypharmacy is defined as the prescription of at least 5 different medicines for therapeutic or prophylactic effect and is a serious issue among elderly patients, who are frequently affected by multi-morbidity. Deprescribing is one of the proposed approaches to reduce the number of administered drugs, by eliminating those that are inappropriately prescribed. The aim of this systematic review is to provide an updated and systematic assessment of the benefit-risk profile of deprescribing of anti-hypertensive drugs, which are among the most commonly used drugs. METHODS: MEDLINE, EMBASE and The Cochrane Library were searched for studies assessing the efficacy and safety of anti-hypertensive drugs deprescribing in the period between January, 12,016 and December, 312,019. The quality of randomized clinical trials (RCTs) was assessed using the GRADE approach for the evaluation of the main outcomes. The risk of bias assessment was carried out using the Cochrane risk-of-bias tool. RESULTS: Overall, two RCTs were identified. Despite summarized evidence was in favor of anti-hypertensive deprescribing, the overall risk of bias was rated as high for each RCT included. According to the GRADE approach, the overall quality of the RCTs included was moderate regarding the following outcomes: systolic blood pressure < 150 mmHg after 12 weeks of follow-up, quality of life, frailty and cardiovascular risk. CONCLUSIONS: This updated systematic review of the efficacy and safety of anti-hypertensive treatment deprescribing found two recently published RCTs, in addition to the previous guideline of the National Institute for Health and Care Excellence (NICE). Evidence points towards non-inferiority of anti-hypertensive deprescribing as compared to treatment continuation, despite the quality of published studies is not high. High quality experimental studies are urgently needed to further assess the effect of deprescribing for this drug class in specific categories of patients.


Assuntos
Anti-Hipertensivos , Desprescrições , Idoso , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea , Humanos , Polimedicação , Qualidade de Vida
5.
Int Heart J ; 62(5): 1076-1082, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34544969

RESUMO

The impact of beta2-agonists (B2As) on heart failure (HF) remains controversial. This study aimed to investigate whether inhaled B2As increased in-hospital mortality in ICU patients with HF.The Multiparameter Intelligent Monitoring in Intensive Care III database was initially searched to identify adult patients (≥ 18 years old) with HF in ICU. Then, patients using or not using inhaled B2As were matched using propensity score matching on a 1:1 basis to control for baseline confounders. In-hospital mortality was compared between the two groups, and logistic regression analysis was performed to assess the association between B2As and in-hospital mortality.The initial search retrieved 2345 eligible patients with HF from the database. After propensity score matching, 705 pairs of patients were included in the final analysis. Patients using B2As had markedly higher in-hospital mortality than those not using B2As (4.68% versus 2.27%; P = 0.013). In the multivariate logistic regression analysis, B2A use (odd ratios (OR), 2.471; 95% confidence interval (CI), 1.289-4.734; P = 0.006), stroke (OR, 4.581; 95% CI, 1.621-12.948; P = 0.004), and simplified acute physiology score II (SAPS-II) scores (OR, 1.090; 95% CI, 1.064-1.116; P < 0.001) were significantly associated with increased risk of in-hospital mortality, whereas renin angiotensin system inhibitor use (OR, 0.396; 95% CI, 0.202-0.778; P = 0.007) was significantly associated with decreased risk of in-hospital mortality. Subgroup analysis further indicated that the association between B2A use and mortality was significant only in patients with HF without chronic pulmonary disease (OR, 2.427; 95% CI, 1.351-4.362; P = 0.003), but not in those with chronic pulmonary disease (OR, 2.094; 95% CI, 0.582-7.537; P = 0.258).In ICU patients with HF but without chronic pulmonary disease, the use of inhaled B2As is associated with increased in-hospital mortality.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Mortalidade Hospitalar/tendências , Unidades de Terapia Intensiva/estatística & dados numéricos , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Estudos de Casos e Controles , Doença Crônica , Feminino , Humanos , Pneumopatias/complicações , Pneumopatias/mortalidade , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Análise de Regressão , Sistema Renina-Angiotensina/efeitos dos fármacos , Estudos Retrospectivos
6.
J Nephrol ; 34(5): 1457-1465, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34487334

RESUMO

BACKGROUND: Additional research is warranted for the clinical significance of post-transplant hypertension and related antihypertensive medication use in kidney transplant (KT) recipients. METHODS: This observational study included nationwide KT recipients who maintained a functioning graft for at least 1 year after KT in South Korea, observed between 2008 and 2017. The use of antihypertensive medications lasting between 6 months and 1 year was the main exposure, and those who had inconsistent/transient use of antihypertensive drugs were excluded. The prognostic outcome included death-censored graft failure (DCGF), death-with functioning graft (DWFG), and major adverse cerebrocardiovascular events (MACCEs). RESULTS: We included 8,014 patients without post-transplant hypertension and 6,114 recipients who received treatment for hypertension in the post-transplant period. Those with post-transplant hypertension had a significantly higher risk of DCGF than those without [adjusted hazard ratio (HR) 1.27 (1.09-1.48)]. Post-transplant hypertension patients who required multiple drugs showed a significantly higher risk of DWFG [HR 1.57 (1.17-2.10)] and MACCE [HR 1.35 (1.01-1.81)] than the controls. Among the single-agent users, those who received beta-blockers showed a significantly higher risk of DCGF, although the risks of DWFG or MACCE were similar between the types of antihypertensive agents. Among the multiple agent users, the prognosis was similar, regardless of the prescribed types of antihypertensive agents. CONCLUSION: Post-transplant hypertension was associated with poor post-transplant prognosis, particularly when multiple types of medications were required for treatment. During initial prescription of antihypertensive medication, clinicians may consider that beta-blockers were associated with a higher risk of DCGF in the single-agent users.


Assuntos
Hipertensão , Transplante de Rim , Anti-Hipertensivos/efeitos adversos , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Transplante de Rim/efeitos adversos , Prognóstico , Fatores de Risco , Transplantados
7.
Rev Med Suisse ; 17(750): 1556-1559, 2021 Sep 15.
Artigo em Francês | MEDLINE | ID: mdl-34528418

RESUMO

Thiazide diuretics (hydrochlorothiazide) and « thiazide-like ¼ (chlorthalidone, indapamide) are widely prescribed due to their effectiveness in the treatment of arterial hypertension. The use of thiazides may be complicated by hyponatremia that is associated with increased morbidity and mortality. The pathophysiology of thiazide-induced hyponatremia is not yet clear. It is currently difficult to predict who will develop thiazide-induced hyponatremia. Genetic predisposition is considered, and several studies are attempting to clarify it in order to identify patients at risk of developing hyponatremia after taking a thiazide. Their reintroduction to a patient who already presented hyponatremia upon thiazide should be avoided.


Assuntos
Hiponatremia , Indapamida , Anti-Hipertensivos/efeitos adversos , Clortalidona/efeitos adversos , Humanos , Hiponatremia/induzido quimicamente , Tiazidas/efeitos adversos
8.
N Engl J Med ; 385(14): 1268-1279, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34491661

RESUMO

BACKGROUND: The appropriate target for systolic blood pressure to reduce cardiovascular risk in older patients with hypertension remains unclear. METHODS: In this multicenter, randomized, controlled trial, we assigned Chinese patients 60 to 80 years of age with hypertension to a systolic blood-pressure target of 110 to less than 130 mm Hg (intensive treatment) or a target of 130 to less than 150 mm Hg (standard treatment). The primary outcome was a composite of stroke, acute coronary syndrome (acute myocardial infarction and hospitalization for unstable angina), acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes. RESULTS: Of the 9624 patients screened for eligibility, 8511 were enrolled in the trial; 4243 were randomly assigned to the intensive-treatment group and 4268 to the standard-treatment group. At 1 year of follow-up, the mean systolic blood pressure was 127.5 mm Hg in the intensive-treatment group and 135.3 mm Hg in the standard-treatment group. During a median follow-up period of 3.34 years, primary-outcome events occurred in 147 patients (3.5%) in the intensive-treatment group, as compared with 196 patients (4.6%) in the standard-treatment group (hazard ratio, 0.74; 95% confidence interval [CI], 0.60 to 0.92; P = 0.007). The results for most of the individual components of the primary outcome also favored intensive treatment: the hazard ratio for stroke was 0.67 (95% CI, 0.47 to 0.97), acute coronary syndrome 0.67 (95% CI, 0.47 to 0.94), acute decompensated heart failure 0.27 (95% CI, 0.08 to 0.98), coronary revascularization 0.69 (95% CI, 0.40 to 1.18), atrial fibrillation 0.96 (95% CI, 0.55 to 1.68), and death from cardiovascular causes 0.72 (95% CI, 0.39 to 1.32). The results for safety and renal outcomes did not differ significantly between the two groups, except for the incidence of hypotension, which was higher in the intensive-treatment group. CONCLUSIONS: In older patients with hypertension, intensive treatment with a systolic blood-pressure target of 110 to less than 130 mm Hg resulted in a lower incidence of cardiovascular events than standard treatment with a target of 130 to less than 150 mm Hg. (Funded by the Chinese Academy of Medical Sciences and others; STEP ClinicalTrials.gov number, NCT03015311.).


Assuntos
Anti-Hipertensivos/administração & dosagem , Hipertensão/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Feminino , Humanos , Hipertensão/complicações , Hipotensão/induzido quimicamente , Incidência , Masculino , Pessoa de Meia-Idade , Padrão de Cuidado , Sístole
9.
PLoS Med ; 18(9): e1003803, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34543267

RESUMO

BACKGROUND: Hypertension treatment reduces morbidity and mortality yet has not been broadly implemented in many low-resource settings, including sub-Saharan Africa (SSA). We hypothesized that a patient-centered integrated chronic disease model that included hypertension treatment and leveraged the HIV care system would reduce mortality among adults with uncontrolled hypertension in rural Kenya and Uganda. METHODS AND FINDINGS: This is a secondary analysis of the SEARCH trial (NCT:01864603), in which 32 communities underwent baseline population-based multidisease testing, including hypertension screening, and were randomized to standard country-guided treatment or to a patient-centered integrated chronic care model including treatment for hypertension, diabetes, and HIV. Patient-centered care included on-site introduction to clinic staff at screening, nursing triage to expedite visits, reduced visit frequency, flexible clinic hours, and a welcoming clinic environment. The analytic population included nonpregnant adults (≥18 years) with baseline uncontrolled hypertension (blood pressure ≥140/90 mm Hg). The primary outcome was 3-year all-cause mortality with comprehensive population-level assessment. Secondary outcomes included hypertension control assessed at a population level at year 3 (defined per country guidelines as at least 1 blood pressure measure <140/90 mm Hg on 3 repeated measures). Between-arm comparisons used cluster-level targeted maximum likelihood estimation. Among 86,078 adults screened at study baseline (June 2013 to July 2014), 10,928 (13%) had uncontrolled hypertension. Median age was 53 years (25th to 75th percentile 40 to 66); 6,058 (55%) were female; 677 (6%) were HIV infected; and 477 (4%) had diabetes mellitus. Overall, 174 participants (3.2%) in the intervention group and 225 participants (4.1%) in the control group died during 3 years of follow-up (adjusted relative risk (aRR) 0.79, 95% confidence interval (CI) 0.64 to 0.97, p = 0.028). Among those with baseline grade 3 hypertension (≥180/110 mm Hg), 22 (4.9%) in the intervention group and 42 (7.9%) in the control group died during 3 years of follow-up (aRR 0.62, 95% CI 0.39 to 0.97, p = 0.038). Estimated population-level hypertension control at year 3 was 53% in intervention and 44% in control communities (aRR 1.22, 95% CI 1.12 to 1.33, p < 0.001). Study limitations include inability to identify specific causes of death and control conditions that exceeded current standard hypertension care. CONCLUSIONS: In this cluster randomized comparison where both arms received population-level hypertension screening, implementation of a patient-centered hypertension care model was associated with a 21% reduction in all-cause mortality and a 22% improvement in hypertension control compared to standard care among adults with baseline uncontrolled hypertension. Patient-centered chronic care programs for HIV can be leveraged to reduce the overall burden of cardiovascular mortality in SSA. TRIAL REGISTRATION: ClinicalTrials.gov NCT01864603.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Serviços de Saúde Comunitária , Prestação Integrada de Cuidados de Saúde , Hipertensão/terapia , Assistência Centrada no Paciente , Adolescente , Adulto , Idoso , Fármacos Anti-HIV/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Causas de Morte , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/mortalidade , Diabetes Mellitus/terapia , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/mortalidade , Infecções por HIV/terapia , Humanos , Hipertensão/diagnóstico , Hipertensão/mortalidade , Hipertensão/fisiopatologia , Hipoglicemiantes/uso terapêutico , Quênia , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Uganda , Adulto Jovem
10.
Jpn J Ophthalmol ; 65(6): 810-819, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34495425

RESUMO

PURPOSE: To assess the long-term safety and efficacy of omidenepag isopropyl (OMDI) 0.002% (a first-in-class, selective, non-prostaglandin, prostanoid EP2 receptor agonist), alone or administered concomitantly with timolol 0.5%, in patients with open-angle glaucoma (OAG, including normal-tension and exfoliation glaucoma) or ocular hypertension (OHT). STUDY DESIGN: Open-label, multicenter, Phase 3 study (NCT02822729). METHODS: Patients aged ≥ 20 years, with OAG or OHT, and a baseline diurnal intraocular pressure (IOP) ≥ 16- < 22 mmHg (Group 1) or ≥ 22- ≤ 34 mmHg (Groups 2 and 3) were enrolled. All patients (N = 125) received OMDI 0.002% once daily. Group 3 also received timolol 0.5% twice daily. IOP was measured at baseline and at Weeks 2, 4, 8, 12, 26, 40, and 52. RESULTS: Significant reductions in mean diurnal IOP from baseline occurred at every visit (P < 0.0001). Mean ± SE diurnal IOP reduction at Week 52 was -3.7 ± 0.3 mmHg (Group 1), -5.6 ± 0.5 mmHg (Group 2), and -8.4 ± 0.6 mmHg (Group 3). Most adverse events (AEs) were mild, and no serious treatment-related AEs were reported. Conjunctival hyperemia (incidence: monotherapy [Groups 1 and 2], 18.8%; concomitant [Group 3], 45.0%) and macular edema (ME)/cystoid macular edema (CME) (incidence: monotherapy, 11.8%; concomitant, 15.0%) occurred most frequently. All treatment-related ME/CME cases occurred in pseudophakic eyes and responded to standard-of-care treatment and study drug discontinuation. CONCLUSIONS: In this study, OMDI 0.002%, alone or administered concomitantly with timolol 0.5%, resulted in sustained IOP reduction over 52 weeks in patients with OAG or OHT. Concomitant treatment resulted in increased efficacy and increased incidence of conjunctival hyperemia.


Assuntos
Glaucoma de Ângulo Aberto , Hipertensão Ocular , Anti-Hipertensivos/efeitos adversos , Método Duplo-Cego , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/tratamento farmacológico , Glicina/análogos & derivados , Humanos , Pressão Intraocular , Hipertensão Ocular/tratamento farmacológico , Soluções Oftálmicas , Pirazóis , Piridinas , Timolol/efeitos adversos , Resultado do Tratamento
11.
Am J Physiol Renal Physiol ; 321(4): F548-F557, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34486399

RESUMO

Chronic kidney disease (CKD) is characterized by the progressive functional loss of nephrons and hypertension (HTN). Some antihypertensive regimens attenuate the progression of CKD (blockers of the renin-angiotensin system). Although studies have suggested that calcium channel blocker (CCB) therapy mitigates the decline in renal function in humans with essential HTN, there are few long-term clinical studies that have determined the impact of CCBs in patients with hypertensive CKD. Dihydropyridine (DHP) or L-type CCBs preferentially vasodilate the afferent arteriole and have been associated with glomerular HTN and increases in proteinuria in animal models with low renal function. Small clinical studies in vulnerable populations with renal disease such as African Americans, children, and diabetics have also suggested that DHP CCBs exacerbate glomerular injury, which questions the renoprotective effect of this class of antihypertensive drug. We used an established integrative mathematical model of human physiology, HumMod, to test the hypothesis that DHP CCB therapy exacerbates pressure-induced glomerular injury in hypertensive CKD. Over a simulation of 3 yr, CCB therapy reduced mean blood pressure by 14-16 mmHg in HTN both with and without CKD. Both impaired tubuloglomerular feedback and low baseline renal function exacerbated glomerular pressure, glomerulosclerosis, and the decline in renal function during L-type CCB treatment. However, simulating CCB therapy that inhibited both L- and T-type calcium channels increased efferent arteriolar vasodilation and alleviated glomerular damage. These simulations support the evidence that DHP (L-type) CCBs potentiate glomerular HTN during CKD and suggest that T/L-type CCBs are valuable in proteinuric renal disease treatment.NEW & NOTEWORTHY Our physiological model replicates clinical trial results and provides unique insights into possible mechanisms that play a role in glomerular injury and hypertensive kidney disease progression during chronic CCB therapy. Specifically, these simulations predict the temporal changes in renal function with CCB treatment and demonstrate important roles for tubuloglomerular feedback and efferent arteriolar conductance in the control of chronic kidney disease progression.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Canais de Cálcio Tipo L/efeitos dos fármacos , Canais de Cálcio Tipo T/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Glomérulos Renais/irrigação sanguínea , Modelos Biológicos , Insuficiência Renal Crônica/tratamento farmacológico , Vasodilatadores/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Canais de Cálcio Tipo L/metabolismo , Canais de Cálcio Tipo T/metabolismo , Simulação por Computador , Humanos , Hipertensão/diagnóstico , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Vasodilatadores/efeitos adversos
13.
Ned Tijdschr Geneeskd ; 1652021 06 17.
Artigo em Holandês | MEDLINE | ID: mdl-34346625

RESUMO

High blood pressure is a common finding in hospitalized patients. Anxiety, pain and fever can all increase blood pressure to various degrees. The question is whether this adaptive response is harmful and should lead to initiation or intensification of treatment or can be ignored. A recent retrospective study has shown that intensification of blood pressure lowering medication in patients who are hospitalized with non-cardiac conditions is associated with a higher incidence of in-hospital complications, in particular myocardial infarction and renal insufficiency, while another study demonstrated that patients who are discharged from hospital with intensified antihypertensive treatment have an increased risk of readmission without a reduction in cardiac events after one year. Although retrospective in nature, these data show that we should be careful with anti-hypertensive medication in patients hospitalized for non-cardiac conditions and that blood pressure monitoring should be focused on the identification of low rather than high blood pressure values.


Assuntos
Hipertensão , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea , Hospitais , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Estudos Retrospectivos
14.
Cancer Causes Control ; 32(12): 1375-1384, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34347212

RESUMO

PURPOSE: Antihypertensives are commonly prescribed medications and their effect on breast cancer recurrence and mortality is not clear, particularly among specific molecular subtypes of breast cancer: luminal, triple-negative (TN), and HER2-overexpressing (H2E). METHODS: A population-based prospective cohort study of women aged 20-69 diagnosed with a first primary invasive breast cancer between 2004 and 2015 was conducted in the Seattle, Washington and Albuquerque, New Mexico greater metropolitan areas. Multivariable-adjusted Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for risks of breast cancer recurrence, breast cancer-specific mortality, and all-cause mortality associated with hypertension and antihypertensives. RESULTS: In this sample of 2,383 luminal, 1,559 TN, and 615 H2E breast cancer patients, overall median age was 52 (interquartile range, 44-60). Hypertension and current use of antihypertensives were associated with increased risks of all-cause mortality in each subtype. Current use of angiotensin-converting enzyme inhibitors was associated with increased risks of both recurrence and breast cancer-specific mortality among luminal patients (HR: 2.5; 95% CI: 1.5, 4.3 and HR: 1.9; 95% CI: 1.2, 3.0, respectively). Among H2E patients, current use of calcium channel blockers was associated with an increased risk of breast cancer-specific mortality (HR: 1.8; 95% CI: 0.6, 5.4). CONCLUSION: Our findings suggest that some antihypertensive medications may be associated with adverse breast cancer outcomes among women with certain molecular subtypes. Additional studies are needed to confirm these findings.


Assuntos
Neoplasias da Mama , Hipertensão , Anti-Hipertensivos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Receptor ErbB-2 , Receptores de Progesterona
15.
BMJ Case Rep ; 14(8)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404652

RESUMO

Hydralazine is a commonly prescribed antihypertensive agent. Some of its labelled adverse reactions include lupus-like syndrome, tachycardia, headache and fever. Despite its well-known side effects, little is known about hydralazine's hepatotoxic effects. We report the case of a 54-year-old female patient who was started on hydralazine for hypertension management but later presented with hydralazine-induced liver injury. Her initial presentation consisted of non-specific symptoms and a hepatocellular injury pattern. Liver biopsy revealed hepatic steatosis. Three weeks after discontinuation of hydralazine, the patient's liver enzymes normalised, and her symptoms resolved. Few studies have examined the incidence and mechanism by which hydralazine induces a liver injury pattern. With this case, we review the literature, the pathogenesis involved and the eventual management of hydralazine-induced liver injury. We propose close monitoring of liver enzymes for patients on hydralazine throughout their treatment course.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Doença Hepática Induzida por Substâncias e Drogas , Hipertensão , Anti-Hipertensivos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Crônica Induzida por Substâncias e Drogas/tratamento farmacológico , Feminino , Humanos , Hidralazina/efeitos adversos , Hipertensão/tratamento farmacológico , Pessoa de Meia-Idade
16.
Drugs Aging ; 38(10): 921-930, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34405381

RESUMO

BACKGROUND: There is ongoing debate about the associations between drug therapies targeting the renin-angiotensin-aldosterone system (RAAS) and adverse outcomes in coronavirus disease 2019 (COVID-19). OBJECTIVE: This study aims to examine the associations between using medications for the cardiovascular system and the risks associated with COVID-19 in middle-aged and older adults. METHODS: A total of 77,221 participants (aged 50-86 years) from UK Biobank were tested for SARS-CoV-2 RNA. The medications included angiotensin-converting enzyme inhibitors (ACEI), angiotensin-receptor blockers (ARB), ß-blockers, calcium channel blockers (CCB), statins, and aspirin. COVID-19 outcomes comprised a positive test result and severity of COVID-19 (defined as mild, hospitalization or death). We evaluated the risk among total participants and for sub-groups based on sex. Propensity score matching was performed 1:1 and logistic regression models were used. RESULTS: Among the middle- and older aged participants, no significant associations between any class of medications and the likelihood of COVID-19 infection were observed. ACEI were associated with a higher mortality risk from COVID-19 (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.01-1.32) and CCB were associated with a lower hospitalization risk for COVID-19 (OR 0.87, 95% CI 0.79-0.96) among the male patients with COVID-19, while a lower mortality risk from COVID-19 (OR 0.67, 95% CI 0.47-0.96) was observed with ARB among the female patients with COVID-19. CONCLUSIONS: The study suggested sex differences in the risk of death from COVID-19 with the use of ACEI and ARB among middle-aged and older adults. Sex differences in the risk of hospitalization for COVID-19 with the use of CCB was observed as well. It is of clinical importance that clinicians adopt different CVD treatment approaches for female and male patients with COVID-19.


Assuntos
COVID-19 , Hipertensão , Idoso , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Feminino , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , RNA Viral , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Caracteres Sexuais
17.
Medicine (Baltimore) ; 100(29): e26724, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34398046

RESUMO

ABSTRACT: To evaluate the duration of topical brimonidine therapy before the onset of brimonidine-related allergic conjunctivitis and the clinical characteristics associated with the development of brimonidine allergy.We retrospectively enrolled patients who presented brimonidine allergy from December 1, 2008 to November 30, 2020. The duration of brimonidine treatment, concomitant medications, benzalkonium chloride (BAK) exposure, change in IOP, and season of onset were evaluated.292 patients were included, among which 147 were female and 145 were male. The mean age was 58.3 ± 13.6 years old. The mean (median) duration of brimonidine therapy was 266.6 (196) days, with a peak at 60-120 days. The duration was similar whether the patients received brimonidine monotreatment or in combination with other glaucoma drugs, with or without BAK. The IOP increased by 5.6% after brimonidine allergy (P < .001), which was even higher in the brimonidine monotherapy group (9.2%, P < .001). There was no significant IOP elevation in patients treated with multiple glaucoma medications.Around half of brimonidine allergy occurred within 6 months, with a peak in 2 to 4 months. The duration did not differ in patients receiving brimonidine monotherapy or multiple glaucoma medications. The presence of BAK did not affect the duration either. When brimonidine allergy occurred, there was a loss of IOP control, especially in patients receiving brimonidine monotherapy. It is recommended to switch to other types of glaucoma medications for better IOP control.


Assuntos
Anti-Hipertensivos/efeitos adversos , Tartarato de Brimonidina/efeitos adversos , Conjuntivite Alérgica/epidemiologia , Soluções Oftálmicas/efeitos adversos , Anti-Hipertensivos/administração & dosagem , Tartarato de Brimonidina/administração & dosagem , Conjuntivite Alérgica/induzido quimicamente , Esquema de Medicação , Feminino , Seguimentos , Glaucoma/tratamento farmacológico , Humanos , Pressão Intraocular , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas/administração & dosagem , Estudos Retrospectivos
18.
Medicine (Baltimore) ; 100(34): e26874, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34449456

RESUMO

ABSTRACT: The distribution of prostaglandin-associated periorbitopathy (PAP) graded using the Shimane University PAP Grading System (SU-PAP) among glaucoma/ocular hypertension subjects using a topical FP or EP2 receptor agonist was reported. A 460 consecutive 460 Japanese subjects (211 men, 249 women; mean age ±â€Šstandard deviation, 69.9 ±â€Š14.5 years) who had used either a FP agonist (0.005% latanoprost, 0.0015% tafluprost, 0.004% travoprost, 0.03% bimatoprost, or fixed combinations of these) or EP2-agonist (0.002% omidenepag isopropyl) for more than 3 months in at least 1 eye were retrospectively enrolled. Age, sex, prostaglandin, intraocular pressure (IOP) measured by Goldmann applanation tonometry (IOPGAT) and iCare rebound tonometry (IOPRBT), difference between IOPGAT and IOPRBT (IOPGAT-RBT), PAP grade, and PAP grading items were compared among groups stratified by PAP grade or prostaglandins. Of the study patients, 114 (25%) had grade 0 (no PAP), 174 (38%) grade 1 (superficial cosmetic PAP), 141 (31%) grade 2 (deep cosmetic PAP), and 31 (7%) grade 3 (tonometric PAP). The IOPGAT was significantly higher in grade 3 (17.5 ±â€Š5.4 mm Hg) than grades 0 (15.0 ±â€Š5.1 mm Hg, P = .032) and 1 (14.5 ±â€Š4.2 mm Hg, P = .008), and the IOPGAT-RBT was significantly higher in grade 3 (5.8 ±â€Š3.2 mm Hg) than the other 3 grades (1.3-1.9 mm Hg, P < .001 for all comparisons); the IOPRBT was equivalent among the 4 grades. The PAP grade was significantly higher associated with travoprost (2.0 ±â€Š0.8) and bimatoprost (2.0 ±â€Š0.7) than latanoprost (1.0 ±â€Š0.8, P < .001 for both comparisons) and tafluprost (1.0 ±â€Š0.7, P < .001 for both comparisons), but significantly lower associated with omidenepag (0.0 ±â€Š0.0, P < .001 for all comparisons) than the other 4 prostaglandins. Multivariate analyses showed older age (standard ß = 0.11), travoprost (0.53, referenced by latanoprost) and bimatoprost (0.65) were associated with higher PAP grades, while tafluprost (-0.18) and omidenepag (-0.73) were associated with lower PAP grades. The PAP graded using SU-PAP reflects the degree of overestimation of the IOPGAT and different severities of PAP among the different prostaglandins. SU-PAP, the grade system constructed based on the underlining mechanisms of PAP, is a simple grading system for PAP that is feasible for use in a real-world clinical situation.


Assuntos
Anti-Hipertensivos/efeitos adversos , Glaucoma/tratamento farmacológico , Hipertensão Ocular/tratamento farmacológico , Doenças Orbitárias/induzido quimicamente , Prostaglandinas Sintéticas/efeitos adversos , Fatores Sexuais , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Bimatoprost/efeitos adversos , Cloprostenol/efeitos adversos , Combinação de Medicamentos , Feminino , Humanos , Pressão Intraocular , Latanoprosta/efeitos adversos , Masculino , Manometria , Pessoa de Meia-Idade , Prostaglandinas F/efeitos adversos , Estudos Retrospectivos , Índice de Gravidade de Doença , Travoprost/efeitos adversos
19.
Pol Merkur Lekarski ; 49(292): 303-305, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34464373

RESUMO

Clinical consequences of hyponatremia might be serious. It is often related to the administration of diuretics, especially thiazide and thiazide-like diuretics. It is known that elderly subjects are prone to thiazide induced hyponatremia (TIH). A CASE REPORT: A 66-year old female patient was admitted to our Department. The aim of the admission was to complete a differential diagnosis of chronic hyponatremia. For about two years the patient had suffered from the following symptoms: severe headaches, fatigue, episodic mental confusions, stomachaches, and diarrhea. Before admission to the hospital, the patient was treated with bisoprolol, amlodipine, telmisartan, indapamide, furosemide, acetylsalicylic acid, thiamazole, and zolpidem. The general clinical picture might suggest that the cause of hyponatremia was the indapamide diuretic therapy. However, only moderate hyponatremia, normokalemia, as well as, an increased antidiuretic hormone serum concentration were observed. These findings are not typical for TIH. Despite those findings, natremia improved after the cessation of indapamide therapy. CONCLUSIONS: This case report described the atypical presentation of TIH resembling SIADH. TIH diagnosis should be primarily based on the improvement of hyponatremia after the termination of thiazide or thiazide-like diuretic treatment.


Assuntos
Anti-Hipertensivos , Hiponatremia , Idoso , Anti-Hipertensivos/efeitos adversos , Diuréticos/efeitos adversos , Feminino , Humanos , Hiponatremia/induzido quimicamente , Hiponatremia/diagnóstico , Tiazidas
20.
Clin Sci (Lond) ; 135(13): 1609-1625, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34240734

RESUMO

Cardiovascular disease remains the primary cause of mortality globally, being responsible for an estimated 17 million deaths every year. Cancer is the second leading cause of death on a global level with roughly 9 million deaths per year being attributed to neoplasms. The two share multiple common risk factors such as obesity, poor physical exercise, older age, smoking and there exists rare monogenic hypertension syndromes. Hypertension is the most important risk factor for cardiovascular disease and affects more than a billion people worldwide and may also be a risk factor for the development of certain types of cancer (e.g. renal cell carcinoma (RCC)). The interaction space of the two conditions becomes more complicated when the well-described hypertensive effect of certain antineoplastic drugs is considered along with the extensive amount of literature on the association of different classes of antihypertensive drugs with cancer risk/prevention. The cardiovascular risks associated with antineoplastic treatment calls for efficient management of relative adverse events and the development of practical strategies for efficient decision-making in the clinic. Pharmacogenetic interactions between cancer treatment and hypertension-related genes is not to be ruled out, but the evidence is not still ample to be incorporated in clinical practice. Precision Medicine has the potential to bridge the gap of knowledge regarding the full spectrum of interactions between cancer and hypertension (and cardiovascular disease) and provide novel solutions through the emerging field of cardio-oncology. In this review, we aimed to examine the bidirectional associations between cancer and hypertension including pharmacotherapy.


Assuntos
Anti-Hipertensivos/uso terapêutico , Antineoplásicos/uso terapêutico , Hipertensão/tratamento farmacológico , Neoplasias/tratamento farmacológico , Animais , Anti-Hipertensivos/efeitos adversos , Antineoplásicos/efeitos adversos , Humanos , Hipertensão/epidemiologia , Hipertensão/genética , Neoplasias/epidemiologia , Neoplasias/genética , Prognóstico , Fatores de Proteção , Medição de Risco , Fatores de Risco
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