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1.
Hypertension ; 75(1): 23-32, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31786973

RESUMO

Current cardiovascular pharmacotherapy targets maladaptive overactivation of the renin-angiotensin-aldosterone system (RAAS), which occurs throughout the continuum of cardiovascular disease spanning from hypertension to heart failure with reduced ejection fraction. Over the past 16 years, 4 prospective, randomized, placebo-controlled clinical trials using candesartan, perindopril, irbesartan, and spironolactone in patients with heart failure with preserved ejection fraction (HFpEF) failed to demonstrate increased efficacy of RAAS blockade added to guideline-directed medical therapy. We reappraise these trials and their weaknesses, which precluded statistically significant findings. Recently, dual-acting RAAS blockade with sacubitril-valsartan relative to stand-alone valsartan failed to improve outcome in the PARAGON-HF trial (Efficacy and Safety of LCZ696 Compared with Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction). The majority of patients with HFpEF experience hypertension, frequently with subclinical left ventricular dysfunction, contributed to by comorbidities such as coronary disease, diabetes mellitus, overweight, and atrial fibrillation. Contrasting the findings in HFpEF, trials evaluating RAAS blockade on either side of HFpEF on the cardiovascular continuum in patients with high-risk hypertension and heart failure with reduced ejection fraction, respectively, showed positive outcomes. We do not have a biologically plausible explanation for such divergent efficacy of RAAS blockade. Based on considerations of well-established clinical efficacy in hypertension and heart failure with reduced ejection fraction and the shortcomings of aforementioned clinical trials in HFpEF, we argue that RAAS blockers including MRAs (mineralocorticoid receptor antagonists; aldosterone antagonists) should be used in the treatment of patients with HFpEF.

2.
J Am Coll Cardiol ; 74(23): 2893-2904, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31806133

RESUMO

BACKGROUND: Moderate and moderately severe renal impairment are common in patients with heart failure and reduced ejection fraction, but whether beta-blockers are effective is unclear, leading to underuse of life-saving therapy. OBJECTIVES: This study sought to investigate patient prognosis and the efficacy of beta-blockers according to renal function using estimated glomerular filtration rate (eGFR). METHODS: Analysis of 16,740 individual patients with left ventricular ejection fraction <50% from 10 double-blind, placebo-controlled trials was performed. The authors report all-cause mortality on an intention-to-treat basis, adjusted for baseline covariates and stratified by heart rhythm. RESULTS: Median eGFR at baseline was 63 (interquartile range: 50 to 77) ml/min/1.73 m2; 4,584 patients (27.4%) had eGFR 45 to 59 ml/min/1.73 m2, and 2,286 (13.7%) 30 to 44 ml/min/1.73 m2. Over a median follow-up of 1.3 years, eGFR was independently associated with mortality, with a 12% higher risk of death for every 10 ml/min/1.73 m2 lower eGFR (95% confidence interval [CI]: 10% to 15%; p < 0.001). In 13,861 patients in sinus rhythm, beta-blockers reduced mortality versus placebo; adjusted hazard ratio (HR): 0.73 for eGFR 45 to 59 ml/min/1.73 m2 (95% CI: 0.62 to 0.86; p < 0.001) and 0.71 for eGFR 30 to 44 ml/min/1.73 m2 (95% CI: 0.58 to 0.87; p = 0.001). The authors observed no deterioration in renal function over time in patients with moderate or moderately severe renal impairment, no difference in adverse events comparing beta-blockers with placebo, and higher mortality in patients with worsening renal function on follow-up. Due to exclusion criteria, there were insufficient patients with severe renal dysfunction (eGFR <30 ml/min/1.73 m2) to draw conclusions. In 2,879 patients with atrial fibrillation, there was no reduction in mortality with beta-blockers at any level of eGFR. CONCLUSIONS: Patients with heart failure, left ventricular ejection fraction <50% and sinus rhythm should receive beta-blocker therapy even with moderate or moderately severe renal dysfunction.

3.
Am Heart J ; 215: 83-90, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31291604

RESUMO

BACKGROUND: Reduced left ventricular ejection fraction (LVEF) after acute myocardial infarction (MI) increases risk of cardiovascular (CV) hospitalizations, but evidence regarding its association with non-CV outcome is scarce. We investigated the association between LVEF and adjudicated cause-specific hospitalizations following MI complicated with low LVEF or overt heart failure (HF). METHODS: In an individual patient data meta-analysis of 19,740 patients from 3 large randomized trials, Fine and Gray competing risk modeling was performed to study the association between LVEF and hospitalization types. RESULTS: The most common cause of hospitalization was non-CV (n = 2,368 for HF, n = 1,554 for MI, and n = 3,703 for non-CV). All types of hospitalizations significantly increased with decreasing LVEF. The absolute risk increase associated with LVEF ≪25% (vs LVEF ≫35%) was 15.5% (95% CI 13.4-17.5) for HF, 4.7% (95% CI 3.0-6.4) for MI, and 10.4% (95% CI 8.0-12.8) for non-CV hospitalization. On a relative scale, after adjusting for confounders, each 5-point decrease in LVEF was associated with an increased risk of HF (hazard ratio [HR] 1.15, 95% CI 1.12-1.18), MI (HR 1.06, 95% CI 1.03-1.10), and non-CV hospitalization (HR 1.03, 95% CI 1.01-1.05). CONCLUSIONS: In a high-risk population with complicated acute MI, the absolute risk increase in non-CV hospitalizations associated with LVEF ≪25% was two thirds of the absolute risk increase in HF hospitalizations and twice the absolute risk increase in MI hospitalizations. LVEF was an independent predictor of all types of hospitalization and appears as an integrative marker of sicker patient status.

4.
Am J Ther ; 26(6): e671-e678, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31145139

RESUMO

BACKGROUND: Many patients with heart failure (HF) are treated with warfarin or non-vitamin K oral anticoagulants (NOACs). Randomized outcome-driven comparisons of different anticoagulant strategies in HF are lacking. Data from international, government-mandated registries may be useful in understanding the real-life use of various anticoagulants and how they are linked to outcomes. STUDY QUESTION: To assess 2015 annual all-cause mortality, myocardial infarction, and stroke rates co-reported for warfarin and NOACs in subjects with and without HF in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. STUDY DESIGN: We extracted and examined outcome cases in subjects with HF and on warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban and stratified these according to anticoagulants. MEASURES AND OUTCOMES: Annual all-cause mortality, myocardial infarction, and stroke in FAERS. ANALYSIS METHOD: Odds ratio (OR) and χ(Equation is included in full-text article.)for oral anticoagulants from FAERS with and without HF among complete primary reports issued in 2015. RESULTS: FAERS reported 137,026 HF cases, with death co-reported in 42,942 (31.3%). In total, 11,278 (8.2%) HF patients were treated with anticoagulants, with more prescribed warfarin (n = 8260) than all NOACs combined (n = 3018). Very few reports for edoxaban were available. Warfarin consistently displayed a signal for excess adverse events compared to NOACs: OR (95% confidence interval) for the composite of mortality, myocardial infarction, and stroke were 1.91 (1.76-2.07) versus apixaban, 1.92 (1.81-2.03) versus dabigatran, 4.09 (3.38-4.37) versus rivaroxaban, and 2.64 (2.53-2.76) versus all NOACs combined (all P < 0.001). Warfarin, compared to all NOACs combined, demonstrated higher rates of all-cause mortality [OR = 2.69 (95% confidence interval, 2.49-2.90)], myocardial infarction [5.30 (4.17-6.74)], stroke [OR = 8.85 (6.61-11.84)], and ischemic stroke [OR = 12.73 (8.87-18.27); all P < 0.001]. CONCLUSIONS: Annual 2015 FAERS profiles in HF patients reveal that warfarin was numerically dominant. Warfarin was associated with higher risk of death, myocardial infarction, and stroke compared to NOACs. These observational data provide real-world insight into a potential safety benefit of NOACs over warfarin in the setting of HF.

6.
Cardiovasc Res ; 115(2): 266-276, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30475996

RESUMO

There is growing evidence from Phase III randomized clinical trials of the cardiovascular benefits of sodium glucose cotransporter 2 (SGLT2) inhibitors in patients with diabetes mellitus. It is hypothesized that these benefits are mediated by mechanisms other than glucose control. To address this, we performed a systematic review of data from preclinical studies examining the direct cardioprotective effects of SGLT2 inhibitors. Medline, EMBASE, CINAHL, and International Pharmaceutical Abstracts databases were searched for preclinical studies that examined the potential cardioprotective effects of SGLT2 inhibitors. Submission documents to the US Food and Drug Administration, European Medicines Agency, and Japanese Pharmaceutical and Medical Devices Agency for the registration of SGLT2 inhibitors were also reviewed. A total of 36 reports were included in the final analysis. The potential direct cardiovascular benefits of SGLT2 inhibitors include: augmentation of signal transducer and activator of transcription 3; inhibition of sodium hydrogen exchange; reduction of atherosclerosis; modulation of natriuretic peptides; vasodilation; modulation of sympathetic tone; and reduction of inflammation, oxidative stress, endoplasmic reticulum stress, and cardiac glucose uptake via down-regulation of SGLT1 expression. There are a number of mechanisms by which SGLT2 inhibitors may exert cardiovascular benefits beyond glycaemic control.

7.
Int J Cardiol ; 272: 260-266, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30144995

RESUMO

BACKGROUND: Identifying risk factors for specific modes of death in patients with heart failure (HF) or left ventricular (LV) dysfunction after acute myocardial infarction (MI) may help to avert events. We sought to evaluate LV ejection fraction (LVEF) as a prognosticator of specific death modes. METHODS AND RESULTS: In an individual patient data meta-analysis of four merged trials (CAPRICORN, EPHESUS, OPTIMAAL, and VALIANT), Cox modelling was performed to study the association between baseline LVEF from 19,740 patients and types of death during follow-up. Over a median follow-up of 707 days 3419 deaths occurred. The distribution pattern for mode of death was similar across categories (LVEF < 25%, LVEF 25-35%, and LVEF > 35%). In multivariable models, the risk of all types of death increased with decreasing LVEF. If compared to LVEF > 35%, LVEF < 25% was associated with a 113% increased risk of sudden death (hazard ratio (HR) 2.13, 95% confidence interval (CI) 1.53-2.98), a 170% increased risk of HF death (HR 2.70, 95% CI 1.83-3.98), a 66% increased risk of other cardiovascular (CV) death (HR 1.66, 95% CI 1.14-2.42), and a 90% increased risk of non CV death (HR 1.90, 95% CI 1.15-3.14). CONCLUSION: In patients with HF or LV dysfunction after acute MI, low LVEF is a ubiquitous risk marker associated with death regardless of type. The different modes of death are fairly equally represented throughout the categories of LVEF and sudden death remains a significant mode of death also in patients with LVEF > 35%.


Assuntos
Causas de Morte/tendências , Insuficiência Cardíaca/mortalidade , Infarto do Miocárdio/mortalidade , Disfunção Ventricular Esquerda/mortalidade , Função Ventricular Esquerda/fisiologia , Idoso , Método Duplo-Cego , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/fisiopatologia , Fatores de Risco , Volume Sistólico , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia
9.
Int J Cardiol ; 258: 192-198, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29544929

RESUMO

BACKGROUND: Angiotensin receptor neprilysin inhibitor (ARNi) enhances beneficial natriuretic peptides by inhibiting their breakdown through neprilysin. Although the first-in-class ARNi sacubitril/valsartan (LCZ696) reduced mortality and morbidity in heart failure (HF) with reduced ejection fraction (EF) compared to angiotensin converting enzyme inhibitor (ACEi), mechanistic data on ARNi are scarce. ARNi may be superior to ACEi in attenuating adverse cardiac remodeling and dysfunction post-myocardial infarction (MI). METHODS: Rats randomized at 1 week post-MI were administered LCZ696 (60 mg/kg, N = 12), the ACEi perindopril (2 mg/kg, N = 11) or vehicle (corn oil, N = 13), orally for 4 weeks. Sham rats received vehicle (corn oil, N = 9). Echocardiography was assessed before and after treatment, prior to invasive hemodynamics using pressure-volume analysis. Hypertrophy and fibrosis was evaluated by histochemical staining, and analysis of myocardial gene and protein expression using real-time quantitative PCR and Western blot. RESULTS: Compared to Sham, MI groups had large infarcts (>40%) and reduced left ventricular (LV) EF. LCZ696 improved LVEF and end systolic pressure-volume relationship compared to perindopril (P < 0.05). LCZ696 but not perindopril reduced lung weight and LV filling pressures post-MI. Reductions in cardiac hypertrophy and fibrosis were similar, however gene expression of hypertrophic markers, ANP and ßMHC were reduced with LCZ696 versus perindopril. LCZ696 versus perindopril reduced myocardial TIMP2 gene expression with a trend (P = 0.067) to lowering collagen I. CONCLUSION: LCZ696 attenuated adverse cardiac remodeling and dysfunction and reduced pulmonary congestion and hypertrophic markers after MI compared to perindopril. This study supports clinical evaluation of ARNi versus ACEi in targeting post-MI cardiac dysfunction and remodeling.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Cardiotônicos/uso terapêutico , Modelos Animais de Doenças , Infarto do Miocárdio/prevenção & controle , Neprilisina/antagonistas & inibidores , Aminobutiratos/uso terapêutico , Animais , Masculino , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/fisiopatologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Tetrazóis/uso terapêutico
10.
Eur Heart J ; 39(1): 26-35, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29040525

RESUMO

Aims: Recent guidelines recommend that patients with heart failure and left ventricular ejection fraction (LVEF) 40-49% should be managed similar to LVEF ≥ 50%. We investigated the effect of beta-blockers according to LVEF in double-blind, randomized, placebo-controlled trials. Methods and results: Individual patient data meta-analysis of 11 trials, stratified by baseline LVEF and heart rhythm (Clinicaltrials.gov: NCT0083244; PROSPERO: CRD42014010012). Primary outcomes were all-cause mortality and cardiovascular death over 1.3 years median follow-up, with an intention-to-treat analysis. For 14 262 patients in sinus rhythm, median LVEF was 27% (interquartile range 21-33%), including 575 patients with LVEF 40-49% and 244 ≥ 50%. Beta-blockers reduced all-cause and cardiovascular mortality compared to placebo in sinus rhythm, an effect that was consistent across LVEF strata, except for those in the small subgroup with LVEF ≥ 50%. For LVEF 40-49%, death occurred in 21/292 [7.2%] randomized to beta-blockers compared to 35/283 [12.4%] with placebo; adjusted hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.34-1.03]. Cardiovascular death occurred in 13/292 [4.5%] with beta-blockers and 26/283 [9.2%] with placebo; adjusted HR 0.48 (95% CI 0.24-0.97). Over a median of 1.0 years following randomization (n = 4601), LVEF increased with beta-blockers in all groups in sinus rhythm except LVEF ≥50%. For patients in atrial fibrillation at baseline (n = 3050), beta-blockers increased LVEF when < 50% at baseline, but did not improve prognosis. Conclusion: Beta-blockers improve LVEF and prognosis for patients with heart failure in sinus rhythm with a reduced LVEF. The data are most robust for LVEF < 40%, but similar benefit was observed in the subgroup of patients with LVEF 40-49%.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Insuficiência Cardíaca , Volume Sistólico/fisiologia , Idoso , Fibrilação Atrial , Método Duplo-Cego , Feminino , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Int J Cardiol ; 249: 274-281, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-28964557

RESUMO

BACKGROUND: Heart rate has been reported to be associated with adverse outcome in heart failure (HF) and myocardial infarction (MI), but conflicting evidence exists regarding its impact in patients with associated atrial fibrillation (AF). OBJECTIVES: We investigated the differential impact of heart rate on clinical outcomes according to the presence or absence of AF in patients with reduced systolic function and/or HF after MI. METHODS: We studied the association of heart rate with outcome using Cox-models in a merged dataset (n=28,771) of four randomized trials (CAPRICORN, EPHESUS, OPTIMAAL, and VALIANT). RESULTS: At baseline, 3736 (13%) patients had AF. We identified a significant interaction between AF and heart rate, and a decreasing effect of heart rate with time, heart rate being less associated with outcome after 1year of follow-up (both p for interaction <0.001). We report associations with outcome separately in patients with and without AF. In addition, as neutral associations with outcome after 1year were estimated after adjustment on confounding factors, only association for the first year follow-up were provided. 10-bpm increase in heart rate conferred increased risk for all-cause mortality (1.27 [1.21 to 1.33], p<0.0001), CV-mortality (1.28 [1.22 to 1.34], p<0.0001), and HF-hospitalisation (1.25 [1.19 to 1.31], p<0.0001) in patients without AF. In contrast, in patients with AF, the incremental risk for 10-bpm increase in heart rate was attenuated for all-cause (1.14 [1.06 to 1.23], p=0.0007), CV-mortality (1.12 [1.03 to 1.22], p=0.006), and HF-hospitalisation (1.16 [1.07 to 1.26], p=0.0006, p for interaction with AF <0.001 for all outcomes). CONCLUSIONS: In patients with reduced systolic function and/or HF post-MI, higher heart rate predicts increased major cardiovascular events during the first year following MI in patients without AF. This association is markedly attenuated in subjects with AF.


Assuntos
Bases de Dados Factuais/tendências , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca/fisiologia , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Valor Preditivo dos Testes , Fatores de Risco , Taxa de Sobrevida/tendências , Resultado do Tratamento
12.
Card Fail Rev ; 3(1): 19-24, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28785471

RESUMO

A key feature of chronic heart failure (HF) is the sustained activation of endogenous neurohormonal systems in response to impaired cardiac pumping and/or filling properties. The clinical use of neurohormonal blockers has revolutionised the care of HF patients over the past three decades. Drug therapy that is active against imbalance in both the autonomic and renin-angiotensin-aldosterone systems consistently reduces morbidity and mortality in chronic HF with reduced left ventricular ejection fraction and in sinus rhythm. This article provides an assessment of the major neurohormonal systems and their therapeutic blockade in patients with chronic HF.

13.
J Am Coll Cardiol ; 69(24): 2885-2896, 2017 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-28467883

RESUMO

BACKGROUND: The relationship between mortality and heart rate remains unclear for patients with heart failure with reduced ejection fraction in either sinus rhythm or atrial fibrillation (AF). OBJECTIVES: This analysis explored the prognostic importance of heart rate in patients with heart failure with reduced ejection fraction in randomized controlled trials comparing beta-blockers and placebo. METHODS: The Beta-Blockers in Heart Failure Collaborative Group performed a meta-analysis of harmonized individual patient data from 11 double-blind randomized controlled trials. The primary outcome was all-cause mortality, analyzed with Cox proportional hazard ratios (HR) modeling heart rate measured at baseline and approximately 6 months post-randomization. RESULTS: A higher heart rate at baseline was associated with greater all-cause mortality for patients in sinus rhythm (n = 14,166; adjusted HR: 1.11 per 10 beats/min; 95% confidence interval [CI]: 1.07 to 1.15; p < 0.0001) but not in AF (n = 3,034; HR: 1.03 per 10 beats/min; 95% CI: 0.97 to 1.08; p = 0.38). Beta-blockers reduced ventricular rate by 12 beats/min in both sinus rhythm and AF. Mortality was lower for patients in sinus rhythm randomized to beta-blockers (HR: 0.73 vs. placebo; 95% CI: 0.67 to 0.79; p < 0.001), regardless of baseline heart rate (interaction p = 0.35). Beta-blockers had no effect on mortality in patients with AF (HR: 0.96, 95% CI: 0.81 to 1.12; p = 0.58) at any heart rate (interaction p = 0.48). A lower achieved resting heart rate, irrespective of treatment, was associated with better prognosis only for patients in sinus rhythm (HR: 1.16 per 10 beats/min increase, 95% CI: 1.11 to 1.22; p < 0.0001). CONCLUSIONS: Regardless of pre-treatment heart rate, beta-blockers reduce mortality in patients with heart failure with reduced ejection fraction in sinus rhythm. Achieving a lower heart rate is associated with better prognosis, but only for those in sinus rhythm.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Frequência Cardíaca/fisiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Prognóstico , Volume Sistólico/fisiologia
14.
BMJ ; 353: i1855, 2016 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-27098105

RESUMO

OBJECTIVES: To determine the efficacy and tolerability of ß blockers in a broad age range of women and men with heart failure with reduced ejection fraction (HFrEF) by pooling individual patient data from placebo controlled randomised trials. DESIGN: Prospectively designed meta-analysis of individual patient data from patients aged 40-85 in sinus rhythm at baseline, with left ventricular ejection fraction <0.45. PARTICIPANTS: 13,833 patients from 11 trials; median age 64; 24% women. MAIN OUTCOME MEASURES: The primary outcome was all cause mortality; the major secondary outcome was admission to hospital for heart failure. Analysis was by intention to treat with an adjusted one stage Cox proportional hazards model. RESULTS: Compared with placebo, ß blockers were effective in reducing mortality across all ages: hazard ratios were 0.66 (95% confidence interval 0.53 to 0.83) for the first quarter of age distribution (median age 50); 0.71 (0.58 to 0.87) for the second quarter (median age 60); 0.65 (0.53 to 0.78) for the third quarter (median age 68); and 0.77 (0.64 to 0.92) for the fourth quarter (median age 75). There was no significant interaction when age was modelled continuously (P=0.1), and the absolute reduction in mortality was 4.3% over a median follow-up of 1.3 years (number needed to treat 23). Admission to hospital for heart failure was significantly reduced by ß blockers, although this effect was attenuated at older ages (interaction P=0.05). There was no evidence of an interaction between treatment effect and sex in any age group. Drug discontinuation was similar regardless of treatment allocation, age, or sex (14.4% in those give ß blockers, 15.6% in those receiving placebo). CONCLUSION: Irrespective of age or sex, patients with HFrEF in sinus rhythm should receive ß blockers to reduce the risk of death and admission to hospital.Registration PROSPERO CRD42014010012; Clinicaltrials.gov NCT00832442.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Volume Sistólico/fisiologia , Resultado do Tratamento
17.
Curr Heart Fail Rep ; 13(1): 1-12, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26829930

RESUMO

Compared to men, women with heart failure (HF) are often older, smoke less, and have more preserved ejection fraction (EF) and hypertensive HF rather than HF of ischemic etiology. Gender-stratified outcomes on comorbidities data in HF are scarce. Women have traditionally been underrepresented in HF trials. Although data suggest that overall prognosis may be better in women, they experience lower quality of life with greater functional impairment from HF compared to men. Gender differences have been reported for comorbid diabetes, chronic obstructive pulmonary disease, renal dysfunction, anemia, and depression and may explain gender disparity in outcomes. However, possible confounding of comorbidities with known prognostic determinants in HF (such as EF) as well as gender differences in the utilization of medical therapies obscures interpretation. In this review, we will explore the evidence for gender differences in non-cardiovascular comorbidities in HF. Our findings may guide clinicians to individualize HF care, according to best practice, in the hope of improving prognosis for this chronic and debilitating condition.


Assuntos
Insuficiência Cardíaca/epidemiologia , Anemia/epidemiologia , Artrite/epidemiologia , Comorbidade , Depressão/epidemiologia , Diabetes Mellitus/epidemiologia , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Fatores Sexuais
18.
Eur J Heart Fail ; 17(11): 1144-51, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26424212

RESUMO

AIMS: Serum uric acid (SUA) levels are associated with poorer outcomes in healthy cohorts and patients with stable and unstable coronary heart disease. We investigated the relationship between SUA and clinical outcomes in subjects with acute myocardial infarction (MI) complicated by reduced left ventricular (LV) function, heart failure (HF), or both. METHODS AND RESULTS: Univariable and multivariable Cox proportional hazards modelling was performed to study the association of baseline SUA and all-cause mortality, cardiovascular (CV) mortality, and HF hospitalization in an individual patient meta-analysis of four merged large randomized trials (CAPRICORN, EPHESUS, OPTIMAAL, and VALIANT). Three trials (excluding VALIANT) reported SUA, which was available in a total of 12 677 subjects. The ranges of SUA for quartiles I-IV were 45-280, 281-344, 345-420, and 420-1640 mmol/L, respectively. While almost 90% of patients in the lowest SUA quartile were alive after a mean follow-up of 23 ± 11 months, <70% were alive in the highest SUA quartile. Compared with the lowest SUA quartile as reference, hazard ratios (HRs) and 95% confidence intervals (CIs) of SUA quartiles III and IV showed an increase in all-cause mortality [HR 1.18, 95% CI 0.95-1.46, and HR 1.36, 95% CI 1.11-1.67) and CV mortality (HR 1.27, 95% 1.01-1.61, and HR 1.47, 95% CI 1.17-1.83). SUA quartiles III and IV also exhibited increased HF hospitalization (HR 1.22, 95% CI 1.09-1.36, and HR 1.28, 95% CI 1.14-1.43; P < 0.001 for all comparisons) in multivariable analyses. The addition of SUA was associated with a significant improvement in reclassification to predict CV mortality (net reclassification improvement 17.6%, 95% CI 14.9-20.5%, P < 0.001). CONCLUSIONS: Elevated SUA is associated with poor outcomes in patients after MI complicated by reduced LV function, HF, or both. The quantification of SUA, a low-cost routinely available biomarker, could improve risk stratification of patients with complicated MI.


Assuntos
Insuficiência Cardíaca , Infarto do Miocárdio , Ácido Úrico/sangue , Disfunção Ventricular Esquerda , Idoso , Biomarcadores/sangue , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/mortalidade , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Estatística como Assunto , Disfunção Ventricular Esquerda/sangue , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia
19.
Nat Rev Cardiol ; 12(12): 730-40, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26416006

RESUMO

Heart failure (HF) can rightfully be called the epidemic of the 21(st) century. Historically, the only available medical treatment options for HF have been diuretics and digoxin, but the capacity of these agents to alter outcomes has been brought into question by the scrutiny of modern clinical trials. In the past 4 decades, neurohormonal blockers have been introduced into clinical practice, leading to marked reductions in morbidity and mortality in chronic HF with reduced left ventricular ejection fraction (LVEF). Despite these major advances in pharmacotherapy, our understanding of the underlying disease mechanisms of HF from epidemiological, clinical, pathophysiological, molecular, and genetic standpoints remains incomplete. This knowledge gap is particularly evident with respect to acute decompensated HF and HF with normal (preserved) LVEF. For these clinical phenotypes, no drug has been shown to reduce long-term clinical event rates substantially. Ongoing developments in the pharmacotherapy of HF are likely to challenge our current best-practice algorithms. Novel agents for HF therapy include dual-acting neurohormonal modulators, contractility-enhancing agents, vasoactive and anti-inflammatory peptides, and myocardial protectants. These novel compounds have the potential to enhance our armamentarium of HF therapeutics.


Assuntos
Insuficiência Cardíaca/terapia , Amidas/administração & dosagem , Aminobutiratos/administração & dosagem , Fator Natriurético Atrial/administração & dosagem , Digoxina/administração & dosagem , Fumaratos/administração & dosagem , Humanos , Peptídeos Natriuréticos/administração & dosagem , Fragmentos de Peptídeos/administração & dosagem , Venenos de Serpentes/administração & dosagem , Tetrazóis/administração & dosagem
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