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2.
Clin Res Cardiol ; 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32253507

RESUMO

BACKGROUND: Plasma volume (PV) estimated from Duarte's formula (based on hemoglobin/hematocrit) has been associated with poor prognosis in patients with heart failure (HF). There are, however, limited data regarding the association of estimated PV status (ePVS) derived from hemoglobin/hematocrit with clinical profiles and study outcomes in patients with HF and preserved ejection fraction (HFpEF). METHODS AND RESULTS: Patients from North and South America enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial (TOPCAT) with available hemoglobin/hematocrit data were studied. The association between ePVS (Duarte formula and Hakim formula) and the composite of cardiovascular mortality, HF hospitalization, or aborted cardiac arrest was assessed. Among 1747 patients (age 71.6 years; males 50.1%), mean ePVS derived from Duarte formula was 4.9 ± 1.0 mL/g. Higher Duarte-derived ePVS was associated with prior HF admission, diabetes, more severe congestion, poor renal function, higher natriuretic peptide level, and E/e'. After adjustment for potential covariates including natriuretic peptide, higher Duarte-derived ePVS was associated with an increased rate of the primary outcome [highest vs. lowest ePVS quartile: adjusted-HR (95%CI) = 1.79 (1.28-2.50), p < 0.001]. Duarte-derived ePVS improved prognostic performance on top of clinical and routine variables (including natriuretic peptides) (NRI = 11, p < 0.001), whereas Hakim-derived ePVS did not (p = 0.59). The prognostic value of Duarte-derived ePVS was not modified by renal function (P interaction > 0.10 for all outcomes). CONCLUSION: ePVS from Duarte's formula was associated with congestion status and improved risk stratification regardless of renal function. Our findings suggest that Duarte-derived ePVS is a useful congestion variable in patients with HFpEF.

4.
Eur Heart J ; 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32118256

RESUMO

AIMS: The described association of low diastolic blood pressure (DBP) with increased cardiovascular outcomes could be due to reduced coronary perfusion or is simply due to reverse causation. If DBP is physiologically relevant, coronary reperfusion after myocardial infarction (MI) might influence DBP-risk association. METHODS AND RESULTS: The relation of achieved DBP with cardiovascular death or cardiovascular hospitalization, cardiovascular death, and all-cause death was explored in 5929 patients after acute myocardial infarction (AMI) with impaired left ventricular function, signs and symptoms of heart failure, or diabetes in the EPHESUS trial according to their reperfusion status. Cox regression models were used to assess the impact of reperfusion status on the association of DBP and systolic blood pressure (SBP) with outcomes in an adjusted fashion. In patients without reperfusion, lower DBP <70 mmHg was associated with increased risk for all-cause death [adjusted hazard ratios (HRs) 1.80, 95% confidence interval (CI) 1.41-2.30; P < 0.001], cardiovascular death (HR 1.70, 95% CI 1.3-3.22; P < 0.001), cardiovascular death or cardiovascular hospitalization (HR 1.54, 95% CI 1.26-1.87; P < 0.001). In patients with reperfusion, the risk increase at low DBP was not observed. At low SBP, risk increased independently of reperfusion. A sensitivity analysis in the subgroup of patients with optimal SBP of 120-130 mmHg showed again risk reduction of reperfusion at low DBP. Adding the treatment allocation to eplerenone or placebo into the models had no effects on the results. CONCLUSION: Patients after AMIs with a low DBP had an increased risk, which was sensitive to reperfusion therapy. Low blood pressure after MI identifies in patients with particular higher risk. These data support the hypothesis that low DBP in patients with stenotic coronary lesions is associated with risk, potentially involving coronary perfusion pressure and the recommendations provided by guidelines suggesting lower DBP boundaries for these high-risk patients.

5.
Eur J Heart Fail ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32077220

RESUMO

AIMS: Women with heart failure (HF) are under-represented in individual randomized clinical trials (RCTs). Little is known about sex-specific treatment effects in HF medications. We evaluated sex differences in the response to mineralocorticoid receptor antagonists (MRAs) in major HF MRA trials, including a broad spectrum of left ventricular ejection fraction (LVEF). METHODS AND RESULTS: Individual patient data fixed-effect meta-analysis was performed using 6167 patients (31.4% were women) recruited in three placebo-controlled RCTs: Randomized Aldactone Evaluation Study (RALES), Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) and Spironolactone for Heart Failure with Preserved Ejection Fraction (TOPCAT)-Americas. Compared to men, women were older, had higher body mass index and lower glomerular filtration rate. They also had higher LVEF and poorer New York Heart Association functional class and were less likely to be taking angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers. Placebo-arm event rates were lower for women compared with men (15.4 vs. 22.1 per 100 person-year; P = 0.002). MRAs reduced consistently, in men and women, the relative risk for cardiovascular death or HF hospitalization (P for interaction = 0.83), cardiovascular death (P for interaction = 0.44) and all-cause death (P for interaction = 0.19). These findings remained consistent after adjustment for potential confounders, regardless of LVEF. There was no sex-specific impact of MRA on the rate of hyperkalaemia and worsening renal function during the median 22 months of follow-up. CONCLUSION: In three large MRA RCTs, women were substantially different from men with regard to their clinical features and event rates. Nonetheless, this meta-analysis supports a consistent and beneficial MRA effect regardless of sex.

6.
Eur J Heart Fail ; 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32078214

RESUMO

AIMS: Hyperkalaemia and hypokalaemia are common in heart failure and associated with worse outcomes. However, the optimal potassium range is unknown. We sought to determine the optimal range of potassium in patients with heart failure and reduced ejection fraction (< 40%) by exploring the relationship between baseline potassium level and short- and long-term outcomes using the Swedish Heart Failure Registry from 1 January 2006 to 31 December 2012. METHODS AND RESULTS: We assessed the association between baseline potassium level and all-cause mortality at 30 days, 12 months, and maximal follow-up, in uni- and multivariable stratified and restricted cubic spline Cox regressions. Of 13 015 patients, 93.3% had potassium 3.5-5.0 mmol/L, 3.7% had potassium <3.5 mmol/L, and 3.0% had potassium >5.0 mmol/L. Potassium <3.5 mmol/L and >5.0 mmol/L were more common with lower estimated glomerular filtration rate and heart failure of longer duration and greater severity. The potassium level associated with the lowest hazard risk for mortality at 30 days, 12 months, and maximal follow-up was 4.2 mmol/L, and there was a steep increase in risk with both higher and lower potassium levels. In adjusted strata analyses, lower potassium was independently associated with all-cause mortality at 12 months and maximal follow-up, while higher potassium levels only increased risk at 30 days. CONCLUSION: In this nationwide registry, the relationship between potassium and mortality was U-shaped, with an optimal potassium value of 4.2 mmol/L. After multivariable adjustment, hypokalaemia was associated with increased long-term mortality but hyperkalaemia was associated with increased short-term mortality.

7.
JACC Heart Fail ; 8(3): 188-198, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31926854

RESUMO

OBJECTIVES: The purpose of this study was to investigate the effects of mineralocorticoid receptor antagonists (MRAs) on systolic blood pressure (SBP) and outcomes according to baseline SBP in patients with heart failure with reduced ejection fraction (HFrEF). BACKGROUND: MRAs are greatly underused in patients with HFrEF, often because of fear of adverse events. Concern about hypotension has been raised by the demonstration that MRAs are particularly effective treatment for resistant hypertension. METHODS: The effect of MRA therapy was studied in 4,396 patients with HFrEF randomized in the RALES (Randomized Aldactone Evaluation Study) and EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) trials. RESULTS: Mean SBP change from baseline to 6 months was +1.4 ± 18.1 mm Hg in the placebo group and -1.2 ± 17.9 mm Hg in the MRA group. The between-treatment difference was 2.6 mm Hg (95% confidence interval [CI]: 1.5 to 3.6; p < 0.001). All outcomes were reduced by MRA therapy overall, with consistent effects across SBP categories (e.g., all-cause mortality, overall hazard ratio [HR] of 0.72; 95% CI: 0.64 to 0.82; p < 0.001; SBP ≤105 mm Hg; HR: 0.72; 95% CI: 0.56 to 0.94; SBP >105 to ≤115 mm Hg; HR: 0.78; 95% CI: 0.60 to 1.02; SBP >115 to ≤125 mm Hg; HR: 0.71; 95% CI: 0.53 to 0.94; SBP >125 to ≤135 mm Hg; HR: 0.79; 95% CI: 0.57 to 1.10; and SBP > 135 mm Hg; HR: 0.67; 95% CI: 0.50 to 0.90; p for interaction = 0.95). Hypotension was infrequent and not more common with MRA therapy than with placebo, overall (4.6% vs. 3.9%; p = 0.25) or in any SBP category. CONCLUSIONS: MRA treatment had little effect on SBP in patients with HFrEF, and the clinical benefits were not modified by baseline SBP. MRA treatment infrequently caused hypotension, even when the baseline SBP was low. The treatment discontinuation rates between MRA and placebo therapy were similar. Low SBP is not a reason to withhold MRA therapy in patients with HFrEF.

8.
Eur J Heart Fail ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919958

RESUMO

BACKGROUND: To assess the prognostic value of mineralocorticoid receptor antagonist (MRA) initiation and change in serum potassium (K+ ) during follow-up in patients post-acute myocardial infarction with left ventricular dysfunction or chronic heart failure (HF) and reduced ejection fraction (HFrEF). METHODS AND RESULTS: Risk scores for predicting cardiovascular death (primary outcome), hospitalization for HF and all-cause death were developed. K+ and other relevant time-updated clinical and biological variables were added to conventional prognostic factors when constructing these new models. EPHESUS (n = 6632) was the derivation cohort, while EMPHASIS-HF (chronic HF, n = 2737) was used as external validation cohort. The final cardiovascular death risk score included medical history, clinical and biological parameters (e.g. K+ , below or above the normal range of 4-5 mmol/L, estimated glomerular filtration rate, and anaemia), as well as aspects of treatment (any diuretic usage, MRA use or discontinuation, and beta-blocker use). The risk score performed well in both the derivation and validation cohorts and outperformed the MAGGIC score. A web-based calculator was created to allow easy determination of the risk score (http://cic-p-nancy.fr/CardiovascularriskscoreCalculator/). CONCLUSION: Adding time-updated variables, including K+ and MRA treatment, improved risk prediction of cardiovascular death (on top of the MAGGIC score) in patients with HF eligible for renin-angiotensin system inhibitors and MRA therapy. This new risk score including MRA usage and K+ may be of value in helping physicians to better use MRAs, avoid unnecessary and potentially detrimental permanent discontinuations, and therefore improving cardiovascular outcomes in patients with chronic HFrEF or HF after acute myocardial infarction with left ventricular dysfunction.

9.
Circ Heart Fail ; 13(1): e006638, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31957468

RESUMO

BACKGROUND: Spironolactone has been demonstrated to reduce heart failure (HF) hospitalization in patients with HF with preserved ejection fraction in the Americas region of the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial). We assessed effects of 12 months of treatment with spironolactone on biomarkers reflecting myocardial stress, myocardial injury, renal function, and systemic inflammation. METHODS: This TOPCAT biorepository substudy evaluated 247 patients (14% of the total 1767 patients in the Americas region) with symptomatic HF, ejection fraction ≥45%, and elevated natriuretic peptides or a prior HF hospitalization. Paired blood samples at baseline and after 12 months of treatment with spironolactone or placebo were available in 204 patients. RESULTS: At baseline, the median (interquartile range) concentration of BNP (B-type natriuretic peptide) was 124 (69-197) ng/L, NT-proBNP (N-terminal-pro-B-type natriuretic peptide) 624 (307-1312) ng/L, hs-cTnI (high sensitivity cardiac troponin I) 6.3 (3.4-13.0) ng/L, hs-CRP (high sensitivity C-reactive protein) 2.8 (1.3-6.1) mg/L, uric acid 7.2 (5.8-8.7) mg/dL, and urine protein-creatinine ratio 0.11 (0.08-0.20) mg/mg. Compared with placebo-assigned participants at 12 months, those randomized to spironolactone experienced greater reductions from baseline in levels of NT-proBNP (P=0.017) and BNP (P=0.002); these differences persisted after adjustment for demographics, comorbidities, estimated glomerular filtration rate, and enrollment strata. No between-group differences in changes in hs-cTnI, CRP, uric acid, or urine protein-creatinine ratio were observed. CONCLUSIONS: This TOPCAT biorepository substudy suggests potential effects on markers of cardiac wall stress or filling pressures during 12 months of treatment with spironolactone in patients with chronic HF with preserved ejection fraction. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00094302.

10.
Eur J Heart Fail ; 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31944496

RESUMO

AIMS: To develop a risk model for sudden cardiac death (SCD) in high-risk acute myocardial infarction (AMI) survivors. METHODS AND RESULTS: Data from the Effect of Carvedilol on Outcome After Myocardial Infarction in Patients With Left Ventricular Dysfunction trial (CAPRICORN) and the Valsartan in Acute Myocardial Infarction Trial (VALIANT) were used to create a SCD risk model (with non-SCD as a competing risk) in 13 202 patients. The risk model was validated in the Eplerenone Post-AMI Heart Failure Efficacy and Survival Study (EPHESUS). The rate of SCD was 3.3 (95% confidence interval 3.0-3.5) per 100 person-years over a median follow-up of 2.0 years. Independent predictors of SCD included age > 70 years; heart rate ≥ 70 bpm; smoking; Killip class III/IV; left ventricular ejection fraction ≤30%; atrial fibrillation; history of prior myocardial infarction, heart failure or diabetes; estimated glomerular filtration rate < 60 mL/min/1.73 m2 ; and no coronary reperfusion or revascularisation therapy for index AMI. The model was well calibrated and showed good discrimination (C-statistic = 0.72), including in the early period after AMI. The observed 2-year event rates increased steeply with each quintile of risk score (1.9%, 3.6%, 6.2%, 9.0%, 13.4%, respectively). CONCLUSION: An easy to use SCD risk score developed from routinely collected clinical variables in patients with heart failure, left ventricular systolic dysfunction or both, early after AMI was superior to left ventricular ejection fraction. This score might be useful in identifying patients for future trials testing treatments to prevent SCD early after AMI.

11.
J Hypertens ; 38(3): 420-425, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31584516

RESUMO

BACKGROUND: Visit-to-visit office blood pressure (BP) variability (BPV) has been associated with morbidity and mortality outcomes in several cardiovascular conditions. The aim of this study was to evaluate the association between BPV and outcomes in patients with heart failure and reduced ejection fraction and the effect of eplerenone on BPV. METHODS AND RESULTS: We evaluated the associations between BPV, calculated as SBP coefficient of variation (SBP-CoV = SD/mean × 100%), and the primary composite endpoint of cardiovascular mortality or heart failure hospitalization (HFH), and its components, in 2549 patients from the Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms trial. Lower SBP-CoV was independently associated with a higher risk of all the studied outcomes, while higher as well as lower SBP-CoV were associated with a higher risk of cardiovascular death. After a median follow-up period of 21 months the risk of the composite outcome of cardiovascular death or HFH was almost double in the lower SBP-CoV tertile as compared with the intermediate tertile [adjusted hazard ratio: 2.01, 95% confidence interval (1.62-2.51), P < 0.001]. The relationship between SBP-CoV and outcomes was not modified by eplerenone (P value for interaction = 0.48). An interaction was detected between mean SBP and SBP-CoV for the primary outcome (P = 0.048) and for HFH (P = 0.018). The effect modification was slight, but lower SBP-CoV was associated with worse outcomes in patients with both low and high SBP, while this interaction was less clear for patients with SBP in the 'normal' range. CONCLUSION: In our patients with heart failure and reduced ejection fraction and mild symptoms, both a lower and higher SBP-CoV were associated with worse outcomes. SBP-CoV did not modify the benefit of eplerenone. Further studies are warranted to clarify the role of BPV in heart failure. CLINICALTRIALS. GOV IDENTIFIER: NCT00232180.

12.
Am J Med ; 133(2): e25-e31, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31401165

RESUMO

BACKGROUND: In the Studies of Left Ventricular Dysfunction (SOLVD) treatment trial, similar clinical benefits were observed between starting doses of enalapril and the target dose achieved by postrandomization up-titration. In our current analysis, protecting the randomization, we examined the early effects of starting doses of enalapril. METHODS: There were 2569 patients with mild-to-moderate chronic heart failure with reduced ejection fraction (ejection fraction ≤35%) randomized to receive starting doses (5-10 mg/day) of placebo (n = 1284) or enalapril (n = 1285). At day 14, both study drugs were blindly up-titrated to the target dose (20 mg/day). Overall, 96% (2458/2569) of the patients returned for dose up-titration, which was achieved in 59% (1444/2458), 48% (696/1444) of whom were in the enalapril group. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes in the enalapril group were estimated. RESULTS: HRs (95% CIs) for all-cause mortality, heart failure hospitalization, and the combined endpoint of heart failure hospitalization or all-cause mortality at 14 days after randomization were 0.80 (0.32-2.03), 0.63 (0.35-1.12), and 0.65 (0.39-1.06), respectively. Corresponding HRs (95% CIs) at 30 days were 0.82 (0.41-1.67), 0.43 (0.27-0.68), and 0.43 (0.27-0.68), respectively. The magnitude of these early effects of starting doses of enalapril is similar to its previously reported long-term effects at the target dose. CONCLUSION: These data suggest that in stable ambulatory patients with heart failure with reduced ejection fraction, the magnitude of the early effect of starting doses of enalapril is similar to that observed during longer-term therapy with the target doses of the drug.

13.
Clin Res Cardiol ; 109(2): 194-204, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31250134

RESUMO

INTRODUCTION: After myocardial infarction complicated by heart failure or diabetes, eplerenone (compared to placebo) significantly decreases amino-terminal propeptide of type III procollagen (PIIINP). Determining the subset of patients who are more prone to have a decrease in PIIINP and those who may respond better to the anti-fibrotic effects of mineralocorticoid receptor antagonists (MRA) therapy may be relevant for a personalized treatment approach. The aim of this study is to identify predictors of a PIIINP decrease and assess potential subgroups of "responders" to eplerenone. METHODS: Clinical factors and biomarkers were evaluated as predictors of a PIIINP decrease from randomization to month 9 in 323 patients from the biomarker substudy of Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Additionally, the association between PIIINP decrease and the composite of cardiovascular (CV) death or CV hospitalization were also explored. External validation was performed in the REMINDER trial. RESULTS: Female sex, eplerenone, reperfusion therapy, potassium < 4 mmol/L, circulating levels of PIIINP ≥ 3.6 ng/mL and PINP ≥ 27 ng/mL predicted a PIIINP decrease (AUC = 0.75). Randomization PIIINP showed a significant interaction with the treatment allocation: patients with PIIINP ≥ 3.6 ng/mL had a better response (decrease in PIIINP) to eplerenone (OR for PIIINP ≥ 3.6 = 2.9, 95% CI 1.46-5.89, p = 0.003) and OR for PIIINP < 3.6 = 1.09, 95% CI 0.55-2.2, p = 0.8; interactionp = 0.026). These findings were internally robust using another statistical approach (LOESS). External validation showed good discrimination (AUC = 0.70). There was a tendency toward a lower rate of CV death/CV hospitalizations in patients with decreased PIIINP (adjusted HR = 0.52, 95% CI 0.26-1.02, p = 0.058). CONCLUSION: In patients who had a myocardial infarction, clinical factors used in combination and treatment with eplerenone were associated with a PIIINP decrease. Interestingly, higher randomization PIIINP levels might help in identifying patients more prone to have an "anti-fibrotic response" when treated with MRAs. Predictors of an antifibrotic response after MI complicated by HF. Several clinical factors and biomarkers predicted a PIIINP decrease after an MI complicated by HF. There was a significant interaction between baseline PIIINP levels and eplerenone treatment: patients with baseline PIIINP ≥ 3.6 mmol/L treated with eplerenone had the best response (PIIINP decrease).

14.
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.

15.
Circ Heart Fail ; 12(12): e006539, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31813280

RESUMO

BACKGROUND: To describe characteristics and outcomes in women and men with heart failure with preserved ejection fraction. METHODS: Baseline characteristics (including biomarkers and quality of life) and outcomes (primary outcome: composite of first heart failure hospitalization or cardiovascular death) were compared in 4458 women and 4010 men enrolled in CHARM-Preserved (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) (EF≥45%), I-Preserve (Irbesartan in heart failure with Preserved ejection fraction), and TOPCAT-Americas (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial). RESULTS: Women were older and more often obese and hypertensive but less likely to have coronary artery disease or atrial fibrillation. Women had more symptoms and signs of congestion and worse quality of life. Despite this, the risk of the primary outcome was lower in women (hazard ratio, 0.80 [95% CI, 0.73-0.88]), as was the risk of cardiovascular death (hazard ratio, 0.70 [95% CI, 0.62-0.80]), but there was no difference in the rate for first hospitalization for heart failure (hazard ratio, 0.92 [95% CI, 0.82-1.02]). The lower risk of cardiovascular death in women, compared with men, was in part explained by a substantially lower risk of sudden death (hazard ratio, 0.53 [0.43-0.65]; P<0.001). E/A ratio was lower in women (1.1 versus 1.2). CONCLUSIONS: There are significant differences between women and men with heart failure with preserved ejection fraction. Despite worse symptoms, more congestion, and lower quality of life, women had similar rates of hospitalization and better survival than men. Their risk of sudden death was half that of men. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00853658, NCT01035255.

16.
Am Heart J ; 218: 66-74, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31707330

RESUMO

BACKGROUND: Analyses of country or regional differences in cardiovascular (CV) trials are based on geographical subgroup analyses. However, apart from map location and related racial, ethnic, and genetic variations, identified differences may also depend on social structure and provision and access to health care, for which country income and income inequality are indicators. The aim of the study was to examine the association between country per capita income and income inequality and prognosis in patients with heart failure or an acute coronary syndrome in 3 international trials (EMPHASIS-HF, EPHESUS, and EXAMINE). METHODS: Countries were classified into high income or low-middle income (LMICs) and into low, middle, or high inequality using the Gini index. The main outcome measures were all-cause and CV death. RESULTS: Patients from LMICs and countries with higher inequality were younger, were less often white, had fewer comorbid conditions, and were less often treated with guideline-recommended therapies, including devices. These patients had higher adjusted mortality rates (+15% to +70%) compared with patients from high-income countries and countries with less inequality. Patients from countries with the combination of greater inequality and low-middle income had particularly high mortality rates (+80% to +190%) compared with those that did not have both characteristics. Living in a country that is poor and has inequality had more impact on death rates than any comorbidity. These findings were reproduced in 3 trials. CONCLUSIONS: Patients from LMICs and countries with greater inequality had the highest mortality rates. The prognostic impact of income and inequality is substantial and should be considered when looking into subgroup differences in CV trials.

18.
JACC Heart Fail ; 7(12): 1012-1021, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31779922

RESUMO

OBJECTIVES: This study sought to assess the effect of MRA treatment (vs. placebo) in older patients (≥75 years of age) compared with younger patients (<75 years of age) with heart failure (HF). BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) have been shown to reduce morbidity and mortality in patients with HF with reduced ejection fraction (HFrEF) and in a subset of patients with HF with preserved EF (HFpEF). Notwithstanding, MRAs are underused, especially in the elderly. Pooling the individual patient data (IPD) provided more statistical power with which to assess the efficacy and safety of MRA treatment in this subpopulation. METHODS: An IPD meta-analysis was performed using Cox proportional hazards models stratified by trial. A total of 1,756 patients (853 randomized to placebo and 903 to MRA) ≥75 years of age, along with 4,411 patients (2,242 randomized to placebo and 2,169 to MRA) <75 years of age were included. The primary outcome was a composite of death from cardiovascular causes or hospitalization for HF. RESULTS: The treatment groups were well balanced. Patients ≥75 years of age or older and those 80 years of age, 61% were male, 30% had diabetes, and the mean estimated glomerular filtration rate 59 ml/min. The primary outcome occurred in 331 patients (38.8%) in the placebo group versus 281 (31.1%) in the MRA group (hazard ratio: 0.74; 95% confidence interval: 0.63 to 0.86; p < 0.001; and the heterogeneity p value [heterogeneity p = Cochran's Q p value of treatment effect by study interaction] was 0.52). Cardiovascular death and all-cause death were also reduced by MRAs without significant between-trial or age (younger vs. older) heterogeneity. Worsening renal function and hyperkalemia occurred more frequently in patients taking MRAs (vs. placebo). Compared to younger patients, worsening renal function (but not hyperkalemia) was found more frequently in the elderly. CONCLUSIONS: MRAs reduced morbidity and mortality in elderly patients with HF, a beneficial effect that is more marked in patients with HFrEF but homogenous across HFrEF and HFpEF. Implementation of measures that increase MRA treatment in this population are warranted.

19.
JACC Heart Fail ; 7(12): 1022-1028, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31779923

RESUMO

OBJECTIVES: The authors examined efficacy and safety of spironolactone by age in the Americas region (N = 1,767) of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial. BACKGROUND: Heart failure with preserved ejection fraction disproportionately affects older adults who may exhibit changes in physiology and variable pharmacokinetics. METHODS: TOPCAT enrolled patients with heart failure and a left ventricular ejection fraction ≥45% who were age 50 or older with an estimated glomerular filtration rate ≥30 mL/min/1.73 m2 and prior heart failure hospitalization or elevated natriuretic peptide levels. Participants were randomized to spironolactone or placebo with a mean follow-up duration of 3.3 years. We assessed treatment effect and safety by protocol-defined age categories (<65, 65 to 74, and ≥75 years). RESULTS: The mean age was 72 ± 10 years (range 50 to 97 years) with 41% over the age of 75 years. Participants ≥75 years were more commonly women and white and had a lower body mass index and estimated glomerular filtration rate compared with the younger age categories. Spironolactone reduced the primary composite outcome compared with placebo across all age categories (p interaction = 0.42). However, spironolactone was associated with an increased risk of the safety endpoint (hazard ratio: 2.54; 95% confidence interval: 1.91 to 3.37; p < 0.001), particularly in older age groups (p interaction = 0.02). Findings in the whole TOPCAT cohort were consistent with results from the Americas region. CONCLUSIONS: In this post hoc, exploratory analysis of the TOPCAT trial data from the Americas region, although there was no effect of age on efficacy, there were considerable effects of age on increased rates of adverse safety outcomes. These results should be weighed when considering spironolactone for older heart failure with preserved ejection fraction patients. (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist [TOPCAT]; NCT00094302).

20.
Am J Nephrol ; 50(5): 333-344, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31655812

RESUMO

BACKGROUND: Among diabetics, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality, and progression of their underlying disease. Finerenone is a novel, non-steroidal, selective mineralocorticoid-receptor antagonist which has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD), while revealing only a low risk of hyperkalemia. However, the effect of finerenone on renal and CV outcomes has not been investigated in long-term trials yet. METHODS: The Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease -(FIDELIO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important renal and CV outcomes in T2D patients with CKD. FIDELIO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 5.5 years. FIDELIO-DKD randomized 5,734 patients with an estimated glomerular filtration rate (eGFR) ≥25-<75 mL/min/1.73 m2 and albuminuria (urinary albumin-to-creatinine ratio ≥30-≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of kidney failure, a sustained decrease of eGFR ≥40% from baseline over at least 4 weeks, or renal death. CONCLUSION: FIDELIO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of renal and CV events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen.

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