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      Significance of Ischemic Heart Disease in Patients With Heart Failure and Preserved, Midrange, and Reduced Ejection Fraction : A Nationwide Cohort Study

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          Abstract

          The pathogenic role of ischemic heart disease (IHD) in heart failure (HF) with reduced ejection fraction (HFrEF; EF <40%) is well established, but its pathogenic and prognostic significance in HF with midrange (HFmrEF; EF 40%-50%) and preserved EF (HFpEF; EF ≥50%) has been much less explored.

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          Most cited references 31

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          The perindopril in elderly people with chronic heart failure (PEP-CHF) study.

          Many patients who receive a diagnosis of heart failure have neither a low left ventricular (LV) ejection fraction nor valve disease. Few substantial randomized controlled trials have been conducted in this population, none has focussed on patients with evidence of diastolic dysfunction and none has shown clear benefit on symptoms, morbidity, or mortality. This was a randomized double-blind trial, comparing placebo with perindopril, 4 mg/day in patients aged > or =70 years with a diagnosis of heart failure, treated with diuretics and an echocardiogram suggesting diastolic dysfunction and excluding substantial LV systolic dysfunction or valve disease. The primary endpoint was a composite of all-cause mortality and unplanned heart failure related hospitalization with a minimum follow-up of 1 year. A total of 850 patients were randomized. Their mean age was 76 (SD 5) years and 55% were women. Median follow-up was 2.1 (IQR 1.5-2.8) years. Enrollment and event rates were lower than anticipated, reducing the power of the study to show a difference in the primary endpoint to 35%. Many patients withdrew from perindopril (28%) and placebo (26%) after 1 year and started taking open-label ACE-inhibitors. Overall, 107 patients assigned to placebo and 100 assigned to perindopril reached the primary endpoint (HR 0.919: 95% CI 0.700-1.208; P = 0.545). By 1 year, reductions in the primary outcome (HR 0.692: 95% CI 0.474-1.010; P = 0.055) and hospitalization for heart failure (HR 0.628: 95% CI 0.408-0.966; P = 0.033) were observed and functional class (P < 0.030) and 6-min corridor walk distance (P = 0.011) had improved in those assigned to perindopril. Uncertainty remains about the effects of perindopril on long-term morbidity and mortality in this clinical setting since this study had insufficient power for its primary endpoint. However, improved symptoms and exercise capacity and fewer hospitalizations for heart failure in the first year were observed on perindopril, during which most patients were on assigned therapy, suggesting that it may be of benefit in this patient population.
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            Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial.

            Large observational studies, small prospective studies and post-hoc analyses of randomised clinical trials have suggested that statins could be beneficial in patients with chronic heart failure. However, previous studies have been methodologically weak. We investigated the efficacy and safety of the statin rosuvastatin in patients with heart failure. We undertook a randomised, double-blind, placebo-controlled trial in 326 cardiology and 31 internal medicine centres in Italy. We enrolled patients aged 18 years or older with chronic heart failure of New York Heart Association class II-IV, irrespective of cause and left ventricular ejection fraction, and randomly assigned them to rosuvastatin 10 mg daily (n=2285) or placebo (n=2289) by a concealed, computerised telephone randomisation system. Patients were followed up for a median of 3.9 years (IQR 3.0-4.4). Primary endpoints were time to death, and time to death or admission to hospital for cardiovascular reasons. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00336336. We analysed all randomised patients. 657 (29%) patients died from any cause in the rosuvastatin group and 644 (28%) in the placebo group (adjusted hazard ratio [HR] 1.00 [95.5% CI 0.898-1.122], p=0.943). 1305 (57%) patients in the rosuvastatin group and 1283 (56%) in the placebo group died or were admitted to hospital for cardiovascular reasons (adjusted HR 1.01 [99% CI 0.908-1.112], p=0.903). In both groups, gastrointestinal disorders were the most frequent adverse reaction (34 [1%] rosuvastatin group vs 44 [2%] placebo group). Rosuvastatin 10 mg daily did not affect clinical outcomes in patients with chronic heart failure of any cause, in whom the drug was safe.
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              Trends in patients hospitalized with heart failure and preserved left ventricular ejection fraction: prevalence, therapies, and outcomes.

              Heart failure with preserved ejection fraction (EF) is a common syndrome, but trends in treatments and outcomes are lacking. We analyzed data from 275 hospitals in Get With the Guidelines-Heart Failure from January 2005 to October 2010. Patients were stratified by EF as reduced EF (EF <40% [HF-reduced EF]), borderline EF (40%≤EF<50% [HF-borderline EF]), or preserved (EF ≥50% [HF-preserved EF]). Using multivariable models, we examined trends in therapies and outcomes. Among 110 621 patients, 50% (55 083) had HF-reduced EF, 14% (15 184) had HF-borderline EF, and 36% (40 354) had HF-preserved EF. From 2005 to 2010, the proportion of hospitalizations for HF-preserved EF increased from 33% to 39% (P<0.0001). In multivariable analyses, use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers at discharge decreased in all EF groups, and β-blocker use increased. Patients with HF-preserved EF less frequently achieved blood pressure control (adjusted odds ratio, 0.44 versus HF-reduced EF; P<0.001) and were more likely discharged to skilled nursing (adjusted odds ratio, 1.16 versus HF-reduced EF; P<0.001). In-hospital mortality for HF-preserved EF decreased from 3.32% in 2005 to 2.35% in 2010 (adjusted odds ratio, 0.89 per year; P=0.01) but was stable for patients with HF-reduced EF (3.03%-2.83%; adjusted odds ratio, 0.93 per year; P=0.10). Hospitalization for HF-preserved EF is increasing relative to HF-reduced EF. Although in-hospital mortality for patients with HF-preserved EF declined over the study period, an important opportunity remains for identifying evidence-based therapies in patients with HF-preserved EF.
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                Author and article information

                Journal
                Circulation: Heart Failure
                Circ Heart Fail
                Ovid Technologies (Wolters Kluwer Health)
                1941-3289
                1941-3297
                June 2017
                June 2017
                : 10
                : 6
                Affiliations
                [1 ]From the Department of Medical Sciences, Uppsala University and Uppsala Clinical Research Center, Sweden (O.V.); National Heart Centre Singapore (C.S.P.L., A.S.K., T.H.K.T., W.T.T.); Duke-NUS Medical School, Singapore (C.S.P.L., A.S.K.); Regional Cancer Centre Stockholm Gotland, Sweden (L.B.); School of Population Health, University of Western Australia, Perth (T.H.K.T.); Department of Cardiology, Skåne University Hospital, Lund University, Sweden (O.Ö.B.); Department of Medicine, Karolinska...
                Article
                10.1161/CIRCHEARTFAILURE.117.003875
                28615366
                © 2017

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