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      Management of low blood pressure in ambulatory heart failure with reduced ejection fraction patients

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          Abstract

          Low blood pressure is common in patients with heart failure and reduced ejection fraction (HFrEF). While spontaneous hypotension predicts risk in HFrEF, there is only limited evidence regarding the relationship between hypotension observed during heart failure (HF) drug titration and outcome. Nevertheless, hypotension (especially orthostatic hypotension) is an important factor limiting the titration of HFrEF treatments in routine practice. In patients with signs of shock and/or severe congestion, hospitalization is advised. However, in the very frequent cases of non‐severe and asymptomatic hypotension observed while taking drugs with a class I indication in HFrEF, European and US guidelines recommend maintaining the same drug dosage. In instances of symptomatic or severe persistent hypotension (systolic blood pressure < 90 mmHg), it is recommended to first decrease blood pressure reducing drugs not indicated in HFrEF as well as the loop diuretic dose in the absence of associated signs of congestion. Unless the management of hypotension appears urgent, a HF specialist should then be sought rather than stopping or decreasing drugs with a class I indication in HFrEF. If symptoms or severe hypotension persist, no recommendations exist. Our HF group reviewed available evidence and proposes certain steps to follow in such situations in order to improve the pharmacological management of these patients.

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          Most cited references43

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          Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure

          We compared the angiotensin receptor-neprilysin inhibitor LCZ696 with enalapril in patients who had heart failure with a reduced ejection fraction. In previous studies, enalapril improved survival in such patients. In this double-blind trial, we randomly assigned 8442 patients with class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either LCZ696 (at a dose of 200 mg twice daily) or enalapril (at a dose of 10 mg twice daily), in addition to recommended therapy. The primary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure, but the trial was designed to detect a difference in the rates of death from cardiovascular causes. The trial was stopped early, according to prespecified rules, after a median follow-up of 27 months, because the boundary for an overwhelming benefit with LCZ696 had been crossed. At the time of study closure, the primary outcome had occurred in 914 patients (21.8%) in the LCZ696 group and 1117 patients (26.5%) in the enalapril group (hazard ratio in the LCZ696 group, 0.80; 95% confidence interval [CI], 0.73 to 0.87; P<0.001). A total of 711 patients (17.0%) receiving LCZ696 and 835 patients (19.8%) receiving enalapril died (hazard ratio for death from any cause, 0.84; 95% CI, 0.76 to 0.93; P<0.001); of these patients, 558 (13.3%) and 693 (16.5%), respectively, died from cardiovascular causes (hazard ratio, 0.80; 95% CI, 0.71 to 0.89; P<0.001). As compared with enalapril, LCZ696 also reduced the risk of hospitalization for heart failure by 21% (P<0.001) and decreased the symptoms and physical limitations of heart failure (P=0.001). The LCZ696 group had higher proportions of patients with hypotension and nonserious angioedema but lower proportions with renal impairment, hyperkalemia, and cough than the enalapril group. LCZ696 was superior to enalapril in reducing the risks of death and of hospitalization for heart failure. (Funded by Novartis; PARADIGM-HF ClinicalTrials.gov number, NCT01035255.).
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            The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators.

            Aldosterone is important in the pathophysiology of heart failure. In a doubleblind study, we enrolled 1663 patients who had severe heart failure and a left ventricular ejection fraction of no more than 35 percent and who were being treated with an angiotensin-converting-enzyme inhibitor, a loop diuretic, and in most cases digoxin. A total of 822 patients were randomly assigned to receive 25 mg of spironolactone daily, and 841 to receive placebo. The primary end point was death from all causes. The trial was discontinued early, after a mean follow-up period of 24 months, because an interim analysis determined that spironolactone was efficacious. There were 386 deaths in the placebo group (46 percent) and 284 in the spironolactone group (35 percent; relative risk of death, 0.70; 95 percent confidence interval, 0.60 to 0.82; P<0.001). This 30 percent reduction in the risk of death among patients in the spironolactone group was attributed to a lower risk of both death from progressive heart failure and sudden death from cardiac causes. The frequency of hospitalization for worsening heart failure was 35 percent lower in the spironolactone group than in the placebo group (relative risk of hospitalization, 0.65; 95 percent confidence interval, 0.54 to 0.77; P<0.001). In addition, patients who received spironolactone had a significant improvement in the symptoms of heart failure, as assessed on the basis of the New York Heart Association functional class (P<0.001). Gynecomastia or breast pain was reported in 10 percent of men who were treated with spironolactone, as compared with 1 percent of men in the placebo group (P<0.001). The incidence of serious hyperkalemia was minimal in both groups of patients. Blockade of aldosterone receptors by spironolactone, in addition to standard therapy, substantially reduces the risk of both morbidity and death among patients with severe heart failure.
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              Eplerenone in patients with systolic heart failure and mild symptoms.

              Mineralocorticoid antagonists improve survival among patients with chronic, severe systolic heart failure and heart failure after myocardial infarction. We evaluated the effects of eplerenone in patients with chronic systolic heart failure and mild symptoms. In this randomized, double-blind trial, we randomly assigned 2737 patients with New York Heart Association class II heart failure and an ejection fraction of no more than 35% to receive eplerenone (up to 50 mg daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure. The trial was stopped prematurely, according to prespecified rules, after a median follow-up period of 21 months. The primary outcome occurred in 18.3% of patients in the eplerenone group as compared with 25.9% in the placebo group (hazard ratio, 0.63; 95% confidence interval [CI], 0.54 to 0.74; P<0.001). A total of 12.5% of patients receiving eplerenone and 15.5% of those receiving placebo died (hazard ratio, 0.76; 95% CI, 0.62 to 0.93; P=0.008); 10.8% and 13.5%, respectively, died of cardiovascular causes (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P=0.01). Hospitalizations for heart failure and for any cause were also reduced with eplerenone. A serum potassium level exceeding 5.5 mmol per liter occurred in 11.8% of patients in the eplerenone group and 7.2% of those in the placebo group (P<0.001). Eplerenone, as compared with placebo, reduced both the risk of death and the risk of hospitalization among patients with systolic heart failure and mild symptoms. (Funded by Pfizer; ClinicalTrials.gov number, NCT00232180.).
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                Author and article information

                Contributors
                n.girerd@chu-nancy.fr
                Journal
                Eur J Heart Fail
                Eur J Heart Fail
                10.1002/(ISSN)1879-0844
                EJHF
                European Journal of Heart Failure
                John Wiley & Sons, Ltd. (Oxford, UK )
                1388-9842
                1879-0844
                30 April 2020
                August 2020
                30 April 2020
                : 22
                : 8 ( doiID: 10.1002/ejhf.v22.8 )
                : 1357-1365
                Affiliations
                [ 1 ] Heart Failure and Valvular Heart Diseases Unit, Department of Cardiology Mediterranean University Cardio‐Oncology Center (MEDI‐CO Center), Hôpital Nord, Aix‐Marseille I University Marseille France
                [ 2 ] Cardiology Department Hôpital Sainte Musse Toulon France
                [ 3 ] CUMR‐S 942 MASCOT Paris University, Cardiology Department, Hôpital Lariboisière, Assistance Publique Hôpitaux de Paris Paris France
                [ 4 ] Cardiology Department Centre Hospitalier d'Antibes Juan les Pins Antibes France
                [ 5 ] Cardio‐Thoracic Surgery Department Hôpital de la Timone Marseille France
                [ 6 ] Cardiology Department Centre Hospitalier de Cannes Cannes France
                [ 7 ] Cardiology Division Massachusetts General Hospital, Baim Institute for Clinical Research, Harvard Medical School Boston MA USA
                [ 8 ] PhyMedExp, Université de Montpellier, INSERM, CNRS, Cardiology Department, CHU de Montpellier France
                [ 9 ] Faculté de Médecine Université de Lorraine, Centre d'Investigations Cliniques Plurithématique 1433, Institut Lorrain du Cœur et des Vaisseaux, Vandoeuvre les Nancy France Groupe choc, INSERM U1116 Vandoeuvre les Nancy France
                [ 10 ] F‐CRIN INI‐CRCT (Cardiovascular and Renal Clinical Trialists) Nancy France
                [ 11 ] Cardiology Department Institut Lorrain du Cœur et des Vaisseaux, CHRU Nancy Nancy France
                Author notes
                [*] [* ] Corresponding author. Centre d'Investigations Cliniques‐INSERM CHU de Nancy, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu, 4 rue du Morvan, 54500 Vandoeuvre Lès Nancy, France. Tel: +33 3 83157320, Fax: +33 3 83157324, Email: n.girerd@ 123456chu-nancy.fr

                [†]

                Co‐first authors.

                Article
                EJHF1835
                10.1002/ejhf.1835
                7540603
                32353213
                3cf4fe37-70d2-4a56-8e4a-556a99786563
                © 2020 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 13 December 2019
                : 06 April 2020
                : 08 April 2020
                Page count
                Figures: 2, Tables: 0, Pages: 9, Words: 6572
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                August 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.2 mode:remove_FC converted:07.10.2020

                Cardiovascular Medicine
                hypotension,heart failure,beta‐blocker,angiotensin‐converting enzyme inhibitor,angiotensin receptor blocker,angiotensin receptor–neprilysin inhibitor,mineralocorticoid receptor antagonist,diuretics

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