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      Hemodynamic effects of inotropic drugs in heart failure : A network meta-analysis of clinical trials

      review-article
      , MD a , , MD b , , MD a , , MD a , , MD a , , MD a ,
      Medicine
      Wolters Kluwer Health
      heart failure, hemodynamic, inotropic agent, network meta-analysis

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          Abstract

          Background:

          There is currently no consensus on the appropriate selection of inotropic therapy in ventricular dysfunction. The objective of the study was to detect the effects of different inotropes on the hemodynamics of patients who developed low cardiac output.

          Methods:

          PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched (all updated December 31, 2017). The inclusion criteria were as follows: low cardiac index (CI < 2.5 L/min/m 2) or New York Heart Association class II–IV, and at least 1 group receiving an inotropic drug compared to another group receiving a different inotropic/placebo treatment. The exclusion criteria were studies published as an abstract only, crossover studies, and studies with a lack of data on the cardiac index.

          Results:

          A total of 1402 patients from 37 trials were included in the study. Inotropic drugs were shown to increase the cardiac index (0.32, 95%CI:0.25, 0.38), heart rate (7.68, 95%CI:6.36, 9.01), and mean arterial pressure (3.17, 95%CI:1.96, 4.38) than the placebo. Overall, the pooled estimates showed no difference in terms of cardiac index, heart rate, mean arterial pressure, systemic vascular resistance, and mean pulmonary arterial pressure among the groups receiving different inotropes.

          Conclusions:

          Our systematic review found that inotrope therapy is not associated with the amelioration of hemodynamics. An accurate evaluation of the benefits and risks, and selection of the correct inotropic agent is required in all clinical settings.

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          Most cited references70

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          ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC.

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            The effect of digoxin on mortality and morbidity in patients with heart failure.

            (1997)
            The role of cardiac glycosides in treating patients with chronic heart failure and normal sinus rhythm remains controversial. We studied the effect of digoxin on mortality and hospitalization in a randomized, double-blind clinical trial. In the main trial, patients with a left ventricular ejection fraction of 0.45 or less were randomly assigned to digoxin (3397 patients) or placebo (3403 patients) in addition to diuretics and angiotensin-converting-enzyme inhibitors (median dose of digoxin, 0.25 mg per day; average follow-up, 37 months). In an ancillary trial of patients with ejection fractions greater than 0.45, 492 patients were randomly assigned to digoxin and 496 to placebo. In the main trial, mortality was unaffected. There were 1181 deaths (34.8 percent) with digoxin and 1194 deaths (35.1 percent) with placebo (risk ratio when digoxin was compared with placebo, 0.99; 95 percent confidence interval, 0.91 to 1.07; P=0.80). In the digoxin group, there was a trend toward a decrease in the risk of death attributed to worsening heart failure (risk ratio, 0.88; 95 percent confidence interval, 0.77 to 1.01; P=0.06). There were 6 percent fewer hospitalizations overall in that group than in the placebo group, and fewer patients were hospitalized for worsening heart failure (26.8 percent vs. 34.7 percent; risk ratio, 0.72; 95 percent confidence interval, 0.66 to 0.79; P<0.001). In the ancillary trial, the findings regarding the primary combined outcome of death or hospitalization due to worsening heart failure were consistent with the results of the main trial. Digoxin did not reduce overall mortality, but it reduced the rate of hospitalization both overall and for worsening heart failure. These findings define more precisely the role of digoxin in the management of chronic heart failure.
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              Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group.

              Milrinone, a phosphodiesterase inhibitor, enhances cardiac contractility by increasing intracellular levels of cyclic AMP, but the long-term effect of this type of positive inotropic agent on the survival of patients with chronic heart failure has not been determined. We randomly assigned 1,088 patients with severe chronic heart failure (New York Heart Association class III or IV) and advanced left ventricular dysfunction to double-blind treatment with (40 mg of oral milrinone daily (561 patients) or placebo (527 patients). In addition, all patients received conventional therapy with digoxin, diuretics, and a converting-enzyme inhibitor throughout the trial. The median period of follow-up was 6.1 months (range, 1 day to 20 months). As compared with placebo, milrinone therapy was associated with a 28 percent increase in mortality from all causes (95 percent confidence interval, 1 to 61 percent; P = 0.038) and a 34 percent increase in cardiovascular mortality (95 percent confidence interval, 6 to 69 percent; P = 0.016). The adverse effect of milrinone was greatest in patients with the most severe symptoms (New York Heart Association class IV), who had a 53 percent increase in mortality (95 percent confidence interval, 13 to 107 percent; P = 0.006). Milrinone did not have a beneficial effect on the survival of any subgroup. Patients treated with milrinone had more hospitalizations (44 vs. 39 percent, P = 0.041), were withdrawn from double-blind therapy more frequently (12.7 vs. 8.7 percent, P = 0.041), and had serious adverse cardiovascular reactions, including hypotension (P = 0.006) and syncope (P = 0.002), more often than the patients given placebo. Our findings indicate that despite its beneficial hemodynamic actions, long-term therapy with oral milrinone increases the morbidity and mortality of patients with severe chronic heart failure. The mechanism by which the drug exerts its deleterious effects is unknown.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                November 2019
                22 November 2019
                : 98
                : 47
                : e18144
                Affiliations
                [a ]Department of Intensive Care Unit
                [b ]Department of Ultrasound, Hebei General Hospital, Hebei, China.
                Author notes
                []Correspondence: He-ling Zhao, No. 348 Heping West Road, Xinhua Area, Shijiazhuang, Hebei Province, China (e-mail: epson777777@ 123456163.com ).
                Article
                MD-D-18-09371 18144
                10.1097/MD.0000000000018144
                6882628
                31764856
                3ea4686a-250f-43fc-95ff-414b11a9c25d
                Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0

                History
                : 12 December 2018
                : 12 October 2019
                : 30 October 2019
                Categories
                3400
                Research Article
                Systematic Review and Meta-Analysis
                Custom metadata
                TRUE

                heart failure,hemodynamic,inotropic agent,network meta-analysis

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