Efeito do levosimendan em pacientes com insuficiência cardíaca sistólica severa e agravamento da função renal

Zorlu, Ali; Yücel, Hasan; Yontar, Osman Can; Karahan, Oğuz; Tandoğan, İzzet; Katrancioglu, Nurkay; Yilmaz, Mehmet Birhan

doi:10.1590/s0066-782x2012005000048

Cited by 20 publications

(7 citation statements)

References 25 publications

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“…Zorlu et al [ 30 ] studied the effect of levosimendan in patients with severe systolic heart failure and worsening renal function and subclassified the patients into those without and with worsening renal function, defined as an increase in serum creatinine >0.3 mg/dL. Levosimendan significantly improved renal function (creatinine, GFR) in those with worsening renal function but not in those with stable renal function.…”

Section: Clinical Evidencementioning

confidence: 99%

Renal Effects of Levosimendan: A Consensus Report

Yilmaz

Grossini

Silva-Cardoso

et al. 2013

Cardiovasc Drugs Ther

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Renal dysfunction is common in clinical settings in which cardiac function is compromised such as heart failure, cardiac surgery or sepsis, and is associated with high morbidity and mortality. Levosimendan is a calcium sensitizer and potassium channel opener used in the treatment of acute heart failure. This review describes the effects of the inodilator levosimendan on renal function. A panel of 25 scientists and clinicians from 15 European countries (Austria, Finland, France, Hungary, Germany, Greece, Italy, Portugal, the Netherlands, Slovenia, Spain, Sweden, Turkey, the United Kingdom, and Ukraine) convened and reached a consensus on the current interpretation of the renal effects of levosimendan described both in non-clinical research and in clinical study reports. Most reports on the effect of levosimendan indicate an improvement of renal function in heart failure, sepsis and cardiac surgery settings. However, caution should be applied as study designs differed from randomized, controlled studies to uncontrolled ones. Importantly, in the largest HF study (REVIVE I and II) no significant changes in the renal function were detected. As it regards the mechanism of action, the opening of mitochondrial KATP channels by levosimendan is involved through a preconditioning effect. There is a strong rationale for randomized controlled trials seeking beneficial renal effects of levosimendan. As an example, a study is shortly to commence to assess the role of levosimendan for the prevention of acute organ dysfunction in sepsis (LeoPARDS).

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Section: Clinical Evidencementioning

confidence: 99%

Renal Effects of Levosimendan: A Consensus Report

Yilmaz

Grossini

Silva-Cardoso

et al. 2013

Cardiovasc Drugs Ther

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“…The Longitudinal Investigation of Depression Outcomes study indicated that compared with dobutamine, levosimendan significantly reduced the serum creatinine level and mortality in patients with HF [18]. To date, several clinical trials have examined the effects of inotropic agents on mortality and renal protection in patients with acute and chronic HF [19][20][21][22]. However, these promising agents have exhibited mixed outcomes in some clinical trials [21,23].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Comparison of the Effect of Inotropes on Cardiorenal Syndrome in Patients with Advanced Heart Failure: A Network Meta-Analysis of Randomized Controlled Trials

Chen

Lin

Chen

et al. 2021

JCM

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Prevention of cardiorenal syndrome through treatment with inotropic agents remains challenging. This network meta-analysis evaluated the safety and renoprotective effects of inotropes on patients with advanced heart failure (HF) using a frequentist random-effects model. A systematic database search was performed until 31 January 2021, and a total of 37 trials were included. Inconsistency, publication bias, and subgroup analyses were conducted. The levosimendan group exhibited significantly decreased mortality compared with the control (odds ratio (OR): 0.62; 95% confidence interval (CI): 0.46–0.84), milrinone (OR: 0.50; 95% CI: 0.30–0.84), and dobutamine (OR: 0.75; 95% CI: 0.57–0.97) groups. In terms of renal protection, levosimendan (standardized mean difference (SMD): 1.67; 95% CI: 1.17–2.18) and dobutamine (SMD: 1.49; 95% CI: 0.87–2.12) more favorably improved the glomerular filtration rate (GFR) than the control treatment did, but they did not significantly reduce the incidence of acute kidney injury. Furthermore, levosimendan had the highest P-score, indicating that it most effectively reduced mortality and improved renal function (e.g., GFR and serum creatinine level), even in patients with renal insufficiency. In conclusion, levosimendan is a safe alternative for protecting renal function on cardiorenal syndrome in patients with advanced HF.

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“…The LIDO (Levosimendan Infusion versus Dobutamine) Study, which examined inotropic treatment among those with low‐output HF, showed that levosimendan brought about a significant decrease in serum creatinine compared with dobutamine 10. Subsequent studies have suggested that levosimendan has a beneficial effect on renal function among people with acute and chronic HF 11, 12, 13. Bragadottir et al found that levosimendan, when compared with placebo, increased both renal blood flow (RBF) and glomerular filtration rate (GFR) in post–cardiac surgery patients with normal preoperative serum creatinine 14.…”

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confidence: 99%

Differential Effects of Levosimendan and Dobutamine on Glomerular Filtration Rate in Patients With Heart Failure and Renal Impairment:A Randomized Double‐Blind Controlled Trial

Lannemyr

Ricksten

Rundqvist

et al. 2018

JAHA

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BackgroundThe management of the cardiorenal syndrome in advanced heart failure is challenging, and the role of inotropic drugs has not been fully defined. Our aim was to compare the renal effects of levosimendan versus dobutamine in patients with heart failure and renal impairment.Methods and ResultsIn a randomized double‐blind study, we assigned patients with chronic heart failure (left ventricular ejection fraction <40%) and impaired renal function (glomerular filtration rate <80 mL/min per 1.73 m2) to receive either levosimendan (loading dose 12 μg/kg+0.1 μg/kg per minute) or dobutamine (7.5 μg/kg per minute) for 75 minutes. A pulmonary artery catheter was used for measurements of systemic hemodynamics, and a renal vein catheter was used to measure renal plasma flow by the infusion clearance technique for PAH (para‐aminohippurate) corrected by renal extraction of PAH. Filtration fraction was measured by renal extraction of chromium ethylenediamine tetraacetic acid. A total of 32 patients completed the study. Following treatment, the levosimendan and dobutamine groups displayed similar increases in renal blood flow (22% and 26%, respectively) with no significant differences between groups. Glomerular filtration rate increased by 22% in the levosimendan group but remained unchanged in the dobutamine group (P=0.012). Filtration fraction was not affected by levosimendan but decreased by 17% with dobutamine (P=0.045).ConclusionsIn patients with chronic heart failure and renal impairment, levosimendan increases glomerular filtration rate to a greater extent than dobutamine and thus may be the preferred inotropic agent for treating patients with the cardiorenal syndrome.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT02133105.

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Efeito do levosimendan em pacientes com insuficiência cardíaca sistólica severa e agravamento da função renal

Cited by 20 publications

References 25 publications

Renal Effects of Levosimendan: A Consensus Report

Renal Effects of Levosimendan: A Consensus Report

Comprehensive Comparison of the Effect of Inotropes on Cardiorenal Syndrome in Patients with Advanced Heart Failure: A Network Meta-Analysis of Randomized Controlled Trials

Differential Effects of Levosimendan and Dobutamine on Glomerular Filtration Rate in Patients With Heart Failure and Renal Impairment:A Randomized Double‐Blind Controlled Trial

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