Dataset Information

Levosimendan Efficacy and Safety: 20 Years of SIMDAX in Clinical Use.

ABSTRACT: Levosimendan was first approved for clinical use in 2000, when authorization was granted by Swedish regulatory authorities for the hemodynamic stabilization of patients with acutely decompensated chronic heart failure (HF). In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitization and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced HF, right ventricular failure, pulmonary hypertension, cardiac surgery, critical care, and emergency medicine. Levosimendan is currently in active clinical evaluation in the United States. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and noncardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, the United Kingdom, and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute HF arena in recent times and charts a possible development trajectory for the next 20 years.

SUBMITTER: Papp Z

PROVIDER: S-EPMC7340234 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Levosimendan Efficacy and Safety: 20 Years of SIMDAX in Clinical Use.

Papp Zoltán Z Agostoni Piergiuseppe P Alvarez Julian J Bettex Dominique D Bouchez Stefan S Brito Dulce D Černý Vladimir V Comin-Colet Josep J Crespo-Leiro Marisa G MG Delgado Juan F JF Édes István I Eremenko Alexander A AA Farmakis Dimitrios D Fedele Francesco F Fonseca Cândida C Fruhwald Sonja S Girardis Massimo M Guarracino Fabio F Harjola Veli-Pekka VP Heringlake Matthias M Herpain Antoine A Heunks Leo M A LMA Husebye Tryggve T Ivancan Višnja V Karason Kristjan K Kaul Sundeep S Kivikko Matti M Kubica Janek J Masip Josep J Matskeplishvili Simon S Mebazaa Alexandre A Nieminen Markku S MS Oliva Fabrizio F Papp Julius G JG Parissis John J Parkhomenko Alexander A Põder Pentti P Pölzl Gerhard G Reinecke Alexander A Ricksten Sven-Erik SE Riha Hynek H Rudiger Alain A Sarapohja Toni T Schwinger Robert H G RHG Toller Wolfgang W Tritapepe Luigi L Tschöpe Carsten C Wikström Gerhard G Lewinski Dirk von DV Vrtovec Bojan B Pollesello Piero P

Journal of cardiovascular pharmacology 20200701 1

Levosimendan was first approved for clinical use in 2000, when authorization was granted by Swedish regulatory authorities for the hemodynamic stabilization of patients with acutely decompensated chronic heart failure (HF). In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitization and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved i ...[more]

PMID: 32639325

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Project description:AimsThe aim of the LAICA study was to evaluate the long-term effectiveness and safety of intermittent levosimendan infusion in patients with advanced heart failure (AdHF).Methods and resultsThis was a multicentre, randomized, double-blind, placebo-controlled clinical trial of intermittent levosimendan 0.1 μg/kg/min as a continuous 24-h intravenous infusion administered once monthly for 1 year in patients with AdHF. The primary endpoint [incidence of rehospitalization (admission to the emergency department or hospital ward for >12 h) for acute decompensated HF or clinical deterioration of the underlying HF] occurred in 23/70 (33%) of the levosimendan group (Group I) and 12/27 (44%) of the placebo group (Group II) (P = 0.286). The incidence of hospital readmissions for acute decompensated HF (Group I vs. Group II) at 1, 3, 6, and 12 months was 4.2% vs. 18.2% (P = 0.036); 12.8% vs. 33.3% (P = 0.02); 25.7% vs. 40.7% (P = 0.147); 32.8% vs. 44.4% (P = 0.28), respectively. In a secondary pre-specified time-to-event analysis no differences were observed in admission for acute decompensated HF between patients treated with levosimendan compared with placebo (hazard ratio 0.66; 95% CI, 0.32-1.32; P = 0.24). Cumulative incidence for the aggregated endpoint of acute decompensation of HF and/or death at 1 and 3 months were significatively lower in the levosimendan group than in placebo group [5.7% vs. 25.9% (P = 0.004) and 17.1% vs. 48.1% (P = 0.001), respectively], but not at 6 and 12 months [34.2% vs. 59.2% (P = 0.025); 41.4% vs. 66.6% (P = 0.022), respectively]. Survival probability was significantly higher in patients who received levosimendan compared with those who received placebo (log rank: 4.06; P = 0.044). There were no clinically relevant differences in tolerability between levosimendan and placebo and no new safety signals were observed.ConclusionsIn our study, intermittent levosimendan in patients with AdHF produced a statistically non-significant reduction in the incidence of hospital readmissions for acute decompensated HF, a significantly lower cumulative incidence of acute decompensation of HF and/or death at 1 and 3 month of treatment and a significant improvement in survival during 12 months of treatment.

Project description:BackgroundCanada was one of the first countries to regulate the medical use of cannabis. However, literature on Canada's medical cannabis program is limited.MethodsWe use administrative data from the medical cannabis program, and licensed cannabis vendor catalog data to describe a) the participation of patients, physicians, and cannabis vendors in the program from its inception in 1999 to 2021, and b) trends in medical cannabis consumption, prices and potency. We also use national surveys conducted over the last several decades to estimate trends in regular cannabis use (medical or otherwise) and how it changed during the medical cannabis access regimes.ResultsIn 2001, the Canadian government granted access to those with physician-documented evidence of a severe health problem that could not be managed using conventional therapies. Most patients accessed cannabis grown under a personal production license. By 2013, authorized daily cannabis dosages were very high. In 2014, the government, concerned over illegal diversion, required that cannabis be purchased from a licensed commercial grower; personal production was banned. Physicians were given responsibility for authorizing patient access. To fill the regulatory void, the physician regulatory bodies in Canada imposed their own prescribing restrictions. After these changes, the number of physicians who were willing to support patient cannabis use markedly decline but the number of patients participating in the program sharply increased. Medical cannabis use varied by province-rates were generally lower in provinces with stricter regulations on physician cannabis prescribing. Most varieties of cannabis oil available for sale are now high in CBD and low in THC. Dry cannabis varieties, conversely, tend to be high in THC and low in CBD. Inflation adjusted prices of most varieties of medical cannabis have declined over time. We find that rates of daily cannabis use (medical or otherwise) increased markedly after the 2014 policy regime. The fraction of Canadians using cannabis daily increased again after the 2018 legalization of recreational cannabis; at the same time, participation in the medical access program declined.ConclusionThe implications for patient health outcomes of changes in the medical cannabis program and legalization of recreational use remains an important area for future research.

Dataset Information

Levosimendan Efficacy and Safety: 20 Years of SIMDAX in Clinical Use.

Publications

Levosimendan Efficacy and Safety: 20 Years of SIMDAX in Clinical Use.

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