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SIMDAX in Acute Heart Failure

 

SIMDAX RELIEVES SYMPTOMS IN AHF

SIMDAX improves symptoms of dyspnoea and fatigue in acute heart failure. In the Phase III regulatory study REVIVE, symptoms over the 5-day assessment period improved significantly more with SIMDAX than with placebo when administered on top of the standard of care.1

Improvement of clinical status Improvement in dyspnea

Reference: 1. Packer M. et al. JCHF. 2013;1(2): 103-11.

 

…WITH SUSTAINED HEMODYNAMIC AND NEUROHORMONAL EFFECTS

The hemodynamic effects of SIMDAX on cardiac output (CO) and pulmonary capillary wedge pressure (PCWP) have been shown in several clinical trials.1-3 The effect of SIMDAX is sustained,1,4 as also seen in a prolonged decrease of brain natriuretic peptide in the SURVIVE clinical trial.4

Sustained hemodynamic effects Sustained effects of neurohormone levels

 

References: 1. Lilleberg J et al. Eur Heart J. 1998;19:660–668. 2. Follath F. et al. Lancet. 2002;360:9328):196-202. 196-202. 3. Kivikko M et al. Circulation. 2003 Jan 7;107(1):81-6. 4. Mebazaa A. et al. JAMA. 2007;297(17):1883-91.

 

…THE BENEFITS ARE PRONOUNCED IN THE
PRESENCE OF β-BLOCKERS

In the ESC heart failure guidelines1 SIMDAX is recommended for acute heart failure in patients with reduction of cardiac output and in presence of β-blockers.1 SIMDAX can be used in patients receiving beta-blocking agents without loss of efficacy.2 Indeed a beneficial effect on 31 days survival is also noticeable in presence of β-blockers.3

Effects of previous text

Hazard ratios

References: 1. Ponikowski P et al. Eur Heart J 2016;37:2129-2200. 2. Follath F. et al. Lancet. 2002;360:9328):196-202. 196-202. 3. Mebazaa A et al Eur J Heart Fail. 2009;11(3):304-11.

 

HOW TO USE SIMDAX IN AHF

Example of use

AHF patients with systolic dysfunction (LVEF < 40%) and with the following characteristics may be considered for SIMDAX treatment:
• signs of hypoperfusion, i.e. cool extremities, oliguria
• severe pulmonary oedema
• inadequate response to traditional treatment (however, the start of the SIMDAX infusion should not be unnecessarily delayed.)

Exclusion criteria

• severe hypotension and/or tachycardia
• severe renal impairment
• severe hepatic impairment
• history of Torsades de Pointes

Dosing

Dosing of SIMDAX will be according to the SPC. However, the bolus dose should only be given if immediate effects are needed and the baseline blood pressure is > 120 mmHg.1 Thus, in most cases:
• SIMDAX-infusion will be started with an infusion rate of 0.1 mcg/kg/min.
• The rate can be increased to 0.2 mcg/kg/min if further effect is warranted or decreased to 0.05 mcg/kg/min if adverse effects (e.g. hypotension) occurs.
• The maximum duration of the infusion should not exceed 24 hours.

What to expect?  Other clinical effects

Reference: 1. Nieminen MS et al. Heart Lung Vessels.

 

IN AHF THE EFFECTS OF SIMDAX ALLOW A SHORTER HOSPITAL STAY

SIMDAX, on top of standard of care, shortens hospital stay in acute heart failure. These data have been shown in a phase III study (vs placebo).1,2

Hospital stay is reduced

References: 1. De Lissovoy G et al. Eur J Health Econ. 2010;11:185–193. 2. Packer M et al. JACC Heart Fail. 2013;1(2):103-11.

 

WHICH IS CONFIRMED BY META-ANALYSIS OF SEVERAL STUDIES

These results are corroborated by a meta-analysis of 8 studies in which SIMDAX was used in cardiology settings: Length of stay in hospital was decreased by 1.59 days in SIMDAX treated patients in addition to a significant reduction in mortality.1

 Meta-analysis of the levosimendan effects on length of stay in hospital1

 

 

 

 

 

 

 

 

 

 Reference: 1. Landoni G et al. Crit Care Med. 2012;40:634–646 (electronic supplementary material).

 

BETTER OUTCOME THAN WITH OTHER VASOACTIVE I.V. AGENTS

 ALARM-HF1 registry

The effect of i.v. vasoactive drugs on in-hospital mortality was studied in 4.953 AHF patients (Figure 1. unadjusted analysis). A propensity-based analysis was performed to compare in-hospital mortality of patients treated only with SIMDAX® versus those treated with only catecholamines showing a significant reduction in the risk of in-hospital mortality (HR 0.25, 95% CI 0.07–0.85).

Figure 1

Reference: 1. Mebazaa A et al. Intensive Care Med. 2011;37:290-301.

 

...WITH NO COMPROMISE ON LONG-TERM SURVIVAL

The use of SIMDAX was associated with improved survival. A meta-analysis of 23 studies describing the use of SIMDAX in cardiology settings showed a 25% risk reduction [SIMDAX 441/2207 (20.0%), control 484/1893(25.6%), RR=0.75 (95% CI 0.63, 0.91), p for effect: 0.003, p for heterogeneity: 0.131, NNT=18].1

 Meta-analysis on mortality of levosimendan clinical trials in cardiology settings1

Reference: 1. Landoni G et al. Crit Care Med. 2012;40:634–646.

 

IMPROVEMENT OF HEMODYNAMIC PARAMETERS IN CARDIOGENIC SHOCK

SIMDAX increases cardiac index in patients who did not improve with conventional therapy (including use of dobutamine and
norepinephrine).1'

 Levosimendan has effects on both left and right ventricular performance

Reference: 1. Russ MA et al. Crit Care Med. 2009;37:3017-23.

 

...WITH NO COMPROMISE ON OUTCOME

SIMDAX was compared with enoximone in 30 day survival in patients with cardiogenic shock 32 patients with refractory cardiogenic shock complicating acute myocardial infarction.1 The standard of care consisted of immediate revascularisation by percutaneous coronary intervention, IABP, fluid resuscitation and conventional inotropes.

SIMDAX use was associated with similar hemodynamic effects, but mortality was significantly lower.

30 day survival in patients with cardiogenic shock

Reference: 1. Fuhrmann JT et al. Crit Care Med. 2008 ;36:2257-66.

 

IMPROVEMENT OF LEFT VENTRICULAR FUNCTION IN HEART FAILURE AFTER ACUTE CORONARY SYNDROME

Sixty patients developing clinical signs of heart failure or cardiogenic shock within 48 hours after a primary percutaneous coronary intervention were randomized to a 25 hour infusion of SIMDAX or placebo.1 SIMDAX significantly improved the change in wall motion score index from baseline to day 5
as measured by echocardiography (see chart).1 One and four patients died in the SIMDAX and placebo groups, respectively.1

Levosimendan effect on wall motion score index in acute heart failure following acute coronary syndrome

Reference: 1. Husebye T et al. Eur J Heart Fail. 2013;15:565–572.

 

...WITH NO COMPROMISE ON SURVIVAL

In the placebo-controlled RUSSLAN trial, 6-hour infusions of SIMDAX were shown to be safe in patients who developed heart failure after an acute myocardial infarction, and significantly increased survival at 14 days after administration.1 The positive effect of SIMDAX® on survival in these settings was confirmed by a recent meta-analysis of nine studies.2

The effect of levosimendan on survival in acute heart failure following acute myocardial infarction

References: 1. Moiseyev V et al. Eur Heart J. 2002;23:1422–1432. 2. Shang G et al. Am J Cardiovasc Drugs 2017 [ePub Jun 8] DOI 10.1007/s40256-017-0237-0.

 

RECOMMENDATION ON THE USE IN ACS RELATED AHF

Expert panel consensus on the use of vasoactive drugs in acute heart failure related to acute coronary syndrome1,a

Reference: 1. Nieminen MS et al. Int J Cardiol. 2016;218:150–157.

 

DOSING AND MONITORING IN ACS RELATED AHF

SIMDAX dosing:1

  • The recommended infusion ratesare 0.05–0.1 μg/kg/min for 24 hours
  • Bolus dose should be avoided due to the risk of hypotension. If a faster onset of action is needed, an infusion of 0.2 μg/kg/min could be used during the first 60 min

Monitoring of treatment:1

  • Hypotension, a potential side effect of SIMDAX, is of particular concern in patients with ACS
  • Continuous hemodynamic monitoring is recommended.This includes ECG, blood pressure, SaO2, heart rate, urinary output, potassium levels, and clinical signs. End-organ function (liver, kidney, mental status) should be evaluated

Reference: 1. SIMDAX SPC.

 

EASING THE CHALLENGE OF TREATING THE FAILING HEART1 WITH LONG LASTING HEMODYNAMIC STABILIZATION

SIMDAX GIVES YOU TIME BY PROVIDING:

  • Hemodynamic improvement2,3
  • Symptomatic improvement2,3
  • Sustained effects2
  • Synergies with β-blockers4
  • Shorter hospital stay5,6
  • Reduced re-hospitalization7

References: 1. Pölzl G et al. Int J Cardiol 2017 [ePub May 24]. 2. Nieminen MS et al. Int J Cardiol. 2014;174(2):360–367. 3. Husebye T et al. Eur J Heart Fail. 2013;15:565–572. 4. Follath F et al. Lancet. 2002;360:196–202. 5. De Lissovoy G et al. Eur J Health Econ. 2010;11:185–193. 6. Landoni G et al. Crit Care Med. 2012;40:634–646. 7. Silvetti S et al. ESC Heart Failure 2017;4:595-604.