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Binu George , Heather Bury Critical care Journal Club May 2014

Effect of Levosimendan on the Short-Term Clinical Course of Patients With Acutely Decompensated Heart Failure. Binu George , Heather Bury Critical care Journal Club May 2014. Background. Over a million people hospitalised in the US for treatment of ADHF

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Binu George , Heather Bury Critical care Journal Club May 2014

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  1. Effect of Levosimendan on theShort-Term Clinical Course of Patients With Acutely Decompensated Heart Failure Binu George , Heather Bury Critical care Journal Club May 2014

  2. Background • Over a million people hospitalised in the US for treatment of ADHF • Usually receive IV diuretics , peripheral vasdilators ,positive inotropes • Unclear how haemodynamics translate to clinical benefits • Average hospital stay 5 days

  3. Methods • REVIVE 1 and 2 carried out in 103 centres in the US, Australia and Israel between December 2001 and December 2004 • All patients with ADHF who remained dyspneic inspite of treatmet with intravenous diuretics

  4. Study Plan • Randomly assigned (double blind) to treatments with placebo or levosimendan which was added to their existing treatment plan • Study endpoints- composite of clinically relevant measures

  5. Outcome measurement • Primary end point in both trials -clinical course during first 5 days characterized as improved , unchanged or worse. • Secondary endpoint- BNP at 24 hrs ,changes in global assessment at 6hrs ,changes in perception of dyspnoea at 6hrs ,numer of days alive (1-14 days after randomization),NHYA functional status at day 5,all cause mortality during first 90 days

  6. Worsening clinical status requiring rescue therapy in revive 1 and 2

  7. Results • 12% of levosimendan group and 7% of placebo group discontinued before 24 hrs • Primary endpoints- patients improved on levosimendan compared to placebo • In both groups no differences in groupsin number of days alive over 14 days

  8. Results • Levosimendan arm briefer hospital stays-46%vs37% • NYHA functional status was not significantly different between both groups • Safety- higher number of adverse effects with levosimendan

  9. discussion • Robust study , demonstrates favourable effect on short term clinical course of patients with ADHF • Likely reason for incresed mortality in levosimendan arm due to increased used of loading dose and approach which is no longer followed

  10. Levosimendan • Mode of Action • Calcium sensitisation • Increased cardiac contractility • K+ ATP channel opening • Pharmacokinetics • Onset of action: 1 minute • Half life 1 hour • Excreted in faeces and urine • Prolonged haemodynamic effects

  11. Levosimendan effects…. • Cardioprotective effect • Anti inflammatory effect • Neurohormonal effect • Improves coronary circulation • Antistunning effect • Haemodynamic effects

  12. LIDO Study • Multicenter ,double blind,double dummy.randomized study • Designed to compare clinical and haematological effects of levosimendan vs Dobutamine in low output heart failure • 203 patients- levosimendan improved haemodynamic performance and decreased mortality for upto 180 days

  13. RUSSLAN TRIAL • Double blind placebo controlled • Evaluating different doses of levosimendan vs placebo in patients with heart failure secondary to MI • 504 patients – higher dose , greater side effects • Overall mortality better than placebo group (at 14 days)

  14. CASINO TRIAL • Randomised , double blinded, double dummy and parallel group study • 299 patients NYHA 4 (LVEF less than 35%) • Stopped prematurely – significant survival benefit with levosimendan compared with dobutamine

  15. SURVIVE TRIAL • Randomized ,double blind, double dummy, prospective controlled study • 1327 patients (LVEF-less than 35%)- not responding to IV diureticsand vasodilator therapy • Primary endpoint- all cause mortality in 180 days – no statistical difference • 25% lower mortality compared to dobutamine 6 hrs,24 hrs , 5,14,30 days

  16. Levosimendan Facts !! • Well tolerated • Side effects – headache ,hypotension,dizzyness,nausea • Can cause VT ,AF at higher doses • Recommended dose 6-24 μg/kg/min administerted in 10-20 min and maintainance dose- 0.05-0.2 μg/kg/min over 24 hrs

  17. Facts !! • Not licensed for use in the UK and USA however still used • Not recommended for use in patients with Bp less than 90 systolic • Can be used in conjunction with betablockers, noradrenaline • Can also be used in septic shock (some proven benefit)

  18. Discussion • New inodilator agent for therapy in end stage heart failure • Proven benefits compared to dobutamine • Further trials may help clarify its effects on mortality and use in clinical practice

  19. Any Questions ???

  20. Thank You !!

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