The Pharmaceutical Journal
Vol 269 No 7209 p151
3 August 2002

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The Lancet (www.thelancet.com)

Calcium sensitiser lowers mortality

A novel calcium sensitiser, levosimendan (Simdax), lowers mortality and improves cardiac function in patients with low output heart failure, a new study shows.

Levosimendan, manufactured by Orion Pharma and being developed for the treatment of acutely decompensated heart failure, has a dual mechanism of action. It binds to and sensitises troponin C, a protein that affects heart muscle contraction, increasing the contractile force on the heart and avoiding the build-up of excessive calcium which can cause arrhythmia. It also leads to vasodilation through the opening of ATP-sensitive potassium channels in vascular smooth muscle. The authors of the study say that by exerting these inotropic and vasodilatory actions, levosimendan increases cardiac output without increasing myocardial oxygen demand.

Professor Ferenc Follath, University Hospital Zürich, Switzerland, and colleagues compared the effects of levosimendan with dobutamine on haemodynamic performance in 203 patients with severe low output heart failure after a 24-hour infusion period. Eleven countries, including the United Kingdom, were involved in the randomised, double-blind trial.

They say that levosimendan improved haemodynamic performance more effectively than dobutamine. After 24 hours, haemodynamic improvement was achieved in 28 per cent of patients treated with levosimendan (n=103) compared with 15 per cent of those treated with dobutamine (n=100). Eight patients in the levosimendan group died within 31 days compared with 17 patients in the dobutamine group and after 180 days there had been 27 deaths and 38 deaths, respectively.

The researchers say that the haemo-dynamic effects of levosimendan, unlike those of dobutamine, were not attenuated by the concomitant use of beta-blockers. "This finding is important in view of the increasing evidence for and the usefulness of beta-blockers for the management of severe heart failure," they say. The study provided no information on the duration of infusion of levosimendan needed for optimum benefit or on how often it may be repeated in patients who do not respond initially or who relapse after an initial response.

However, they conclude: "Our results are encouraging and suggest that levosimendan could be, for several reasons, a better choice than dobutamine as inotropic therapy for patients with decompensated heart failure." (Lancet 2002;360:196)