) is a calcium
sensitiser used in the management of acutely decompensated congestive heart failure
. It is marketed under the trade name Simdax
Mode of action
Levosimendan is a calcium sensitiser – it increases the sensitivity of the heart to calcium, thus increasing cardiac contractility without a rise in intracellular calcium. Levosimendan exerts its positive inotropic
effect by increasing calcium sensitivity of myocytes
by binding to cardiac troponin C
in a calcium-dependent manner. It also has a vasodilatory
effect, by opening adenosine triphosphate
channels in vascular smooth muscle
to cause smooth muscle relaxation. The combined inotropic and vasodilatory actions result in an increased force of contraction, decreased preload
and decreased afterload
. Moreover, by opening also the mitochondrial (ATP)-sensitive potassium channels in cardiomyocytes, the drug exerts a cardioprotective effect.
Levosimendan is indicated for inotropic support in acutely-decompensated
severe congestive heart failure
Some of the Phase-III studies in the extensive clinical program were the trials LIDO (200 patients), RUSSLAN (500), CASINO (250), REVIVE-I (100), REVIVE-II (600) and finally SURVIVE (1350), a head-to-head trial between levosimendan and dobutamine in acute decompensated heart failure. In total, the clinical data base includes more than 3500 patients in Phase IIb and III double-blind studies, which is the highest number ever in testing a drug for acute decompensated heart failure.
Despite an initial reduction in plasma B-type natriuretic peptide level in patients in the levosimendan group compared with patients in the dobutamine group in a head to head comparison study, levosimendan did not significantly reduce all-cause mortality at 180 days or affect any secondary clinical outcomes.
The drug has a marketing authorization in 48 countries.
The use of levosimendan is contraindicated in patients with: moderate-to-severe renal impairment
, severe hepatic
impairment, severe ventricular
filling or outflow obstruction, severe hypotension
, and/or history of torsades de pointes
Common adverse drug reactions
(≥1% of patients) associated with levosimendan therapy include: headache, hypotension, arrhythmias
, atrial tachycardia
, ventricular tachycardia
), myocardial ischaemia
and/or nausea (Rossi, 2006).
Levosimendan is marketed as a 2.5 mg/mL concentrated solution for IV infusion. The concentrate is diluted with glucose
5% solution before infusion.