Haemodynamic interactions of a new calcium sensitizing drug levosimendan and captopril.
OBJECTIVE
Levosimendan in a new inodilator drug that sensitizes troponin C in heart muscle cells to calcium, thus improving contractility. In previous studies, a single 2 mg intravenous dose of levosimendan increased cardiac output (CO) in healthy volunteers by about 40% and decreased pulmonary capillary wedge pressure in heart failure patients by 40-50%. The aim of the present, double-blind study was to evaluate the safety of concomitant use of levosimendan and an ACE-inhibiting drug.


METHODS
The haemodynamic effects of levosimendan, given with or without captopril, were evaluated by using 2-dimensional echocardiography, repeated blood pressure measurements and by ambulatory ECG recordings. Twenty-four male patients with stable NYHA II-III heart failure (EF < 40%) after a previous myocardial infarct were given, in randomised order, a single i.v. infusion of levosimendan or placebo. The infusions were repeated after 2 weeks treatment with upto 50 mg b.i.d. of captopril. Twelve patients received levosimendan 1 mg and twelve received 2 mg.


RESULTS
Mean CO was increased from 6.0 to 6.8 1 . min-1 in patients receiving 1 mg levosimendan compared to placebo, but only from 6.3 to 6.5 1 . min-1 in patients receiving 2 mg. The increase in CO was statistically significant when all levosimendan patients were compared to placebo. Heart rate did not change after either dose. Mean stroke volume increased significantly after 1 mg but not after 2 mg of levosimendan. The addition of captopril did not change the effects of levosimendan. No additional decrease in systolic or diastolic blood pressure was observed when levosimendan and captopril were given concomitantly.


CONCLUSIONS
It seems that concomitant treatment with captopril does not change the haemodynamic effects of levosimendan. No adverse haemodynamic interactions were seen.
Antila
S
S
Orion-Farmos, Espoo, Finland.
Eha
J
J
Heinpalu
M
M
Lehtonen
L
L
Loogna
I
I
Mesikepp
A
A
Planken
U
U
Sandell
E P
EP
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D004452:Echocardiography / Q000187:drug effects; D015716:Electrocardiography, Ambulatory / Q000187:drug effects; D006207:Half-Life; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006835:Hydrazones / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D011724:Pyridazines / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000077464:Simendan
D000806:Angiotensin-Converting Enzyme Inhibitors; D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan; D002216:Captopril