Although acutely decompensated heart failure is a very common cause of hospitalization, most treatments commonly used have not been validated in large randomized clinical trials.
Inotropic agents currently used for acute heart failure, including Dobutamine, Milrinone, and Nesiritide, have been associated with an increased risk of mortality.

Levosimendan ( Simdax ) is a new agent that induces calcium sensitization for positive inotropic effect and activates vascular smooth-muscle ATP-dependent potassium channels for vasodilatation. The resulting improvement of cardiac function and blood flow may provide a hemodynamic support in patients with acutely decompensated heart failure.

The SURVIVE trial was designed to test the effect of Levosimendan against Dobutamine on death and major clinical events among patients hospitalized for acutely decompensated heart failure.

SURVIVE-W was a double-blind, active control, double dummy, randomized clinical trial.
Patients were eligible for inclusion if they had acutely decompensated heart failure, left ventricular ejection fraction <30%, and a clinical need for intravenous inotropic support, as evidenced by an insufficient response to intravenous diuretics and/or vasodilators and at least one of the following:

1) oliguria ( mean urine output <30 mL/h for at least 6 h ) not due to hypovolemia,
2) persistent dyspnea at rest,
3) mechanical ventilation for heart failure, or
4) invasive hemodynamic demonstration of a pulmonary wedge pressure ( 18 mm Hg and/or cardiac index =2.2 L/(min · m2 ).

A total of 1327 patients were randomized to receive either Dobutamine [ minimum dose 5 µg/( kg · min ) for at least 2 h ] or Levosimendan [12-µg/kg bolus followed by 0.2 µg/( kg · min ) ].

The primary end point was all cause mortality within 180 days.

The incidence of the primary end point was 26% in the Levosimendan group and 28% in the Dobutamine group ( hazard ratio [HR] 0.91 ).
No differences were observed in the incidence of the secondary end point, all-cause mortality within 31 days ( 12% vs 14% for Levosimendan and Dobutamine, respectively, HR 0.85 ).

A post hoc analysis evaluating all-cause mortality within 5 days showed a trend in favor of Levosimendan ( 4% vs 6%, HR 0.72 ).
The trend was stronger among patients with a history of heart failure ( HR 0.58 ).
No differences were observed in the incidence of hypotension, ventricular tachycardia, and serum creatinine changes.
Atrial fibrillation was more common in the Levosimendan group while cardiac failure was more common in the Dobutamine group.
A more marked and persistent decrease in the levels of brain-type natriuretic peptide was observed in the Levosimendan group compared with the Dobutamine group.

The SURVIVE trial failed to demonstrate benefits of Levosimendan compared with Dobutamine.
In fact, no differences were observed in the occurrence of both the primary and secondary end points.
The possible clinical implications of the decrease in the level of brain-type natriuretic peptide are not clear.

According to study results, an optimal therapeutic option for the treatment of acutely decompensated heart failure is yet to come.

Source: American Heart Journal, 2006


XagenaMedicine2006