Levosimendan proves safe and effective in end-stage heart failure

Levosimendan proves safe and effective

According to a study presented at the Heart Failure Congress 2013,  levosimendan, a calcium sensitiser, improves event free survival by 50% compared with placebo in patients with end stage cardiac failure. Furthermore, another study showed that the third generation mineralocorticoid receptor antagonist (MRA) BAY 94-8862 is effective in patients with chronic kidney disease and heart failure. Levosimendan is a drug that increases heart sensitivity to calcium, which means that it increases cardiac contractility without increasing the level of calcium in the heart. Besides the positive inotropic effect, levosimendan also has vasodilatory effect (because it acts on potassium channels and induces smooth muscle relaxation) and a cardioprotective effect.

Management of patients with congestive heart failure is difficult on the one hand because each patient responds individually to treatment and on the other hand because patients usually have multiple comorbidities (kidney disease, liver disease, digestive diseases associated etc). Therefore, researchers conducted a multicenter study (LevoRep)  to investigate the efficacy and safety of levosimendan, a calcium sensitiser, in patients with congestive heart failure. It should be noted that LevoRep is the largest study of ambulatory administration of an inotrope drug in patients with end-stage heart failure.

Drugs

The study included 120 patients with congestive heart failure who received biweekly either levosimendan (0.2 mcg / kg / min for 6 hours) or placebo. Results showed that levosimendan administered ambulatory was safe and effective in patients with end stage cardiac failure because it improved event free survival by 50% compared with placebo. This was the secondary endpoint of the study. However, it must be said that in terms of functional capacity and quality of life, levosimendan did not bring benefits. In other words the primary endpoints of the study were not met. Dr Gerhard Poelzl (Austria) said the further studies with more patients and with higher doses or higher repetition frequencies of levosimendan, could have positive results in terms of primary endpoints.

Another study was a randomized, double-blind,  phase 2 trial (MinerAlocorticoid Receptor Antagonist Tolerability Study) conducted on patients with chronic heart failure and chronic kidney disease. First and second generation of MRA have limited indications in such patients because of side effects (hyperkalemia, worsening renal function). However, the third generation MRA (BAY 94-8862) is considered to be less harmful to the kidneys. Study results showed that BAY 94-8862 is safe and well tolerated regardless of the dose used (2.5, 5, or 10 mg once daily or 5 mg twice daily). Professor Faiez Zannad (France) added that: “Future studies will investigate BAY 94-8862 novel indications: patients with heart failure and either moderate CKD or diabetes hospitalized for worsening chronic heart failure, and kidney protection in diabetics.”