|
Ou comment g�cher une bonne id�e.
Par ailleurs, le congr�s ACC a l'air bien
stimulant.
Alain
----- Original Message -----
However, doctors listening to the presentation had their reservations about
the results
Nevertheless, one heart-failure expert, Dr John Cleland (University of Hull, UK) commented to heartwire , "Although we need to be a little bit cautious, there is accumulating evidence in favor of levosimendan; the data are beginning to look consistent." Current treatment for acute heart failure unsatisfactoryCurrent treatment for acute decompensated heart failure
The only previous study of levosimendan in acute decompensated heart failure, the LIDO trial,[ 1] showed that the new drug was superior to dobutamine in improving mortality at six months, he noted. "But there was no placebo arm in this study and there were concerns that the superiority of levosimendan may simply reflect the inferiority of dobutamine," he explained.
CASINO was due to enroll 600 patients hospitalized with NYHA class 4 heart failure who were randomized to levosimendan, dobutamine, or placebo 48 hours after presentation. The primary end point of the study was mortality at one month, six months, or one year, whichever occurred first.
The study was stopped prematurely when 299 patients were enrolled, because of a clear mortality benefit of levosimendan, Zairis explained. Of the 299 patients, eight withdrew, so 98 received levosimendan (bolus dose of 16 mcg over 10 minutes followed by 0.2 mcg/kg per min for 24 hours), 96 received dobutamine (placebo bolus then 10 mcg/kg per min for 24 hours), and the remaining 97 got placebo. A bolus dose is required with levosimendan because of its short half-life of one hour, Zairis told heartwire .
Cardiac death at one-month and six-month follow-up
Dobutamine is detrimental"Intravenous levosimendan showed a significant survival benefit while dobutamine actually increased mortality," Zairis said. The p value for the benefit of levosimendan vs placebo was only 0.04, however, and doctors listening to the presentation were concerned that the analysis was done on-treatment instead of by intention-to-treat, commenting that if the eight patients who withdrew were included this may have altered the p value. "We really critically have to know what happened to those patients," one said.
Zairis was unable to say what happened to the eight patients, but he told heartwire that he now routinely uses levosimendan in acute hospitalized heart-failure patients in Greece. Cleland also said, "If levosimendan were available in the UK I would be using it because there is evidence that it is safer than any other IV agent." Cleland added that he does not use dobutamine or any other inotropic agents in these patients. "In fact, we did a meta-analysis and we found that dobutamine significantly increases mortality in these patients."
Cleland told heartwire that there are two other ongoing levosimendan studies: a European trial, SURVIVE, comparing levosimendan with dobutamine, and a US study, REVIVE, comparing levosimendan with placebo. "Both of these have already recruited more patients than CASINO," he noted, and will be completed within the next 18 months.
Levosimendan was first approved in Sweden in 2000 and is available in most Mediterranean countries, including Greece, and several markets in South America. Applications for the drug in the US, France, Germany, the UK, and some other EU markets were withdrawn but will be resubmitted when the results of the SURVIVE and REVIVE studies become available.
| |||||||||||||||||||||||||||||||||||||||
