AHA: Novel Drug May Speed Improvement in Patients With Severe Heart Failure

DALLAS, Nov. 14 - Hospitalized patients with decompensated heart failure may stabilize faster if levosimendan, an investigational calcium sensitizer, is added to standard treatment, researchers reported today.
Action Points
Advise patients that this is a report about an investigational drug that is not yet clinically available.
This study was published as an abstract and presented at a conference either as an oral or poster presentation. These data and conclusions should be considered to be preliminary as they have not yet been reviewed and published in a peer-reviewed publication.
Levosimendan appears to increase myofilament calcium sensitivity by binding to cardiac troponin C in a calcium-dependent manner. This stabilizes the calcium-induced conformational change of troponin C, causing an increase in tension development and myocardial contractility.
Patients randomized to 24-hour levosimendan infusion, a drug which is marketed in other countries under the name Simdax, had a significant 33% higher likelihood of clinical improvement than patients in the placebo arm, said Milton Packer, M.D., of University of Texas Southwestern in Dallas.
Moreover, the likelihood of clinical deterioration was 26% lower in the levosimendan arm than in the placebo arm, which was also significant (p=0.015 for both), Dr. Packer reported at the American Heart Association meeting here.
REVIVE II, a multicenter, placebo-controlled trial of levosimendan on clinical status in acutely decompensated heart failure, randomized 299 patients to the study drug and 301 to placebo. All patients received standard IV heart failure therapy including inotropic agents and vasodilators.
As in most heart failure studies the primary endpoint was a soft composite, such as lessening of symptoms, and hard-death or need for additional interventions.
After five days both the placebo and levosimendan groups were "pretty much in the same place," said Gordon Tomaselli, M.D., of Johns Hopkins. "They were clinically stable, but the patients in the levosimendan group got to that point faster,"
He added, however, that "this study did not demonstrate that the drug reduced mortality." Dr. Tomaselli, vice-chairman of the AHA Scientific Sessions program committee, chaired an AHA press conference where the REVIVE II results were discussed. He said a second levosimendan trial will be presented Wednesday and that study will report mortality data.
Among the findings reported today:
7% of levosimendan patients had worsening dyspnea versus 12% of placebo patients;
Pulmonary edema increased in 2% of levosimendan patients versus 6% of placebo patients and
2% of levosimendan patients had decreased mental status versus 1% of placebo patients.
The study was funded by Abbott Laboratories in Chicago and Orion Pharma in Helsinki, Finland, which are collaborating on the development of the drug.
Primary source: American Heart Association Scientific Sessions 2005Source reference: Packer M et al "REVIVE II Multi-center placebo-controlled trial of levosimendan on clinical status in acutely decompensated heart failure." PS 03 November 14, 2005