November 14th, 2010
ASCEND-HF: Nesiritide Is Safe But Not Effective
ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure Trial) was started in response to the enormous controversy over the safety and efficacy of nesiritide, which was being used in growing numbers of heart failure patients. The trial randomized 7141 patients with acute, decompensated HF to receive standard therapy and either continuous intravenous nesiritide or placebo.
Results of ASCEND-HF, presented as a late-breaking clinical trial at the AHA meeting, showed that there were no significant differences in the pre-specified endpoint of dyspnea. Shortness of breath improved in 15.0% of nesiritide patients and 13.4% of placebo patients. At 24 hours, the pattern was similar: 30.4% of nesiritide patients and 27.5% of placebo patients had improved breathing function. At 1 month, the rate of all-cause mortality and hospital readmission for HF did not differ statistically between the groups (9.4% with nesiritide and 10.1% with placebo).
Although the early controversy over nesiritide was fueled by concerns that the drug might cause an increase in mortality or renal damage, the ASCEND-HF investigators found no evidence to support these concerns.
In an AHA press release, study chair Robert Califf said:
“Nesiritide was marketed and widely used in the U.S. because of a perception that it had a major effect on dyspnea and then largely abandoned in clinical use because of concerns that it might increase rates of death and renal failure. Now that we finally have a proper clinical trial we know that both perceptions were incorrect; nesiritide is safe but has only a modest effect on dyspnea. This is a major signal that we must do a better job defining the biological effects of drugs early in development and conduct adequately powered outcomes trials much earlier to give doctors and patients the necessary information to enable appropriate use of the treatment in practice.”
Said trial investigator Adrian Hernandez: “I think the main message is that we need to do adequately powered studies to really understand the balance of safety and effectiveness. Now that we’ve done an adequate trial, we know that nesiritide can be used safely, but there is no mandate to use it because of its modest effects.”
One investigator, Randall Starling, did not rule out the use of nesiritide in some patients: “Given the complexities of heart failure, there is a significant need for better medications for use in treatment. With the safety questions related to nesiritide having now been addressed, it could be an option for physicians depending on their interpretation of clinical benefit.
Note: The AHA 2010 presentation slides for ASCEND-HF can be found on the Duke Clinical Research Institute website.