Sunday, January 01, 2006

Top 10 issues in hospital medicine for 2005------issue 2

The Natrecor controversy

Nesiritide (Natrecor) was approved in 2001 for intravenous treatment of acutely decompensated heart failure. Short term results in the VMAC study showed superiority over nitroglycerine, mainly in terms of wedge pressure reduction, with more modest improvement in clinical endpoints. The drug appeared promising for rapid reversal of acute severe decompensation of heart failure and had a better safety profile than dobutamine.

Controversy was sparked, however, with the publication of this pooled analysis in JAMA last April which suggested a trend toward increased 30 day mortality with the use of Nesiritide. Opinion writers and bloggers reacted with harsh criticism of the makers of Natrecor for their promotions, and many called for a ban of its use.

How can we put the findings of the pooled analysis in perspective? First of all it must be noted that of 12 randomized controlled trials of Neseritide only 3 were chosen for inclusion in the analysis and the results were driven mainly by one study (PROACTION) which looked only at the use of Nesiritide in emergency department observation units. Moreover, the trend toward increased mortality was not statistically significant. Nesiritide’s effects on mortality deserve systematic study, and pending the results of such studies it should be used with caution. Nitroglycerine may be a safer alternative. In considering adjunctive infusion treatments alongside intravenous diuretics for acutely decompensated heart failure Nesiritide might occupy a position on the hierarchy between nitroglycerine and inotropes. The swift and contentious reactions to the paper were surprising and, in my view, irresponsible. For over a decade it was known that dobutamine was associated with increased mortality, yet clinicians continued to use it. Where was the outrage?

A reasoned and balanced recommendation on Natrecor is contained in this document from an expert panel chaired by Eugene Braunwald. Any clinician with an interest in treating acute heart failure should be thoroughly familiar with this report.


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