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(Circulation. 2001;103:e94.)
© 2001 American Heart Association, Inc.

Correspondence

Acute Endothelin A Receptor Blockade in Heart Failure

Alison Seed; John McMurray

Clinical Research Initiative in Heart Failure, University of Glasgow, Glasgow, Scotland

To the Editor:

We were surprised by the findings of Givertz et al and their interpretation.¹

These authors describe the acute (6-hour) hemodynamic effects of 3 doses of the intravenous endothelin (ET) A receptor-selective antagonist sitaxsentan, compared with placebo, in patients with severe chronic heart failure. The patients studied had a strikingly high pulmonary vascular resistance (PVR) and mean pulmonary artery pressure compared with those in similar studies of other ET-1 receptor antagonists.^{2 3 4 5} Sixteen patients received placebo, 8 received sitaxsentan 1.5 mg/kg, 16 received sitaxsentan 3.0 mg/kg, and 8 received sitaxsentan 6.0 mg/kg.

Curiously, the 1.5 mg/kg and 3 mg/kg doses seemed to have greater hemodynamic effects than the 6 mg/kg dose. The peak effect occurred at 2 to 4 hours. Although only the pulmonary vascular effects were statistically significant, there was also an apparent reduction in systemic vascular resistance (SVR) by 19% 2 hours after the 3 mg/kg dose compared with a 34% reduction in PVR at this time after the same dose.

The only other published, placebo-controlled study of this type used the nonselective (ET_A/B) ET-1 receptor antagonist bosentan.² In that study, 24 patients received intravenous placebo or 100 mg of bosentan followed by placebo or 200 mg of bosentan, respectively, 1 hour later. The average reductions in PVR and SVR 2 hours after dosing were 33% and 17%, which are remarkably similar to the findings in the sitaxsentan study (although both SVR and PVR were reduced significantly after bosentan). Consequently, it is hard to support the . . . [Full Text of this Article]

Michael M. Givertz, MD; Wilson S. Colucci, MD

Section of Cardiovascular Medicine, Boston University Medical Center, Boston, Mass

Thierry H. LeJemtel, MD

Albert Einstein College of Medicine, Bronx, NY

Stephen S. Gottlieb, MD

University of Maryland, Baltimore, Md

Joshua M. Hare, MD

Johns Hopkins Medical Institutions, Baltimore, Md

Mara T. Slawsky, MD, PhD

Boston Veterans Affairs Medical Center, Boston, Mass

Carl V. Leier, MD

Ohio State University, Columbus, Ohio

Evan Loh, MD

University of Pennsylvania, Philadelphia, Pa

John M. Nicklas, MD

University of Michigan, Ann Arbor, Mich

Bruce E. Lewis, MD

Loyola University, Maywood, Ill