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Vasopressin Antagonists: Another Class of Heart Failure Drugs?

Tolvaptan improved diuresis without adversely affecting vital signs, potassium levels, or renal function.

Heart failure patients' elevated vasopressin levels might exacerbate their congestive symptoms. Researchers conducted a multicenter, phase 2 feasibility trial of tolvaptan, a selective vasopressin receptor antagonist. They randomized 319 patients who were hospitalized with worsening heart failure to receive standard therapy plus once-daily oral doses of either tolvaptan (at 30, 60, or 90 mg) or placebo. All subjects had ejection fractions <40% and persistent signs or symptoms of congestion despite standard therapy.

By 24 hours after randomization, median body weight had decreased significantly more in the three tolvaptan groups than in the placebo group (by 1.8-2.1 kg vs. 0.6 kg). Tolvaptan therapy did not adversely affect blood pressure, heart rate, potassium levels, or renal function. The rate of worsening heart failure at 60 days was similar in tolvaptan and placebo recipients. In a post hoc analysis, patients with severe systemic congestion and renal dysfunction showed a significant 60-day survival benefit with tolvaptan.

Comment: In heart failure patients, tolvaptan improved diuresis, presumably by interfering with the vasoconstrictive and detrimental hemodynamic effects of vasopressin elevation. Editorialists acknowledge concerns that selective vasopressin antagonists, which act on only some vasopressin receptors, might increase interaction between vasopressin and other receptors, leading to vasoconstriction and increased afterload. Tolvaptan's lack of detrimental effects on vital signs, potassium levels, and renal function in this trial mitigates such concerns. A phase 3 trial will clarify whether a "vaptan" really can improve clinical outcomes in heart failure patients.

— Kirsten E. Fleischmann, MD, MPH

Published in Journal Watch General Medicine June 4, 2004

Citation(s):

Gheorghiade M et al. Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: A randomized controlled trial. JAMA 2004 Apr 28; 291:1963-71.

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Francis GS and Tang WHW. Vasopressin receptor antagonists: Will the "vaptans" fulfill their promise? JAMA 2004 Apr 28; 291:2017-8.

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