Randomised study of effect of ibopamine on survival in patients with advanced severe heart failure. Second Prospective Randomised Study of Ibopamine on Mortality and Efficacy (PRIME II) Investigators.

BACKGROUND

Drugs that improve symptoms in patients with heart failure must also be assessed for their effects on survival. Ibopamine stimulates DA-1 and DA-2 receptors and causes peripheral and renal vasodilatation; the drug improves symptoms of heart failure. We assessed the effect of ibopamine on survival in patients with advanced heart failure in a multicentre, randomised placebo-controlled study.

METHODS

Patients with advanced severe heart failure (New York Heart Association classes III and IV) and evidence of severe left-ventricular disease, who were already receiving optimum treatment for heart failure, were randomly allocated oral ibopamine 100 mg three times daily or placebo. The primary endpoint was all-cause mortality. The study was designed to recruit 2200 patients, and the minimum duration of treatment would be 6 months. We did intention-to-treat and on-treatment analyses; a post-hoc subgroup analysis was also done.

FINDINGS

After we had recruited 1906 patients the trial was stopped early, because of an excess of deaths among patients in the ibopamine group. 232 (25%) of 953 patients in the ibopamine group died, compared with 193 (20%) of 953 patients in the placebo group (relative risk 1.26 [95% CI 1.04-1.53], p = 0.017). The average length of follow-up was 347 days in the ibopamine group and 363 days in the placebo group. In multivariate analysis, only the use of antiarrhythmic drugs at baseline was a significant independent predictor of increased fatality in ibopamine-treated patients.

INTERPRETATION

Ibopamine seems to increase the risk of death among patients with advanced heart failure who are already receiving optimum therapy, but the reasons for this increase are not clear. Our finding that antiarrhythmic treatment was a significant predictor of increased mortality in ibopamine-treated patients may be important, but exploratory analyses must be interpreted with caution.