We thank Dr Prabhath for his interest in our paper (1). The question
tested in the paper is that of equivalence of 2 strategies in patients
with acute heart failure, previously receiving beta-blocker therapy for
more than 3 months, in terms of functional improvement at day 3.
They question the value of the absence of placebo in this study. We
agree that a placebo controlled trial is more convincing that an open
labeled trial, but for practical reasons, placebo controlled trial would
have been very difficult: all the patients were not receiving the same
beta-blocker at the same dosage before entering the hospital, so that the
placebo would have been difficult to make. In the absence of blinding, the
placebo is probably useless.
The statistical methods used for the necessary population size are
standards. The sample size required in a noninferiority trial is
determined by the noninferiority margin and the expected success rates in
each treatment groupe. Hence, the sample size required can be large or
moderate, depending on the hypotheses. Here, one of the reason of a
moderate sample size is the high expected success rate (90%) that conducts
to a low standard deviation of the difference between the two groups.
The choice of non-inferiority margin is not based on any meta-
analysis as no previous study of this kind has been performed. It has been
chosen because 1) it is the value usually accepted for non inferiority
studies performed when evaluating a drug (2) 2) 12.5% appears to be an
acceptable value from a clinical point of view. It should be stressed
however, that the main endpoint of the study is not the appearance of a
clinical event, but the functional improvement of the patient at day 3
after an acute decompensation. It was felt that delayed improvement (with
as a possible consequence worse prognosis) was the main concern if beta-
blockers were to be pursued. When Dr Prabhath is referring to non
inferiority trial with large number of patients, he probably refers to
studies in which endpoints are clinical events.
Actually, pursuing the beta-blocker therapy during acute
decompensation did not delay functional improvement and was associated
with more patients receiving beta-blocker therapy after 3 months. We hope
that these comments will help Dr Prabhath and other to B-CONVINCED.
Guillaume JONDEAU. AP-HP, Hôpital Bichat, Service de Cardiologie,
Faculté de médecine Paris VII, INSERM U698, Paris F-75018.
Marie Laure TANGUY, Philippe LECHAT. AP-HP, Unité de Recherche Clinique,
Pitié Salpêtrière, F-77013 Paris, France
Reference
(1)Jondeau G, Neuder Y, Eicher JC, Jourdain P, Fauveau E, Galinier M,
Jegou A, Bauer F, Trochu JN, Bouzamondo A, Tanguy ML, Lechat P; B-
CONVINCED Investigators. B-CONVINCED: Beta-blocker CONtinuation Vs.
INterruption in patients with Congestive heart failure hospitalizED for a
decompensation episode. Eur Heart J. 2009 Sep;30(18):2186-92.
(2) Pfeffer MA, McMurray JJ, Velazquez EJ, Rouleau JL, Køber L,
Maggioni AP, Solomon SD, Swedberg K, Van de Werf F, White H, Leimberger
JD, Henis M, Edwards S, Zelenkofske S, Sellers MA, Califf RM; Valsartan in
Acute Myocardial Infarction Trial Investigators Valsartan, captopril, or
both in myocardial infarction complicated by heart failure, left
ventricular dysfunction, or both. N Engl J Med. 2003 Nov 13;349(20):1893-
906.
Conflict of Interest:
None declared
