AusPAR: Ivabradine - Therapeutic Goods Administration

AusPAR Coralan Ivabradine Servier Laboratories (Australia) Pty Ltd PM-2010-03269-3-3
Final 31 October 2012
Therapeutic Goods Administration
Subgroup analysis of the secondary endpoints relating to mortality (death from any
cause, cardiovascular death and death from heart failure) in the RS population showed an
effect in favour of ivabradine in all the pre specified subgroups except in the subgroup of
“baseline HR 0.05 in all pre-specified subgroups except for the subgroup on baseline HR (< 77 bpm
versus ≥77 bpm), with p=0.0274 and p=0.0379 for each endpoint, respectively, showing a
greater effect of ivabradine on the subgroup with baseline HR of ≥77 bpm than that with
baseline HR of < 77 bpm. Analysis in the subgroup “age ≥ 75 years” (n = 722) was only
presented for the endpoint of cardiovascular death and also showed an effect in favour of
ivabradine, with an estimated hazard ratio of 0.71 (95% CI [0.51, 1.00]). No analysis for
statistical significance was presented.
For endpoints relating to hospitalisation (hospitalisation for any cause, hospitalisation for
cardiovascular reason and hospitalisation for worsening heart failure), only subgroup
analysis on hospitalisation for worsening heart failure was presented in the CSR and
showed an effect in favour of ivabradine in all the pre specified subgroups. Subgroup
interaction tests on the endpoint of hospitalisations for worsening heart failure yielded pvalues
>0.05 in all pre specified subgroups except for the subgroup on ischaemic versus
non-ischaemic cause, with p=0.0345, showing that ivabradine had a statistically
significantly greater effect on patients with CHF from an ischaemic cause compared to
those with CHF from a non-ischaemic cause. Analyses on hospitalisation for worsening
heart failure in the subgroup “age ≥75 years” also showed an effect in favour of ivabradine,
with a hazard ratio of 0.92 (95% CI [0.68, 1.23]). No analysis for statistical significance
was presented. 25
Analysis in the RSBBdose population of the secondary endpoints relating to mortality
showed that differences between treatment groups in the endpoints of deaths from heart
failure, cardiovascular deaths and death from any cause were all found to be not
statistically significant (p=0.438 to 0.986) (Tables 6 and 7). Analysis in the RSBBdose
population of the secondary endpoints relating to hospitalisations showed that differences
between treatment groups in the endpoints of hospitalisation for worsening heart failure
and cardiovascular hospitalisation were statistically significant in favour of ivabradine
(hazard ratios of 0.81 [p= 0.0211] and 0.88 [p=0.0464], respectively) but that for
hospitalisation for any cause was not statistically significant (p=0.081) (Tables 8 and 9).
25 Sponsor comment: “95% confidence intervals were indeed presented demonstrating no statistical
significance.”
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