Subgroup aged < 65 years 1.42 0.197 Subgroup aged 65 years 1.12 Subgroup aged < 70 years 1.33 0.355 Subgroup aged 70 years 1.11 Symptomatic bradycardia Overall study population 5.46 Subgroup aged < 65 years 6.64 0.352 Subgroup aged 65 years 4.53 Subgroup aged < 70 years 5.62 0.800 Subgroup aged 70 years 5.07 Asymptomatic bradycardia Overall study population 4.18 Subgroup aged < 65 years 4.14 0.925 Subgroup aged 65 years 4.23 Subgroup aged < 70 years 3.97 0.651 Subgroup aged 70 years 4.72 Blood pressure inadequately controlled Overall population 1.18 Subgroup aged < 65 years 1.05 0.175 Subgroup aged 65 years 1.37 Subgroup aged < 70 years 1.09 0.187 Subgroup aged 70 years 1.48 Responses to clinical questions raised in first evaluation The clinical questions that were raised in the first CER followed by the evaluator’s comments on the sponsor’s responses are shown below. Question relating to Efficacy: Please provide additional efficacy and safety analyses results on the primary composite endpoint and the secondary endpoints for the subgroup of patients in the RSBBdose population who were aged 65 years. In the main analyses, there appeared to be a lower effect of ivabradine on those aged 65 years in the RSBBdose population. In the pre-specified subgroup analysis in the RSBBdose population on the primary composite endpoint and on the secondary endpoint of hospitalisation for worsening heart failure, results showed an effect in favour of ivabradine in all the pre-specified subgroups except for the subgroup 65 years”. “age
Subgroup aged < 65 years Subgroup aged 65 years 1.42 1.12 0.197 Subgroup aged < 70 years Subgroup aged 70 years 1.33 1.11 0.355 Symptomatic bradycardia Overall study population 5.46 Subgroup aged < 65 years Subgroup aged 65 years 6.64 4.53 0.352 Subgroup aged < 70 years Subgroup aged 70 years 5.62 5.07 0.800 Asymptomatic bradycardia Overall study population 4.18 Subgroup aged < 65 years Subgroup aged 65 years 4.14 4.23 0.925 Subgroup aged < 70 years Subgroup aged 70 years 3.97 4.72 0.651 Blood pressure inadequately controlled Overall population 1.18 Subgroup aged < 65 years Subgroup aged 65 years 1.05 1.37 0.175 Subgroup aged < 70 years Subgroup aged 70 years 1.09 1.48 0.187 Responses to clinical questions raised in first evaluation The clinical questions that were raised in the first CER followed by the evaluator’s comments on the sponsor’s responses are shown below. Question relating to Efficacy: Please provide additional efficacy and safety analyses results on the primary composite endpoint and the secondary endpoints for the subgroup of patients in the RSBBdose population who were aged 65 years. In the main analyses, there appeared to be a lower effect of ivabradine on those aged 65 years in the RSBBdose population. In the pre-specified subgroup analysis in the RSBBdose population on the primary composite endpoint and on the secondary endpoint of hospitalisation for worsening heart failure, results showed an effect in favour of ivabradine in all the pre-specified subgroups except for the subgroup “age 65 years”.