Use Instructions

58
Baseline heart failure medications are summarized in Table 14. The only significant
differences were a greater use of ARNi’s, anti-arrhythmics, and anticoagulants in FIX-
HF-5C2 subjects. The greater ARNi use reflects the fact that they were introduced
toward the end of the FIX-HF-5C study. The greater use of anti-arrhythmics and
anticoagulants likely represents the inclusion of patients with atrial fibrillation; those
patients were excluded in the FIX-HF-5C study. Table 15 breaks down the anti-
arrhythmic medication usage in FIX-HF-5C2 and FIX-HF-5C studies for comparison.
Table 15: Baseline Anti-arrhythmic Medications
FIX-HF-5C2
FIX-HF-5C
Variable
OPTIMIZER
OPTIMIZER
Control
Anti-arrhythmic
19 (31.7%)
14 (18.9%)
12 (14.0%)
Amiodarone
12 (20.0%)
11 (14.9%)
6 (7.0%)
Sotalol
5 (8.3%)
3 (4.1%)
2 (2.3%)
Mexiletine
1 (1.7%)
0
3 (3.5%)
Dofetilide
1 (1.7%)
0
1 (1.2%)
Primary Effectiveness Endpoint
Bayesian Analysis
A Bayesian repeated measures model was used to estimate group differences in the
mean peak VO
2
at 24 weeks from baseline in FIX-HF-5C2 device patients compared
to FIX-HF-5C control patients, with 30% borrowing of information (70% down-
weighting) from the corresponding group difference observed in the FIX-HF-5
subgroup data.
In the FIX-HF-5C2 device group, 55 of the 60 patients provided at least one post-
baseline peak VO
2
measurement, and 52 patients provided 24-week peak VO
2
measurements. There were no deaths in FIX-HF-5C2 subjects at the 24-week
assessment period, and there were no missing observations due to heart failure
hospitalizations. However, patients in the FIX-HF-5C control group who are missing
peak VO
2
observations due to death are imputed as zeros per the FIX-HF-5C
protocol. There are a total of 146 patients and 397 non-missing peak VO
2
observations in the combined FIX-HF-5C2 device and FIX-HF-5C control groups for
this analysis.
Tables 16 and 17 provide results of the Bayesian analyses while Figures 4 and 5
show the peak VO2 results graphically.
Table 16: Number of Observations, Mean, SD of Peak VO2 by Group and Time
Nobs (observed)
Nobs (missing)
Mean
Standard Deviation
Control
Device
Control
Device
Control
Device
Control
Device
Baseline
86
60
0
0
15.36
15.01
2.81
2.94
12 Weeks
73
52
13
8
14.59
16.01
4.29
3.34
24 Weeks
74
52
12
8
14.34
16.22
4.69
3.09
Table 17: Bayesian Primary Analysis Results (with Borrowing)
Borrowing (Bayes)
Time
TmtDiff
LL
UL
SE
P(Superior)
12 Weeks
1.079
0.381
1.776
0.356
0.999
24 Weeks
1.722
1.021
2.417
0.356
1.000