Use Instructions

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The incidence of overall non-serious adverse events was significantly higher in the OPTIMIZER
subject cohort of the FIX-HF-5C2 study than for the control group of the FIX-HF-5C study. It was
not significantly greater than the incidence on non-serious adverse events in the OPTIMIZER
group for the FIX-HF-5C study. The higher rate between the FIX-HF-5C2 OPTIMIZER subjects
and subjects in the control group for FIX-HF-5C can be attributed to differences in general
medical events and localized infection. General medical events include a wide range of adverse
events such as sore throats to more serious events like cholelithiasis. Clinically, it is difficult to
interpret the meaning of any differences in general medical events. Only 1 of the 5 non-serious
localized infections was device related (IPG pocket). The important point is that the localized
infection rate was not high to begin with and was not significantly different between the
OPTIMIZER subjects for the FIX-HF-5C2 study and the OPTIMIZER subjects for the FIX-HF-5C
study.
Discussion
The study met its primary effectiveness endpoint based on the Bayesian analysis presented
which was supported by frequentist analyses. With respect to safety, there were no device-
related complications and only 1 procedure-related complication (<2%). This was significantly
lower than the rate observed in the FIX-HF-5C 3-lead device study. There was no evidence of a
difference between study groups with respect to adverse events or adjudicated serious adverse
events, although the FIX-HF-5C2 OPTIMIZER group appeared to have a lower rate of serious
OPTIMIZER System related events than was seen previously.
Thus, it can be concluded that the FIX-HF-5C2 study met its pre-specified endpoints and that the
2-Lead configuration of the OPTIMIZER Smart is at least as safe and effective as the 3-Lead
configuration of the OPTIMIZER Smart approved by FDA in P180036.
Peak VO2 improved more in the OPTIMIZER patients of the present FIX-HF-5C2 study than in
the prior FIX-HF-5C study control group for both Bayesian and frequentist statistical analyses.
Risk-Benefit
The benefits of the 2-Lead configuration of the OPTIMIZER Smart are an improvement in peak
VO2, improved functional status as evidenced by improvements in NYHA functional class and a
reduced incidence of procedural complications as compared to the 3-Lead configuration of the
OPTIMIZER Smart (FIX-HF-5C study). Risks associated with the OPTIMIZER Smart system are
similar to those associated with ICDs and pacemakers; which are well documented in the
literature. In the FIX-HF-5C2 study, lead dislodgments were the primary complication reported.
There were no lead dislodgments reported in the FIX-HF-5C2 study. Thus, it is clear that the
potential benefits of the 2-Lead configuration of the OPTIMIZER Smart outweigh the potential
risks.
Conclusions
Based on the results of the FIX-HF-5C2 study described herein, we conclude the following:
1. The 2-Lead configuration of the OPTIMIZER Smart System is safe and effective for the
delivery of CCM therapy in patients with NYHA class III heart failure symptoms.
2. Exercise tolerance as evidenced by improved peak VO2, is improved by CCM therapy
delivered by the 2-Lead configuration of the OPTIMIZER Smart system.
3. CCM therapy delivery with the 2-Lead system is clinically effective and the same as
delivery with the 3-Lead device.
4. Complication rates are lower with the 2-Lead device possibly due to the reduction in the
number of implanted leads.
5. The serious adverse event profile for the 2-Lead device is not significantly different from
that with the 3-Lead device.