clinical trial results 20th dec 2007, page-2

tks

Discussion
This is the first report that summarises the efficacy and
safety profile of the VentrAssistTM LVAD, based on data from
an international, multicentre clinical trial. This report also
presents an update on the ongoing clinical deployment of the
VentrAssistTM LVAD across Europe, Australasia and USA, with
summaries provided of the completed, ongoing and planned
clinical trials.
In the CE Mark trial, the primary efficacy outcome
measure (survival until transplant or transplant-eligibility)
was achieved by 83% of patients implanted with a
VentrAssistTM. This result compares favourably with published
reports of 65—70% of patients achieving survival to
transplant success with other LVADs [13]. The success rate
achieved with the VentrAssistTM in the multicentre CE Mark
trial is particularly notable given that each centre had to
progress through an inevitable ‘learning curve’. As an
example of the ability for each centre to develop proficiency
with the VentrAssistTM, tamponade events were confined to
the first half of the study.
Morbidity and mortality association with anticoagulation
management of patients with mechanical support continues
to challenge clinicians. The anticoagulation prophylaxis
regimen used in the completed trials was relatively simple;
the INR was monitored and acetylsalicylic acid used
empirically. The INR level was relatively modest, compared
to that recommended for other devices [15,16]. Despite the
low levels of anticoagulants used, perioperative bleeding was
an issue in early patients, and two of the five deaths in the CE
Mark trial were associated with bleeding. Paradoxically, some
patients required surgery for non-LVAD related conditions
following implant and anticoagulation was suspended, without
incident, for periods of up to 1 week. This may indicate
that the anticoagulation regimen could perhaps be tailored
for individual patients and changing medical conditions,
rather than the empirical level of anticoagulation thought to
be ‘required’ for the LVAD.
The ultimate demand for LVADs is thought to be as a
permanent form of mechanical assistance. The demand for
permanent assistance reflects the mismatch between
transplant organ availability and the increasing incidence
of heart failure in the aging population, in both developed
and developing countries, the increasing prevalence of risk
factors for heart failure and the supply—demand imbalance
in clinical heart transplantation [17]. In this respect, the
results reported thus far after a relatively short follow-up
period can only begin to indicate whether the VentrAssistTM is
suitable for long-term use. However, the low linearised rate
of SAEs after implant and the absence of mechanical failure
auger well for longer implant durations. Confidence in the
VentrAssistTM system has also been strengthened by the fact
that none of the early patients in the pilot trial died as a
result of device failure or malfunction and also by the
successful outcomes in the home discharge cohort. The
VentrAssistTM LVAD represents one of the new generation of
smaller, potentially more reliable, ‘next-generation’ LVADs.
These LVADs may make long-term circulatory assist available
to a wider range of the heart failure population; particularly
those who are non-transplant eligible or those with smaller
body habitus. The ongoing and forthcoming clinical trials will
provide more definitive data regarding the long-term
therapeutic potential of the VentrAssistTM LVAD.
5. Conclusion
The number of implants with the VentrAssistTM has now
surpassed that of any other third-generation centrifugal
device. A pilot trial with the VentrAssistTM showed the
potential of the device in a broad spectrum of challenging
heart failure patients. A prospective, multicentre, international
clinical trial has confirmed the favourable efficacy and
safety profile of the VentrAssistTM patients. The Clinical
Development Plan for the VentrAssistTM currently comprises
seven clinical trials; data from these trials have and will be
used in international regulatory submissions and ongoing
post-market surveillance studies.