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Two trials of stem cells
fail tomeet primary
endpoints but improve
health status
Two trials of
regenerative therapy
for heart failure failed
to meet their primary
endpoints but brought
clinically relevant
benefits.
Trial 1: A phase 2, randomised, single-
blind, placebo-controlled, crossover,
multicentre study
Javed Butler MD, of The State University of New
York at Stony Brook, reported on the first trial.
He and a colleague delivered a single dose of
mesenchymal stem cells intravenously to patients
with chronic nonischaemic cardiomyopathy.
Significant cardiac structural or functional
improvement did not occur but several clinically
relevant benefits were observed.
Dr Butler said the trial “demonstrated that a more
convenient and less invasive infusion strategy is
safe, well-tolerated and shows improvements in
multiple measurements of patient health status.”
Previous work in this field has focused almost
exclusively on the more invasive approach of
injecting stem cells directly into the heart.
Dr Butler and his colleague used “ischaemia
tolerant” mesenchymal stem grown under chronic
hypoxic conditions, with the aim of enhancing their
potential benefits.
He explained, “The premise was that stem cells may
exert immune modulatory properties, which are
enhanced when grown under hypoxic conditions.”
This potential immune modulation and anti-
inflammatory effect also opens the door to new
methods of delivery.
“Virtually all studies of stem cell therapy for heart
failure have centred on the concept that the
cells must be injected directly into the heart to
trigger new growth, but if stem cells yield anti-
inflammatory benefits, direct cardiac delivery
may not be necessary to repair and stimulate the
dysfunctional viable myocardium.”
Patients with nonischaemic cardiomyopathy and left
ventricular ejection fraction
≤
40% were randomised
to intravenous ischaemia-tolerant mesenchymal
stem cell therapy (n=10) or placebo (n=12) for 90
days and then crossed over to the other treatment.
Stem cells were donated by a health volunteer and
grown under hypoxic conditions from the moment
of extraction.
At 90-days post infusion, no major differences in
primary safety endpoints of all-cause mortality,
all-cause hospitalisation, and adverse events were
observed.
Secondary endpoints of cardiac remodelling
(left ventricular ejection fraction and ventricular
volumes), assessed by cardiac magnetic resonance
imaging, did not differ between groups at 90-
days. Ischaemia-tolerant mesenchymal stem
cell administration did result in the secondary
endpoints of better health status and functional
capacity, however.
Specifically, compared with placebo, ischaemia-
tolerant mesenchymal stem cell therapy resulted in
statistically significant improvements in 6-minute
walk test (an estimated 36 m more than placebo,
P = 0.02) and Kansas City Cardiomyopathy
Questionnaire scores (clinical summary score
+5.22, P = 0.02, and functional status scores
+5.65, P = 0.06) at 90-days post infusion.
Additionally, ischaemia-tolerant mesenchymal
stem cell infusion resulted in significant alterations
in several inflammatory cells, “supporting the
immunomodulatory and anti-inflammatory
mechanisms of ischaemia-tolerant mesenchymal
stem cells,” noted Dr Butler.
Dr Butler concluded, “To our knowledge, this trial
represents the first experience with intravenously
administered ischaemia-tolerant mesenchymal
stem cells in patients with any type of chronic
cardiomyopathy. Further studies should explore the
efficacy of serial dosing to produce more sustained
immunomodulatory effects and thereby perhaps
facilitate improvement in left ventricular structure
and function, and in clinical outcomes.”
PRACTICEUPDATE CARDIOLOGY
EUROPEAN SOCIETY OF CARDIOLOGY CONGRESS
20