CLINICAL
NEWS
American College of Cardiology Extended Learning
12-month follow-up. A recovery index (for patients
with more than 1-year follow-up) was created to
evaluate CCSAC over time. Almost all patients
presented progressive improvement in CCSAC
beginning at 3 months post-procedure (p = 0.002),
which was sustained at 12-month follow-up
(p = 0.002), as well as objective myocardium ischemic area reduction at 6 months (decrease of 15%;
p < 0.024) and 12 months (decrease of 100%;
p < 0.004). QOL per SF-36 questionnaire improved significantly in almost all domains.
Cost-effectiveness analysis showed decreases in
angina-related direct costs. Refractory angina patients presented a sustained long-term improvement
in CCSAC and myocardium ischemic areas after the
procedure. Thus, the authors concluded: “Promonocytes may play a key role in myocardial neoangiogenesis. ReACT dramatically decreased direct costs.”
TISSUE ENGINEERING
One of the limitations of current approaches to
stem cell therapy is the short retention time (days
to maybe a few weeks). It is only during this time
that cells remain in the target tissue after transplantation. A great deal of progress has been made
in the field of tissue engineering to design new
methods to increase cell retention. These include
what Dr. Miller calls “remarkable work” on the
development of scaffolds using both natural and
synthetic materials, including
extracellular matrix to hold
To listen to the
interview with Leslie
either stem cells or genes for
W. Miller, MD, visit
slow and programmed release.
the CSWN YouTube
In addition, scaffolds are being
channel or scan
the QR. Interview
developed with cells implanted
conducted by Peter
for delivery to the target tissue.
A. McCullough, MD.
One of the most exciting
approaches to tissue engineering is the concept of organogenesis or creation of whole
organs that might potentially
be used for elective, off-theshelf transplantation. Research
in this area has demonstrated both the complexity
of individual tissues and cells within each organ,
the challenging requirements of creating equipment to sustain and test these constructs, as well as
which cell to use given the astounding plasticity of
transplanted cells.
According to Dr. Miller and colleagues, in the
introduction to their new book, “We believe we are
on the threshold of a new era of regenerative medicine taking advantage of the lessons learned in the
past decade and the strategies moving into clinical
trials.” ■
REFERENCES:
1. Perin EC, Miller LW, Taylor D, Willerson JT. Stem Cell
and Gene Therapy for Cardiovascular Disease. 1st edition.
Waltham, MA: Academic Press, 2015. ISBN: 9780128018880.
2. Perin EC, Borow KM, Silva GV, et al. Circ Res.
2015;117:576-84.
3. Hossne NA, Cruz E, Buffolo E, et al. Cell Transplant.
2015;24:955-70.
20 CardioSource WorldNews
Lipid Therapy 2016: The ‘Doughnut’ Hole and
PCSK9 Sticker Shock
W
e have recent cholesterol guidelines,1
multiple studies confirming that the
guidelines got it right (putting to rest
much of the original criticism), and new agents recently approved that can dramatically lower LDL-C
levels in patients, including those already on statin
therapy. Thus, nothing left to discuss here, right?
Well, not so fast: there are still a few issues.
THE DOUGHNUT HOLE
C. Noel Bairey Merz, MD, director of the Barbra
Streisand Women’s Heart Center and director of
the Preventive Cardiac Center at Cedars-Sinai Heart
Institute, Los Angeles, CA, recently addressed the
doughnut hole in the guidelines. As a member of
the expert panel, she said they were charged by the
National Heart, Lung, and Blood Institute to develop new cholesterol guidelines an d told to evaluate only higher-quality randomized controlled trial
(RCT) data. No need to reiterate the value of RCT
data here, but that leaves a narrow field of data that
misses huge swaths of the population.
Let’s face it, there is limited generalizability
of the available data for the unstudied, including
those younger than age 40 or older than age 75.
For example, in these two broad age groups, there
is wholly underpowered subgroup data in women
and non-whites, limiting guidelines for these dominant groups. (Women comprise a total of 52% of
the population, while non-white individuals are
projected to make up more than half of the population by 2020.)
Sure, there have been subgroup analyses, but
Dr. Bairey Merz is pointing to the challenge of
making clinical decisions based on limited data
from studies of inadequate sample size, low event
rates, and limited trial durations, thus limiting precision, accuracy, and relevance of trial subgroup
analyses. Consensus is that subgroups should be
treated according to trial evidence of risk and
benefit until proven otherwise.
Having acknowledged that, Dr. Bairey Merz
asked: Can the guidelines be based only on clinical
trials?
• How confident are we that statins do not save
lives in subgroups (age, sex, ethnicity)?
• What do we value? For example, is reduction in
revascularization and angina hospitalization—
which both impact morbidity and cost—provide
justification for the use of statins for primary
prevention?
January 2016