The
information in this column is intended for informational
purposes only, and does not constitute medical advice or
recommendations by the author. Please consult with your
physician
before making any lifestyle or medication changes, or if you have any
other concerns regarding your health.
THROMBUS
(CLOT) ASPIRATION FROM THE CORONARY ARTERIES
Increasingly,
patients with blocked arteries in their hearts are undergoing
percutaneous transluminal coronary angioplasty, or PTCA, instead of the
more invasive coronary artery bypass graft (CABG) surgery that was
previously the only option before PTCA was developed.
When the coronary arteries become severely narrowed or obstructed with
plaque and tiny blood clots, precious oxygen can no longer be delivered
to the heart’s muscle, resulting in severe chest pain (angina) or heart
attack (myocardial infarction).
In many
cases, cardiologists can thread a special balloon-tipped catheter into
a vein in the groin or arm, and use this balloon catheter to open up
narrowed coronary arteries.
After the
artery is reopened, a tiny expandable metal tube (coronary artery
stent) is then usually placed across the narrowed area of the artery in
order to prevent rapid re-narrowing of the same coronary artery again.
However, in many cases, when the balloon is expanded within the
narrowed coronary artery, little chunks of fatty plaque and clotted
blood (thrombus) are dislodged.
These
little bits of solid material can then flow downstream (embolization)
within the coronary arteries, causing additional blockages of the
smaller downstream coronary artery branches.
In a landmark clinical research trial, just published in the New England Journal of Medicine,
researchers added an additional procedure to PTCA.
In addition to using the balloon to re-expand narrowed coronary
arteries, and placing stents within the re-expanded arteries,
researchers actually used specialized, tiny catheters to suck out the
debris that broke away from the coronary arteries undergoing
angioplasty.
A
total of 1,071 volunteers undergoing PTCA for critical narrowing of
their coronary arteries were randomized to either conventional PTCA or
PTCA plus “thrombus aspiration.”
(Smaller
previous studies have suggested that thrombus aspiration, when added to
PTCA, might improve restoration of blood flow to compromised heart
muscle following PTCA.)
This relatively large study appears to have confirmed the clinically
beneficial effects of routine thrombus aspiration.
Compared to patients who received standard PTCA therapy alone, the
patients who additionally underwent thrombus aspiration were
significantly less likely to have angiographic signs of continued poor
blood flow to the affected heart muscle (26% vs. 17%, respectively) and
abnormal EKG changes following PTCA (57% vs. 44%, respectively).
Even more important was the finding that 30-day survival was
significantly better, and complications were significantly fewer, in
patients who achieved the greatest restoration of cardiac blood flow to
the heart after PTCA.
Death within 30 days
of PTCA occurred in 5% of patients with no significant restoration of
blood flow to their hearts, but only 1% of patients died during the
same interval with when PTCA resulted in substantial restoration of
cardiac blood flow.
This
well-designed and well-executed prospective, randomized clinical
research trial strongly suggests, as prior smaller studies have, that a
significant number of patients undergoing PTCA could benefit from the
addition of thrombus aspiration as a routine part of the minimally
invasive management of acute heart attacks and severe angina.
The study’s authors believe that the majority of patients undergoing
PTCA are candidates for thrombus aspiration, suggesting that thrombus
aspiration should now probably become “standard of care” for patients
undergoing PTCA for blocked or severely narrowed coronary arteries.
INTENSIVE
MANAGEMENT OF DIABETES & DEATH
Much
of the diabetes research world has been shaken by the preliminary
findings of a recently aborted clinical research trial that found a
greater risk of death (mostly due to heart attacks) in diabetic
patients who underwent ultra-intensive management of their blood sugar
levels. This large
national diabetes study, which was sponsored bythe
National Heart, Lung and Blood Institute, and which was recently andprematurely
halted, emphasized aggressive lowering of blood sugar levels, which
virtually all diabetes researchers expected would result in fewer
deaths due to known diabetes-related complications, including heart
attacks. The
completely unexpected finding
that the patients who were most aggressively treated to reduce elevated
blood sugar levels actually had a higher
likelihood of dying than patients undergoing less rigorous blood
glucose control has rocked the diabetes research community.
Although an explanation for this counterintuitive result has not yet
been found, this finding has challenged seminal research findings and
decades-old assumptions that stringently reducing elevated blood sugar
levels should improve survival in
diabetics (some
researchers have speculated that the multiple drugs used to achieve
improved blood glucose levels in this controversial research study may
have caused interactions that caused the unexpected deaths, although
this is little more than an educated guess at this point). Now, yet another new
diabetes clinical research study, also published in the New
England Journal of Medicine,
has just reported its results, and these results are more in keeping
with what one would expect from rigid, aggressive control of blood
sugar levels in diabetics.
This
relatively small study, involving only 160 diabetic patients, all of
whom had laboratory evidence of early kidney damage from their
diabetes, were included in this research study.
The patients were randomly divided into two groups.
The “control group” received standard medical therapy for their
diabetes and diabetes-related conditions.
The “experimental group” received intensive therapy that included
aggressive reduction of their blood sugar levels, heart-protective high
blood pressure medications (renin-angiotensin inhibitors), aspirin, and
cholesterol-lowering drugs.
The average
duration of treatment in these two groups of patients was nearly 8
years, and they were then subsequently followed for an average of
almost 6 additional years.
The
results of this long-term study were strikingly different from the
previous study mentioned above.
Intensive management of diabetic patients, in this study, was
associated with a whopping 46% reduction in the risk of death from any
cause, and a 57% reduction in the risk of death due, specifically, to
cardiovascular causes (including heart attacks).
Similarly, progression of kidney disease was significantly lower in the
group receiving intensive management, when compared to the control
group receiving only standard medical treatment.
Finally, the risk of diabetes-associated retinal disease, which is the
most common cause of blindness in our society, was reduced by 55% among
the intensively managed patients.
The
results of this study are exactly what one would have expected from a
more rigorous management of diabetes and diabetes-associated illnesses.
It will now fall to the diabetes experts to look at these two pivotal
studies, and previous studies, in an effort to explain the surprising
and disturbing results of the recently aborted the National Heart, Lung
and Blood Institute study.
Despite the
controversial findings of the National Heart, Lung and Blood Institute
study, my recommendation to all patients with diabetes is that you
should notmake
any changes in your current diabetes treatment plan without first
discussing your concerns with your physician.
For now, anyway, most diabetes experts are not recommending any major
changes in our current approach to managing diabetes.
CURE
FOR DOWN’S SYNDROME?
Down’s
syndrome, or trisomy 21, results when an extra copy of chromosome #21
is inherited, leaving affected individuals with three copies of this
gene instead of the normal two copies.
Down’s syndrome occurs in approximately 1 out of every 800 births,
resulting in approximately 5,000 new cases in the United States each
year, and becomes more common with increasing maternal age at the time
of conception.
Generally, in addition to
the characteristic physical appearance associated with this genetic
abnormality, mild-to-severe mental retardation, congenital heart
disease, Alzheimer’s disease, hearing problems, and a predisposition to
certain cancers, among other conditions, are strongly associated with
Down’s syndrome.
New
research recently presented at the annual Society for Maternal –Fetal
Medicine meeting, and reported by Medpage
Today,
suggests the possibility that the severe learning deficits associated
with Down’s syndrome might actually be reversible, at least in mice
bred with three copies of Chromosome #21.
This
study, which was sponsored by the National Institutes of Health,
treated a group of trisomy 21 mice with the “neuron-protective”
proteins NAP and SAL, and then subjected these mice, as well as
untreated trisomy 21 mice and mice without trisomy 21, to standardized
rodent learning tests.
Following 9 days of
treatment with NAP and SAL, trisomy 21 mice were then subjected to a
water maze learning tests, along with the other two groups of mice.
Incredibly, the NAP- and SAL-treated trisomy 21 mice were able to learn
how to navigate the water maze as easily as the mice without trisomy
21, while the trisomy 21 mice that did not receive the
neuron-protective peptides learned to navigate the maze much more
slowly than either of the other two groups of mice.
While,
as I have emphasized in previous columns, treatments that work in mice
and rats do not always have the same effects in humans, this research
is, nonetheless, dramatic, and offers at least the possibility that
some—or perhaps all—of the severe cognitive disabilities associated
with Down’s syndrome might actually be reversible, something never
thought to be possible before.
It
is estimated that 90-95% of couples who learn that their unborn child
has Down’s syndrome, though prenatal testing, choose not to continue
with the pregnancy.
Perhaps, if the results
of this trisomy 21 mouse research study can be confirmed in humans with
Down’s syndrome, both those living with Down’s syndrome and fetuses
with trisomy 21 might actually someday have the heretofore impossible
opportunity of living without the serious and often disabling cognitive
deficits caused by this genetic illness.