Laser heart surgery - dead on the vine?
By DrRich
Medical science is actively exploring several new methods
of treating coronary artery disease. Of
these new therapies, one of the most promising has been direct myocardial
revascularization (DMR). DMR
uses a special laser tool to “drill” tiny holes into portions of heart
muscle that are not getting sufficient blood flow (due to blockages in the
coronary arteries supplying that muscle). These
tiny holes, in theory, provide an alternate means of getting blood to the
blood-starved muscle.
But now, results from a large, randomized clinical trial -
reported in October, 2000 - appear to have placed a major roadblock in DMR’s clinical
acceptance.
How is DMR done?
There are two major types of DMR: surgical DMR, and
transcatheter DMR.
Surgical DMR has been an FDA-approved technique for several
years. Surgical DMR is performed by
cardiac surgeons in the operating room. A
chest incision is made, the heart is exposed, the affected portion of heart
muscle (i.e., the part of the heart muscle that is not getting sufficient blood
flow) is identified visually, and the DMR laser tool is used to bore a series of
tiny holes through that part of the muscle and into the cardiac chamber.
Transcatheter DMR, in contrast, is performed in the
catheterization laboratory by cardiologists. In the transcatheter procedure
(which is still investigational and thus is not FDA-approved) a special catheter
is inserted into the heart through a blood vessel (exactly as is done in a
standard heart catheterization). Using
a high-tech mapping system to identify the affected portion of heart muscle, a
series of laser holes are made into that affected portion, directly from inside
the heart.
How is DMR supposed to work?
Leaving aside for the moment the question of whether DMR
works at all, the most straightforward theory of how this procedure improves the
heart is simply this: The new holes “drilled” into the heart muscle provide
channels for the diffusion of blood directly into the blood-starved cardiac
muscle.
What were the early clinical results?
Almost universally, early reports indicated that DMR
significantly improved symptoms in many patients with severe coronary artery
disease.
The usage of DMR has always been limited to patients who,
in essence, had no other medical options. It
has been offered only to patients whose coronary artery disease was so severe
that they were deemed not to be candidates for bypass surgery, angioplasty or
stents, and their maximal drug therapy had proved insufficient for relieving
their symptoms.
In using DMR to treat these difficult-to-manage patients,
early results seemed extremely promising. Investigators
reported (in medical meetings and in journals) many success stories, in which
patients with refractory angina were remarkably improved after the procedure.
Based on such early results, the FDA was moved to approve the surgical
DMR tools for limited use in highly selected patients.
And biotech companies began to invest millions of dollars in developing
the technology for delivering DMR therapy more cheaply, conveniently, and
presumably safely, in the catheterization laboratory.
Three such transcatheter DMR systems are now undergoing
clinical investigation. In earlier
randomized trials that compared transcatheter DMR to standard medical therapy
(that is, trials without a placebo group), DMR as usual seemed to result in
improved exercise tolerance and less angina.
The large randomized trial finally reported last week –
DIRECT (the DMR in Regeneration of Endomyocardial Channels Trial) – was
supposed to provide final proof of the effectiveness and safety of DMR.
Its results have been anxiously awaited.
How was the DIRECT study conducted?
298 patients with severe coronary artery disease were
entered into DIRECT. These patients
were divided randomly into two groups. One
group had the transcatheter DMR procedure performed.
The other group had an identical catheterization, but instead of
receiving DMR they received a “placebo” procedure in which the medical
personnel went through the motions of delivering DMR, but in fact no laser holes
were applied. Patients enrolled in DIRECT were “blinded” – they did
not know whether they had actually received the actual DMR, or merely the
placebo procedure.
Patients were then tested 6 months after the procedure to
see whether their exercise tolerance and symptoms of angina had improved.
What did DIRECT show?
The widely anticipated results of DIRECT were presented
last week at the Transcatheter Cardiovascular Therapeutics 2000 conference.
As everybody expected, patients who actually received DMR
had a significant improvement both in exercise tolerance and in anginal symptoms
at a follow-up interval of 6 months, duplicating the results of earlier
non-placebo-controlled studies.
However, much to everyone’s amazement, the patients
receiving the placebo procedure had an equally significant improvement in
exercise tolerance, angina improvement, and in all other objective assessment
tools used in this trial.
What do the results of DIRECT mean?
These results indicate two things.
First, transcatheter DMR, despite prior trials to the
contrary, simply does not work. Absolutely
no benefit over the placebo procedure – not even a hint of benefit – was
seen.
Second, the placebo procedure in DIRECT resulted in an
impressive placebo response, once again demonstrating the importance of using
placebo controls – whenever possible – in clinical trials.
What does the improvement in the placebo group mean?
The results of DIRECT illustrate, extremely graphically,
the reality of the “placebo effect.” It
seems quite clear that the placebo effect can be far more than a mere
psychological response to an ineffective treatment. Indeed, it appears to represent a true physiological
phenomenon. The patient not only thinks
there has been an improvement, there often appears to be a real improvement.
What causes the placebo effect is unknown.
This phenomenon does, however, fit the growing perception within the
medical profession that the mind has subtle, poorly understood, but important
effects over the body.
As a general rule, it appears that the more desperate the
patient, the more likely a novel treatment is to generate a placebo effect.
Certainly the patients eligible for DIRECT had every right to feel
desperate about their heart disease, and this may explain the magnitude of the
placebo response observed in DIRECT.
To the extent that the placebo effect sooths a suffering
individual’s despair – whether psychologically or physiologically –
that’s good. (Indeed,
until the mid 20th century, much of what a doctor had to offer
his/her patients was most likely a placebo effect from various poultices and
other ministrations.) But to
the extent that the placebo response confounds our ability to assess the
effectiveness of a new therapy – especially when that new therapy is expensive
or potentially risky (characterizations that apply to DMR) – that’s bad.
The placebo response is what makes it so difficult to assess claims made for various medical treatments – either treatments used in traditional medicine, or by practitioners of alternative medicine – that have not been subjected to randomized trials in comparison with placebo. Many of the case reports (in traditional medicine) and testimonials (in alternative medicine) touting the benefits of various and sundry therapies could easily be due to a placebo effect, and not to the therapy itself. Without good clinical trials, whether the treatment itself adds any actual therapeutic benefit is not really knowable. The results of DIRECT drive this point home especially forcefully.
What are the implications for DMR?
Now that a large, well-designed, randomized, blinded,
placebo-controlled trial has been conducted testing DMR, we can say with a high
degree of certainty that the supposed benefits seen with DMR for the past
half-decade have actually represented a particularly striking placebo effect.
As stunning and as unexpected as the results of DIRECT are,
the answer seems plain. DMR
doesn’t work. If one wished to achieve the placebo effect seen in
DIRECT, there are cheaper and safer ways to do so.
The real question at this point, it seems, is not whether
DMR is an effective therapy (it’s not); but how will the medical establishment
respond to this clear-cut, scientific refutation of a promising therapy in which
millions of dollars have been invested, and scores of institutional and
individual reputations have been staked? Will the treatment be dropped, as the
data suggest should happen, and the money and intellectual energy be directed
toward more fruitful therapies? Or will those with a vested interest in
the success of DMR persist in finding a way to recoup their investment?
Already rationalizations have been advanced.
DIRECT applies only to transcatheter DMR, some surgeons have said, and
not to the surgical variety of DMR.
There is no reason, of course, to think that surgical DMR
is fundamentally better than transcatheter DMR.
Both procedures drill laser holes into the heart muscle. And the
magnitude of “benefit” from surgical DMR is roughly the same as was found in
DIRECT – that is, it is roughly the same as the placebo effect.
Furthermore, surgical DMR will almost certainly never be subjected to a
placebo-controlled trial, since it is considered highly unethical to perform
“sham” operations (making the surgical incision, but not performing the
actual surgery) for the sake of scientific accuracy.
So if surgeons get away with the claim that DIRECT does not apply to their
form of DMR, that claim will likely never be scientifically refuted.
The medical establishment has been demanding for years that
purveyors of alternative therapies (such as chelation therapy) subject their pet
cures to placebo-controlled trials. The
implied expectation is that if such trials showed no benefit over placebo, then
the advocates of these therapies would (naturally) be compelled to drop their claims, no matter
how invested they were in believing those claims.
What do you think? Enter the Heart Disease Forum:
