Comment
However, we suspect that this is probably representative With trials of this magnitude costing tens of millions of
of real world practice.
So what is the clinician to learn from this trial that
might have an impact on practice? If a patient is a good
surgical candidate, CABG should remain the mainstay of
treatment. Although survival is the same, the incidence
of clinically apparent myocardial infarction and need
for repeat revascularisation and recurrence of angina is
higher with PCI. In patients who are not good surgical
candidates, PCI is a reasonable alternative to CABG, albeit
with a higher incidence of subsequent clinical events.
So is this the final answer? Probably not, as additional
questions are likely to be raised as new analyses are
performed. All patients in NOBLE will be followed up at
5 years and 10 years, which will add additional valuable
information. Furthermore, with the results of the EXCEL
Trial imminent, further light (or confusion) might be
shed on the issue of disease management.
Should the revascularisation guidelines change on the
basis of the results of this trial? In the ACC/AHA and ESC
Guidelines, CABG is a COR/LOE I B recommendation for
left main revascularisation and PCI is either a I B, IIa B,
or III B recommendation based on Syntax score tertile.5,6
This trial will add to the level of evidence but is not
sufficient by itself to change present guidelines.
Finally, can we expect further trials of comparative
effectiveness between the two treatment strategies?
Ménière’s disease: damaged hearing but reduced vertigo
Published Online Current thinking is that Ménière’s disease (or, more
November 16, 2016
http://dx.doi.org/10.1016/
accurately, Ménière’s syndrome) is a phenotype of
S0140-6736(16)32166-3 unstable or erratic inner ear hearing and vestibular
See Articles page 2753 function that arises from failure of one or more of the
many inner ear homoeostatic systems that regulate
endolymph and perilymph, afferent and efferent nerve
signalling, and blood flow.1 Clinically, the fluctuating
and progressive sensorineural hearing loss tends to
be relatively resistant to treatment (ie, progressive),
but the episodic vertigo is usually quite responsive
to treatment. The combination of diet and lifestyle
adjustments to avoid stressing fragile homoeostatic
systems plus diuretic medication to aid with inner ear
ionic gradient management can control or eliminate
Ménière’s vertigo attacks in over 90% of patients.2
However, a troublesome group remains: 5–10% of all
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US dollars and none underway to our knowledge, it is
probable that these two trials will serve as the evidence
base for management of patients with left main disease
for the foreseeable future.
*Michael Mack, David R Holmes
Baylor Scott & White Health, 3110 Allied Drive, Plano, TX 75093,
USA (MM); Mayo Clinic, Rochester, MN, USA
michael.mack@bswhealth.org
We declare no competing interests.
1 Morice MC, Serruys PW, Kappetein, AP, et al, Five-year outcomes in
patients with left main disease treated with either percutaneous coronary
intervention or coronary artery bypass grafting in the SYNTAX trial
circulation. Circulation 2014; 129: 2388–94.
2 Buszman PE, Buszman PP, Banasiewicz-Szkróbka I, et al. Left main stenting
in comparison with surgical revascularization 10-year outcomes of the
(Left Main Coronary Artery Stenting) LE MANS trial. J Am Coll Cardiol Intv
2016; 9: 318–32.
3 Ahn JM, Roh JH, Kim YH, et al. Randomized trial of stents versus bypass
surgery for left main coronary artery disease: 5-year outcomes of the
PRECOMBAT study. J Am Coll Cardiol 2015; 65: 2198–206.
4 Mäkikallio T, Holm NR, Lindsay M, et al Percutaneous coronary angioplasty
versus coronary artery bypass grafting in treatment of unprotected left
main stenosis (NOBLE): a prospective, randomised, open-label, non-
inferiority trial. Lancet 2016; published online Oct 31. http://dx.doi.
org/10.1016/S0140-6736(16)32052-9.
5 Fihn SD, Blankenship JC, Alexander KP, et al. 2014 ACC/AHA/AATS/
PCNA/SCAI/STS focused update of the guideline for the diagnosis and
management of patients with stable ischemic heart disease.
J Am Coll Cardiol 2014; 64: 1929–49.
6 Windecker S, Kolh P, Alfonso F, et al. 2014 ESC/EACTS Guidelines on
myocardial revascularization. Eur Heart J 2014; 35: 2541–619.
patients with Ménière’s disease are not responsive to
these conservative and medical interventions and need
more aggressive treatment. Nowadays, this most often
means intratympanic drug treatment.
In The Lancet, Mitesh Patel and colleagues3 present
results of a double-blind comparative effectiveness trial
of intratympanic methylprednisolone (n=30) versus
intratympanic gentamicin (n=30) on intractable vertigo
attacks in patients with unilateral Ménière’s disease.
The two treatments were equally effective at reducing
vertigo attacks; the mean number of vertigo attacks in
the final 6 months compared with the 6 months before
the first injection (primary outcome) decreased from 19·9
(SD 16·7) to 2·5 (5·8; 87% reduction) in the gentamicin
group and from 16·4 (12·5) to 1·6 (3·4; 90% reduction)
in the methylprednisolone group (difference –0·9,
www.thelancet.com Vol 388 December 3, 2016

95% CI –3·4 to 1·6). Secondary outcomes related to
other vestibular symptoms and hearing loss (all p>0·05)
were also similar between groups, as was the occurrence
of adverse events (three in each group). Intratympanic
corticosteroid treatment for Ménière’s disease is based on
the supposition that Ménière’s disease symptoms arise
from an inflammatory or other reversible mechanism
that could be favourably altered by administration of
corticosteroid. Tens or hundreds of inner ear proteins have
steroid-binding capability. In fact, it would be startling if
administration of corticosteroid to the inner ear didn’t
have an effect of some kind. But what is the likelihood that
application of such a so-called blunt instrument would do
more good than harm? We have learned empirically over
the past 30 years that intratympanic corticosteroid is safe,
producing few side-effects and virtually no hearing loss
or vestibular damage. It won’t hurt and it might help, so
it has become a popular treatment despite the absence of
strong evidence of efficacy.
By contrast, gentamicin is a hair cell ototoxin. It is
preferentially vestibulotoxic, typically causing much
more vestibular than auditory damage. Administration
of intratympanic gentamicin to patients with Ménière’s
disease is based on the notion that the patient’s vestibular
symptoms are due to the damaged and distorted
vestibular signals emanating from their damaged
ear and that they are better off with no signal than
with a damaged and distorted signal. The objective of
intratympanic gentamicin is to weaken vestibular signals
in the Ménière’s ear to the point at which they are no
longer strong enough to generate a vertigo attack. This
objective is achieved in about 90% of treated patients.
However, there is a price to pay in the form of 1–2 months
of, and possibly permanent, disequilibrium and about
20% risk of further hearing loss in the treated ear.
Patel and colleagues’ study,3 by adhering to stringent
methods, offers robust evidence that both of these
treatments have substantial efficacy, with each achieving
about 90% reduction of vertigo attacks. There was no
placebo control group to provide greater certainty that the
treatment effects were not just the natural course of this
relapsing–remitting disease. However, the data showed a
dramatic drop in vertigo frequency soon after treatment
and no reactivation over 24 months of follow-up, which
is persuasive evidence of a true treatment effect. One
treatment aims to modulate an underlying, and unknown,
disease process and the other treatment is ablative, aiming
www.thelancet.com Vol 388 December 3, 2016
Comment
James Cavallini/Science Photo Library
to weaken or eliminate abnormal function in the damaged
ear. The equivalence of outcome of these two treatments
has shed no new light on the underlying mechanisms
of Ménière’s disease, but will still have important clinical
impact. Since we now know that either intratympanic
corticosteroid or intratympanic gentamicin can be used
to achieve vertigo control, the actual decision of which
to use will be based on doctor and patient consideration
of auditory and vestibular side-effects, status of the
contralateral ear, general health factors, and patient
preference. Although most patients with Ménière’s disease
gradually go deaf in their affected ear, the best news for
patients is that some combination of diet and lifestyle
adjustments, diuretics, and intratympanic drug treatment
can control or eliminate vertigo in 99% of cases. And
there is always the surgical option of labyrinthectomy for
patients who do not respond to intratympanic gentamicin.
Steven D Rauch
Department of Otolaryngology, Massachusetts Eye and Ear
Infirmary, Harvard Medical School, Boston, MA 02114, USA
steven_rauch@meei.harvard.edu
I declare no competing interests.
Copyright © The Author(s). Published by Elsevier Ltd. This is an Open Access
article under the CC BY-NC-ND license.
1 Merchant SN, Adams JC, Nadol JB Jr. Pathophysiology of Meniere’s
syndrome: are symptoms caused by endolymphatic hydrops? Otol Neurotol
2005; 26: 74–81.
2 Rauch SD. Clinical hints and precipitating factors in patients suffering from
Meniere’s disease. Otolaryngol Clin N Am 2010; 43: 1011–17.
3 Patel M, Agarwal K, Arshad Q, et al. Intratympanic methylprednisolone versus
gentamicin in patients with unilateral Ménière’s disease: a randomised,
double-blind, comparative effectiveness trial. Lancet 2016; published online
Nov 16. http://dx.doi.org/10.1016/S0140-6736(16)31461-1.
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