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However, we suspect that this is probably representative With trials of this magnitude costing tens of millions of
of real world practice. US dollars and none underway to our knowledge, it is
So what is the clinician to learn from this trial that probable that these two trials will serve as the evidence
might have an impact on practice? If a patient is a good base for management of patients with left main disease
surgical candidate, CABG should remain the mainstay of for the foreseeable future.
treatment. Although survival is the same, the incidence
of clinically apparent myocardial infarction and need *Michael Mack, David R Holmes
for repeat revascularisation and recurrence of angina is Baylor Scott & White Health, 3110 Allied Drive, Plano, TX 75093,
USA (MM); Mayo Clinic, Rochester, MN, USA
higher with PCI. In patients who are not good surgical
candidates, PCI is a reasonable alternative to CABG, albeit
We declare no competing interests.
with a higher incidence of subsequent clinical events.
1 Morice MC, Serruys PW, Kappetein, AP, et al, Five-year outcomes in
So is this the final answer? Probably not, as additional patients with left main disease treated with either percutaneous coronary
intervention or coronary artery bypass grafting in the SYNTAX trial
questions are likely to be raised as new analyses are circulation. Circulation 2014; 129: 2388–94.
performed. All patients in NOBLE will be followed up at 2 Buszman PE, Buszman PP, Banasiewicz-Szkróbka I, et al. Left main stenting
in comparison with surgical revascularization 10-year outcomes of the
5 years and 10 years, which will add additional valuable (Left Main Coronary Artery Stenting) LE MANS trial. J Am Coll Cardiol Intv
2016; 9: 318–32.
information. Furthermore, with the results of the EXCEL
3 Ahn JM, Roh JH, Kim YH, et al. Randomized trial of stents versus bypass
Trial imminent, further light (or confusion) might be surgery for left main coronary artery disease: 5-year outcomes of the
PRECOMBAT study. J Am Coll Cardiol 2015; 65: 2198–206.
shed on the issue of disease management. 4 Mäkikallio T, Holm NR, Lindsay M, et al Percutaneous coronary angioplasty
Should the revascularisation guidelines change on the versus coronary artery bypass grafting in treatment of unprotected left
main stenosis (NOBLE): a prospective, randomised, open-label, non-
basis of the results of this trial? In the ACC/AHA and ESC inferiority trial. Lancet 2016; published online Oct 31. http://dx.doi.
Guidelines, CABG is a COR/LOE I B recommendation for org/10.1016/S0140-6736(16)32052-9.
5 Fihn SD, Blankenship JC, Alexander KP, et al. 2014 ACC/AHA/AATS/
left main revascularisation and PCI is either a I B, IIa B, PCNA/SCAI/STS focused update of the guideline for the diagnosis and
management of patients with stable ischemic heart disease.
or III B recommendation based on Syntax score tertile.5,6 J Am Coll Cardiol 2014; 64: 1929–49.
This trial will add to the level of evidence but is not 6 Windecker S, Kolh P, Alfonso F, et al. 2014 ESC/EACTS Guidelines on
myocardial revascularization. Eur Heart J 2014; 35: 2541–619.
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 patients with Ménière’s disease are not responsive to
November 16, 2016
accurately, Ménière’s syndrome) is a phenotype of these conservative and medical interventions and need
S0140-6736(16)32166-3 unstable or erratic inner ear hearing and vestibular more aggressive treatment. Nowadays, this most often
See Articles page 2753 function that arises from failure of one or more of the means intratympanic drug treatment.
many inner ear homoeostatic systems that regulate In The Lancet, Mitesh Patel and colleagues3 present
endolymph and perilymph, afferent and efferent nerve results of a double-blind comparative effectiveness trial
signalling, and blood flow.1 Clinically, the fluctuating of intratympanic methylprednisolone (n=30) versus
and progressive sensorineural hearing loss tends to intratympanic gentamicin (n=30) on intractable vertigo
be relatively resistant to treatment (ie, progressive), attacks in patients with unilateral Ménière’s disease.
but the episodic vertigo is usually quite responsive The two treatments were equally effective at reducing
to treatment. The combination of diet and lifestyle vertigo attacks; the mean number of vertigo attacks in
adjustments to avoid stressing fragile homoeostatic the final 6 months compared with the 6 months before
systems plus diuretic medication to aid with inner ear the first injection (primary outcome) decreased from 19·9
ionic gradient management can control or eliminate (SD 16·7) to 2·5 (5·8; 87% reduction) in the gentamicin
Ménière’s vertigo attacks in over 90% of patients.2 group and from 16·4 (12·5) to 1·6 (3·4; 90% reduction)
However, a troublesome group remains: 5–10% of all in the methylprednisolone group (difference –0·9,

2716 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

James Cavallini/Science Photo Library

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 to weaken or eliminate abnormal function in the damaged
it has become a popular treatment despite the absence of ear. The equivalence of outcome of these two treatments
strong evidence of efficacy. has shed no new light on the underlying mechanisms
By contrast, gentamicin is a hair cell ototoxin. It is of Ménière’s disease, but will still have important clinical
preferentially vestibulotoxic, typically causing much impact. Since we now know that either intratympanic
more vestibular than auditory damage. Administration corticosteroid or intratympanic gentamicin can be used
of intratympanic gentamicin to patients with Ménière’s to achieve vertigo control, the actual decision of which
disease is based on the notion that the patient’s vestibular to use will be based on doctor and patient consideration
symptoms are due to the damaged and distorted of auditory and vestibular side-effects, status of the
vestibular signals emanating from their damaged contralateral ear, general health factors, and patient
ear and that they are better off with no signal than preference. Although most patients with Ménière’s disease
with a damaged and distorted signal. The objective of gradually go deaf in their affected ear, the best news for
intratympanic gentamicin is to weaken vestibular signals patients is that some combination of diet and lifestyle
in the Ménière’s ear to the point at which they are no adjustments, diuretics, and intratympanic drug treatment
longer strong enough to generate a vertigo attack. This can control or eliminate vertigo in 99% of cases. And
objective is achieved in about 90% of treated patients. there is always the surgical option of labyrinthectomy for
However, there is a price to pay in the form of 1–2 months patients who do not respond to intratympanic gentamicin.
of, and possibly permanent, disequilibrium and about
20% risk of further hearing loss in the treated ear. Steven D Rauch
Patel and colleagues’ study,3 by adhering to stringent Department of Otolaryngology, Massachusetts Eye and Ear
Infirmary, Harvard Medical School, Boston, MA 02114, USA
methods, offers robust evidence that both of these
treatments have substantial efficacy, with each achieving
I declare no competing interests.
about 90% reduction of vertigo attacks. There was no
Copyright © The Author(s). Published by Elsevier Ltd. This is an Open Access
placebo control group to provide greater certainty that the article under the CC BY-NC-ND license.
treatment effects were not just the natural course of this 1 Merchant SN, Adams JC, Nadol JB Jr. Pathophysiology of Meniere’s
syndrome: are symptoms caused by endolymphatic hydrops? Otol Neurotol
relapsing–remitting disease. However, the data showed a 2005; 26: 74–81.
dramatic drop in vertigo frequency soon after treatment 2 Rauch SD. Clinical hints and precipitating factors in patients suffering from
Meniere’s disease. Otolaryngol Clin N Am 2010; 43: 1011–17.
and no reactivation over 24 months of follow-up, which 3 Patel M, Agarwal K, Arshad Q, et al. Intratympanic methylprednisolone versus
is persuasive evidence of a true treatment effect. One gentamicin in patients with unilateral Ménière’s disease: a randomised,
double-blind, comparative effectiveness trial. Lancet 2016; published online
treatment aims to modulate an underlying, and unknown, Nov 16.
disease process and the other treatment is ablative, aiming Vol 388 December 3, 2016 2717