Comment

Management of acute coronary syndrome in the very elderly

www.thelancet.com Vol 387 March 12, 2016

or older. The ndings impressively support the invasive

strategy, with the mean time to coronary angiography
being 3 days after presentation. The primary composite
outcome of myocardial infarction, need for urgent
revascularisation, stroke, and death, was substantially
lower in the invasive group at median follow-up of
153 years (occurring in 93 [406%] of 229 patients
vs 140 [614%] of 228 patients; hazard ratio [HR]
053, 95% CI 041069; number needed to treat 48,
3485). This outcome was driven by reductions in
myocardial infarction (HR 052, 035076) and urgent
revascularisation (019, 007052). The absence of
mortality benet in the invasive group, consistent with
previous studies, might be representative of study size
or observations from other reports that most deaths
after contemporary percutaneous coronary intervention
have non-cardiovascular causes.12
Patients in After Eighty11 had high-risk characteristics
at enrolment, including high prevalence of raised
troponin and comorbid disorders, mean glomerular
ltration rates of 5254 mL/min, and near equal sex
distribution. However, by design the participants
were required to be clinically stable with no
persisting ischaemia before randomisation. Although
4187 octogenarians presented with NSTEMI or unstable
angina, only 457 were actually enrolled because patients
were excluded because of logistical diculties, refusal
to participate, or meeting exclusion criteria such as
poor study protocol compliance, life expectancy of less

Published Online
January 12, 2016
http://dx.doi.org/10.1016/
S0140-6736(16)00036-2
See Articles page 1057

AFP

The very elderly, those aged 80 years or older, constitute

a rapidly increasing subgroup of patients presenting with
ischaemic heart disease.1 Non-ST-elevation (NSTE)-acute
coronary syndrome is the most common manifestation
of acute ischaemic heart disease in the very elderly,
with advanced age conferring higher risks of mortality,
recurrent ischaemia, and readmission to hospital.13
Present guidelines recommend a routine invasive strategy
for the management of NSTE-acute coronary syndrome
in patients at high risk of recurrent events.4 These
recommendations do not distinguish older from younger
patients, despite the scarcity of evidence from randomised
controlled trials for patients aged 80 years or older.4
Management of NSTE-acute coronary syndrome
has many challenges in very elderly patients, who
often present later, have atypical symptoms, and
are a more heterogeneous cohort than younger
patients. These patients are also more likely to have
comorbidities, cognitive decline, physical frailty,
polypharmacy, and more complex coronary artery
disease with greater ischaemic burden.1 These factors
could be perceived to diminish the benets and increase
the risk of complications from invasive treatment.
Consequently the management of very elderly
patients has traditionally been more conservative than
guidelines recommend, with suboptimum access to
early angiography and optimum revascularisation and
medical treatment.5
This underservicing poses a risktreatment paradox.
Evidence from registries of octogenarians6,7 and further
analysis of trials with under-representation of patients
older than 65 years3,8,9 suggest that the very elderly might
derive greater benet from a routine invasive strategy
than younger patients. The only randomised controlled
trial previously dedicated to comparing routine versus
selective invasive management of NSTE-acute coronary
syndrome in very elderly patients was underpowered and
did not lend support to an overall benet, although fewer
clinical events were recorded in participants with baseline
troponin elevation.10
In The Lancet, Nicolai Tegn and colleagues11 report
the results of the open-label After Eighty study, which
compared early invasive and conservative approaches to
management of NSTE-myocardial infarction (NSTEMI)
and unstable angina pectoris in patients aged 80 years

1029

Comment

than 1 year, clinical instability, and continuing or recent

bleeding. These issues, resulting in a small proportion of
eligible participants, emphasise the diculties of trials
with a very elderly population, but also suggest that the
results might not be applicable to most octogenarians
with NSTEMI or unstable angina.
Revascularisation rates approached 50% in the
invasive group and only 4% in the conservative group.
The low rate of percutaneous coronary intervention
in the conservative group is consistent with the need
for clinical stability at time of enrolment and is much
lower than in other studies.3,8,10 Use of evidence-based
drugs was high in both groups and dropout rates low.
These factors and predominant enrolment of troponinpositive NSTEMI would have promoted the substantial
treatment benet in the invasive group. The clinical
event rates continued to diverge until at least 1 year of
follow-up, with no subgroup dierences apart from an
attenuated treatment eect with increasing age and
no signicant benet in the small numbers of patients
older than 90 years.
After Eighty11 reassures us that invasive management
of NSTEMI or unstable angina can be done in clinically
stable octogenarians without compromising patient
safety. Contrast-induced nephropathy and major
bleeding events were much less frequent in the invasive
group than in previous studies. The lower frequency of
these adverse events happened despite high usage of
dual antiplatelet treatment, use of oral anticoagulation
for concomitant atrial brillation, and a relatively high
prevalence of renal dysfunction. The predominant use
of radial artery access, the absence of glycoprotein IIb or
IIIa inhibitor use, and the careful nature of the exclusion
criteria would all have contributed to the acceptable
bleeding rates.
The After Eighty study11 provides the most compelling
evidence so far validating existing guidelines for
routine invasive management of NSTEMI or unstable
angina in the very elderly. Its results underline some
of the strengths of contemporary best-practice
management, but still remind us that decision making
in elderly patients has to be individually tailored,
considering life expectancy, comorbid illnesses,
bleeding risk, cognitive and functional status, and
patient preference. Further analysis should address
the eect of invasive management on quality-of-life
measures, readmission to hospital, and health-care
1030

costs. However, other studies will need to address

whether invasive management of NSTE-acute coronary
syndrome in the very elderly should involve complete
or culprit lesion-only revascularisation, and use of
new antiplatelet and high-dose statins. Finally, as we
redene age limits for invasive management, whether
this should extend to nonagenarians as well remains to
be seen.
*Peter J Psaltis, Stephen J Nicholls
School of Medicine, University of Adelaide, Adelaide, SA, Australia;
and Vascular Research Centre, Heart Health Theme,
South Australian Health and Medical Research Institute, Adelaide,
SA 5000, Australia
peter.psaltis@sahmri.com
SJN has received research funding from AstraZeneca, Amgen, Cerenis, Eli Lilly,
The Medicines Company, Resverlogix, Novartis, InfraReDx; personal fees from
Boehringer Ingelheim, CSL Behrin, and Merck; and research funding and
personal fees from Sano-Regeneron. PJP declares no competing interests.
1

10

11

12

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