ARTICLES
Articles
Trial of invasive versus medical therapy in elderly patients with
chronic symptomatic coronary-artery disease (TIME):
a randomised trial
The TIME Investigators*
Summary
Background Since previous randomised treatment trials in
coronary disease have focused on patients younger than
75 years of age, their findings might not apply to the
elderly population in whom the cardiac risk profile, risk of
intervention, and comorbidities are increased. We aimed to
assess quality of life and outcome of elderly patients with
coronary disease after medical or revascularisation
therapy.
Methods In this randomised, prospective, multicentre trial,
we enrolled patients aged 75 years or older with chronic
angina of at least Canadian Cardiac Society class II despite
at least two antianginal drugs. Patients were randomly
assigned coronary angiography and revascularisation or
optimised medical therapy. The primary endpoint was
quality of life after 6 months, as assessed by
questionnaire and the presence of major adverse cardiac
events (death, non-fatal myocardial infarction, or hospital
admission for acute coronary syndrome with or without the
need for revascularisation). Analysis was by intention to
treat.
Findings 150 patients were assigned medical therapy and
155 invasive therapy. Two protocol violators in each group
were not included in the analysis. After 6 months, angina
severity decreased and measures of quality of life
increased in both treatment groups; however, these
improvements were significantly greater after
revascularisation. Major adverse cardiac events occurred in
72 (49%) of patients in the medical group and 29 (19%) in
the invasive group (p<0·0001).
Interpretation Patients aged 75 years or older with angina
despite standard drug therapy benefit more from
revascularisation than from optimised medical therapy in
terms of symptom relief and quality of life. Therefore, these
patients should be offered invasive assessment despite
their high risk profile followed by revascularisation if
feasible.
Lancet 2001; 358: 951–957
See Commentary page 945
*Members listed at end of paper
Correspondence to: Prof M Pfisterer, Division of Cardiology,
University Hospital, CH-4031 Basel, Switzerland
(e-mail: pfisterer@email.ch)
THE LANCET • Vol 358 • September 22, 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Introduction
For patients with symptomatic chronic coronary-artery
disease, revascularisation therapy provides symptom
relief, and certain high-risk subsets have improved
survival.1–7 However, since these findings are based on
middle-aged populations, they might not apply to
elderly patients in whom the risk of mortality and
disability from revascularisation procedures is increased
and in whom comorbidity is more prevalent.8,9
Individuals older than 75 years represent the fastest
growing population segment, and more than a third of
health-care expenditures are spent on them. Coronary-
artery disease is the most prominent cause of morbidity
and mortality in this age-group, and rates have not
declined over time as they have in younger
individuals.9–12 Therefore, the question of management
strategies in elderly patients with symptomatic coronary-
artery disease is important for individual patients and for
society, in view of health-care costs.
We did a prospective, randomised, multicentre study
in patients aged 75 years or older with angina pectoris of
class II or more (according to the Canadian Cardiac
Society classification [CCS]) despite treatment with at
least two antianginal drugs. We aimed to compare an
invasive strategy of left-heart catheterisation followed by
either percutaneous coronary intervention (PCI) or
coronary-artery bypass graft (CABG) surgery, with a
strategy of optimised medical therapy.
Patients and methods
Patients
Patients aged 75 years or older who were referred to
participating centres in Switzerland for assessment of
chest pain refractory to at least two antianginal drugs
were included, irrespective of whether or not they had
had previous revascularisation procedures. Exclusion
criteria were: acute myocardial infarction within the
previous 10 days; concomitant valvular or other heart
disease; predominant congestive heart failure; life-
limiting comorbid disease such as cancer, severe renal
failure, &c; unwillingness to undergo revascularisation
or impossibility of revascularisation; and impossibility of
increasing or optimising medical therapy.
The study was approved by the ethics committee of
the Swiss Academy of Medical Sciences and by the local
ethics committee of each centre. Patients gave written
informed consent.
Methods
The study protocol has been described previously.13 In
short, patients were randomised centrally by computer-
generated random-number lists to the “optimum
medical” or “invasive” strategy. The optimum medical
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Invasive strategy Optimum medical

305 enrolled (n=153) strategy (n=148)
Demographics
Mean (SD) age (years) 80·0 (3·7) 79·8 (3·5)
Women 67 (44%) 64 (43%)
150 assigned 155 assigned Risk factors
optimum invasive Hypertension 99 (65%) 86 (58%)
Diabetes 35 (23%) 33 (22%)
medical treatment
Current smoking 56 (37%) 46 (31%)
treatment Hypercholesterolaemia 79 (53%) 65 (44%)
History
Prior infarction 67 (44%) 74 (50%)
1 had MI within 2 had MI within Prior PCI 12 (8%) 12 (8%)
10 days of 10 days of Prior CABG 16 (10%) 17 (11%)
randomisation* randomisation* Comorbidity
1 withdrew Prior congestive heart failure 22 (15%) 20 (14%)
Cerebrovascular accident 16 (11%) 13 (9%)
consent*
4 refused COPD 13 (9%) 10 (7%)
catheterisation Peripheral artery disease 34 (22%) 19 (13%)
1 died Ulcer/liver disease 12 (8%) 9 (6%)
Renal insufficiency 20 (13%) 17 (12%)
1 had cancer Other diseases 43 (29%) 37 (26%)
Mean (SD) mini 26 (2) 27 (2)
mental-state score
148 assessed 147 underwent
Symptoms
for primary catheterisation
Angina CCS class
endpoint 2 28 (18%) 38 (26%)
3 71 (46%) 70 (47%)
4 54 (35%) 40 (27%)
Dyspnoea 87 (57%) 85 (57%)
Mean (SD) vital signs
Pulse rate (bpm) 69 (13) 69 (13)
80 assigned 33 assigned 34 assigned Systolic blood pressure (mm Hg) 137 (23) 137 (22)
Diastolic blood pressure (mm Hg) 76 (13) 77 (12)
PTCA CABG medical
Drug therapy
treatment†
␤-blocker* 124 (82%) 106 (72%)
Calcium antagonist* 77 (51%) 73 (49%)
Long-acting nitrates* 115 (76%) 112 (76%)
5 with no Molsidomine* 60 (40%) 53 (36%)
1 had 3 refused
Potassium blockers* 2 (2%) 9 (6%)
stroke catheter
Diuretics 59 (39%) 56 (38%)
ACE inhibitors 34 (23%) 52 (35%)
Lipid-lowering drugs 37 (25%) 33 (22%)
Aspirin 128 (85%) 122 (82%)
79 received 30 received 43 received Coumadin 18 (12%) 18 (12%)
PTCA CABG medical Heparin 28 (19%) 28 (19%)
treatment Number of antianginal drugs
2 86 (56%) 89 (60%)
3 56 (37%) 47 (32%)
>3 11 (7%) 12 (8%)
Figure 1: Trial profile
Non-invasive test results
MI=myocardial infarction. PTCA=percutaneous transluminal coronary
Mean (SD) LVEF 53 (12) 52 (13)
angioplasty. CABG=coronary-artery bypass grafting.
Ischaemia detection possible 68 (44%) 66 (45%)
*Not included in primary endpoint assessment.
†11 with coronary-artery disease included. Number of diseased vessels on angiography
0 11 (7%) ··
1 20 (14%) ··
strategy was an increase in the number or dose of 2 28 (19%) ··
3 88 (60%) ··
antianginal drugs, with the aim to reduce pain as much
Left main disease† 21 (14%) ··
as possible. Repeated outpatient visits were organised by
the centres or the referring physicians. Additionally, CABG=coronary-artery bypass grafting, CCS=Canadian Cardiac Society,
COPD=chronic obstructive pulmonary disease, ACE=angiotensin-converting
antiaggregants and lipid-lowering drugs were advised. enzyme, LVEF=left-ventricular ejection fraction, PCI=percutaneous coronary
The invasive strategy involved coronary angiography in intervention. Mini mental-state score on scale from 0 to 30, with lower scores
all patients, followed by PCI or CABG surgery if indicating more cognitive impairment. *Antianginal drugs. †Counted in patients
with two or three diseased vessels.
feasible, according to the decision of cardiologists and
Table 1: Baseline characteristics
cardiac surgeons in participating centres. The culprit
lesion had to be identified, if possible, but whether to
attempt full or only culprit-lesion revascularisation was score index (DASI),16 the Rose questionnaire for
left to the discretion of the treating physicians. Thus, angina,17 and questions about education and economic
patients were included on the basis of their clinical status.
presentation, and coronary angiography was done on a Follow-up after 6 months was done in the outpatient
per-protocol basis only in patients in the invasive group. clinic, where symptomatic and vital status was recorded,
After collection of baseline data including a mini and quality of life assessed by the same questionnaire as
mental-state test,14 quality of life was assessed by a at baseline. The primary endpoint of the study was
questionnaire given to the patients for self-completion; defined as quality of life assessed by the questionnaire,
help was allowed if necessary. The questionnaire and by the composite outcome of death, documented
contained questions from SF36,15 the Duke activity non-fatal myocardial infarction, and hospital admission

952 THE LANCET • Vol 358 • September 22, 2001

For personal use. Only reproduce with permission from The Lancet Publishing Group.

Measure of quality Invasive
of life strategy
General health (SF36) 11·4 (20·0) (n=99; p<0·0001)
Bodily pain (SF36) 31·3 (32·2) (n=115; p<0·0001)
Vitality (SF36) 10·6 (20·6) (n=102; p<0·0001)
Duke activity score index 7·2 (14·1) (n=112; p<0·0001)
Rose score –1·9 (2·0) (n=111; p<0·0001)
Angina pectoris class –2·0 (1·3) (n=133; p<0·0001)
Number of anginal medications –1·0 (1·2) (n=132; p<0·0001)
Scores are calculated at the individual level as mean (SD) differences from baseline to 6 month follow-up values. SF36 items scored on a scale from 0 to 100 with
higher scores indicating a more favourable status. Only dimensions with significant changes between treatment groups shown. DASI scored on a scale from 0 to 58
with higher scores indicating a more favourable status. Angina CCS class and Rose score with 4 indicating pain at rest and 0 no pain. *Invasive vs medical. †Invasive
vs medical without revascularisation.
Table 2: Changes in measures of quality of life between baseline and 6-month follow-up assessments
for increasing or unstable angina (acute coronary
syndrome) with or without the need for revasc-
ularisation after 6 months. Myocardial infarction was
defined as a clinical event with significant electro-
cardiographic and enzyme changes and, in context with
revascularisation, as infarct-typical electrocardiographic
changes with increases in concentrations of creatine
kinase MB, troponin, or both, of twice the upper limit of
normal.
Statistical analysis
Data were collected on specially designed case-report
forms and double-entered in a computer file at the data
centre. Quantitative and score variables were
summarised in terms of mean values and SDs, and their
comparison between groups was done with the
Wilcoxon-Mann-Whitney test. For the comparison of
categorical values between groups, Fisher’s exact test
and the ␹2 test were used. Changes in quantitative
variables within groups were assessed with the paired t
test or the signed rank test, which was also used to
assess changes in score variables within groups. Time
variables with censored values were described by
Kaplan-Meier statistics, and comparison between
groups was done with the log-rank test. Quality of life
questionnaires were analysed according to the specific
tests used. Individual scores (SF36 and DASI)
were calculated if not more than 50% of the respective
items were missing. In case of incomplete data,
this calculation was done with appropriate multi-
plication factors (SF36) or by interpreting missing
values as negative responses (DASI). Results were
validated with lower thresholds for the missing rates
in complementary analyses. The primary endpoint
was analysed by intention to treat as a composite
endpoint, and all components separately as secondary
endpoints.
Sample size was estimated on the basis of results of
the ACME trial,5 in which 100 patients in each group
led to a significant result regarding exercise time and
angina severity. We postulated that, to reach
100 patients with revascularisation, we would need
150 patients in the invasive group, because we expected
that the rate of “revascularisation not possible or
refused” in these elderly patients would be about 33%.
This sample size would also allow us to detect a
difference in average changes over time of the order of
0·5 SD between the two experimental groups in SF36
scales and angina scores. A sample size of 154 patients
in each group would allow us to detect a significant
difference in primary endpoint events at a level of 5%
with a power of 80% if they occurred in the optimised
medical and invasive groups at rates of 40% and 25%,
respectively.
THE LANCET • Vol 358 • September 22, 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.
ARTICLES
Optimum medical p* Optimum medical strategy p†
strategy without revascularisation
3·8 (18·7) (n=104; p=0·04) 0·008 –1·1 (17·3)(n=67; p=0·64) <0·0001
23·6 (31·5) (n=114; p<0·0001) 0·12 17·1 (29·1)(n=72; p<0·0001) 0·006
6·1 (22·4) (n=100; p=0·005) 0·16 4·0 (21·9) (n=60; p=0·16) 0·04
5·3 (14·4) (n=107; p=0·0007) 0·17 4·0 (12·1) (n=67; p=0·01) 0·09
–1·1 (1·9) (n=110; p<0·0001) 0·008 –0·8 (1·7) (n=69; p=0·0001) 0·0003
–1·6 (1·4) (n=137; p<0·0001) 0·01 –1·3 (1·2) (n=90; p<0·0001 0·0001
–0·2 (1·2) (n=139; p<0·0001) <0·0001 0·2 (1·0) (n=91; p=0·04) <0·0001
Results
Of 305 patients initially randomised, four were excluded
by the Critical Event Committee because three had the
exclusion criteria of myocardial infarction within
10 days of randomisation, and one withdrew consent
immediately after inclusion (figure 1). These patients
were not included in the intention to treat analysis.
Baseline characteristics are shown in table 1. Study
patients were on average 80·0 years old (SD 3·7), and
almost half were female and had a high coronary risk
profile. More than half had significant comorbid
disorders. Three quarters of the patients presented with
angina higher than CCS class II despite an average of
2·5 antianginal drugs per patient. Left-ventricular
function determined non-invasively was slightly
impaired, and ischaemia could be detected in about half
the patients. There were no significant differences
between the two study groups except for use of
angiotensin-converting-enzyme inhibitors, which was
somewhat higher in patients in the medical group.
Coronary angiograms in patients in the invasive group
showed multivessel disease in 116 (79%) and no
significant coronary-artery stenoses in 11 (7%).
147 (96%) of 153 patients in the invasive group were
catheterised, of whom 109 (74%) underwent
revascularisation (figure 1). The remaining 38 (26%)
were treated medically because they could not be
revascularised (19), because they refused
revascularisation (7), or had no significant coronary-
artery disease (11). 25 patients with CABG surgery
received at least one arterial conduit, and 68 PCI
patients at least one stent. In the optimum medical
group, antianginal medication was increased by a mean
of 0·80 (SD 0·6) drugs per patient, with additional
increases in drug dosages in 81 (55%) patients.
At baseline, there were no differences in symptom
status and quality of life between the two study groups.
The questionnaires could be filled out by the patients
themselves in 157 (52%) at baseline and 220 (73%) at
follow-up; the remaining patients needed assistance. At
follow-up, 244 (81%) patients completed the quality of
life questionnaire. Angina severity decreased, and all
indices of quality of life improved significantly during
follow-up in both groups; the improvements in angina
severity and health status were greater in patients in the
invasive group than in the medical group (table 2). The
improvements with invasive treatment were consistent
throughout seven of the eight dimensions of the SF36
(except for emotional role function) and all other scores
measured. However, only those mentioned above were
significant. Revascularisation during follow-up further
improved these quality of life parameters in patients in
the optimum medical group (data not shown), and
smaller quality of life benefits were measured in patients
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Invasive Optimum p Event-free survival

strategy medical strategy 1·0 Invasive
(n=153) (n=148) Optimum medical
Death 13 6 0·15*
Non-fatal infarctions 12 17 0·46†
0·8

Proportion without MACE

Hospital admissions for ACS
Without revascularisation 5 18 0·006†
With revascularisation 10 55 <0·0001†
Total major adverse 40 96 <0·0001†
0·6
cardiac events
ACS=acute coronary syndrome. *Fisher’s exact test. †Wilcoxon-Mann-Whitney
test.
Table 3: Major adverse cardiac events 0·4 p<0·0001

in the optimum medical group who received medical

therapy alone throughout follow-up (table 2).
During follow-up (mean 184·4 days [SD 14·4]), 0·2
major adverse cardiac events occurred overall in 101
study patients: 29 (19%) in the invasive group and 72
(49%) in the optimum medical group (p<0·0001, 0·0
table 3). This difference was mainly due to higher rates
0 50 100 150 200
of hospital admissions for acute coronary syndrome with
or without the need for revascularisation and for non- Days after inclusion
Number at risk
fatal myocardial infarction in the optimum medical
Invasive group 153 137 128 125 122*
group than in the invasive group. Overall, the 6-month
mortality rate was low (6·3%), but it was twice as high Optimum medical 148 110 90 78 76*
group
in the invasive group as in the optimum medical group,
although this difference was not significant. The higher Time to death and non-fatal
number of deaths in the optimum medical group was myocardial infarction
mainly due to patients who did not undergo 1·00
revascularisation because of unsuitable anatomy or
refusal. 16 of the 19 deaths were judged to be definitely
or most likely due to cardiac reasons, and three were
due to non-cardiac reasons (cancer, septic shock, and
Proportion without death or MI

haemorrhagic shock; one in the optimum medical 0·95

group, and two in the invasive group, neither
intervention related).
Figure 2 shows the event-free survival curves and the
time to death and myocardial infarction during follow-
0·90
up. Differences in early (30-day) and late (2–6-month)
events for both study groups are shown in figure 3.
These results point to an increased risk of death early in
follow-up in the invasive group, but fewer hospital
admissions for acute coronary syndrome or myocardial 0·85 p=0·93
infarction later on. Overall, four deaths (three in the
invasive group, one in the optimum medical group) and
six myocardial infarctions (three in each group) were
direct complications of revascularisation procedures
resulting in an overall revascularisation mortality of 0·80
2·5%. Additional cardiovascular complications leading 0 50 100 150 200
to hospital visits occurred in six patients in the optimum Days after randomisation
medical group and nine in the invasive group (stroke or Number at risk
syncope in two versus three, peripheral vascular disease Invasive group 153 140 136 133 131*
in one versus two, congestive heart failure in two versus
Optimum medical 148 138 134 126 126*
three, and others in one versus one). group

Discussion
This prospective randomised study addressed the
management of elderly patients with chronic angina
refractory to standard antianginal drug therapy. Unlike
previous trials, selection of patients was based on
clinical presentation and not on angiographic findings;
the study compared contemporary optimised medical
and revascularisation strategies, which included
angioplasty and surgery wherever justified; and its main
goal was quality of life assessment based on symptoms, a
comprehensive questionnaire, and major adverse cardiac
events. Patients in both groups were clinically improved
and had better general well-being during follow-up, but
Figure 2: Event-free survival (no major adverse cardiac events
[MACE]) and time to death and non-fatal myocardial infarction
during 6-month follow-up
MI=myocardial infarction. *Number at risk at 6 months’ follow-up (ie, at
least 151 days after randomisation, mean 185 days [SD 13])
this improvement was greater after revascularisation. A
third of patients in the optimum medical group needed
revascularisation during follow-up for uncontrollable
symptoms. Three quarters of patients selected for an
invasive approach were good candidates for
revascularisation. Overall, the invasive approach was

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40
35
30
Number of events
25
20
15
10
5 measures,23 showing a greater improvement in physical
0 angioplasty.
Invasive Optimum Invasive Optimum
medical medical
0–30 days 2–6 months
Hospital admission for Hospital admission for
ACS without revascularisation ACS with revascularisation
Non-fatal myocardial infarction Death
Figure 3: Comparison of early (30-day) and late (2–6-month)
major adverse cardiac events between groups
followed by a significantly lower rate of major adverse
cardiac events, particularly non-fatal ischaemic events,
and carried only a small intervention risk. This risk was
highest for patients in the invasive group who had an
unsuitable anatomy for revascularisation or who
refused it.
Previous randomised studies comparing CABG
surgery1–4 or PCI5–7 with medical therapy studied
younger patients, mostly with an average age of about
65 years, and based inclusion on a “suitable” coronary
anatomy. Most of these were mortality trials8 and did
not prospectively collect data on rehospitalisation for
unstable angina or quality of life. The elderly patients in
the present study represent a high-risk population and
the findings confirm a benefit in quality of life,
symptomatic status, and non-fatal ischaemic events.
However, it showed a small excess risk early on, as has
been seen previously after high-risk CABG surgery,8
angioplasty,18 and in shock patients.19 The study was not
planned as a mortality trial and was too small and the
primary endpoint too early to show the long-term
mortality benefit that might be expected on the basis of
the large reduction in non-fatal ischaemic events after
the first 30 days. Noteworthy, however, is the fact that
half the cardiac deaths in the invasive group occurred in
patients unwilling or unsuitable for revascularisation,
resulting in a high mortality rate for that subgroup.
Optimised medical therapy including antiaggregants and
lipid-lowering drugs was advised during the
randomisation visit, but no particularly high doses were
prescribed in these elderly patients—unlike in the
atorvastatin versus angioplasty trial.20 By contrast with
those results, we noted an obvious reluctance of patients
or their treating physicians to continue lipid-lowering
drugs in this elderly population. Otherwise, a
remarkably intense drug regimen was followed for up to
6 months in the medical group, which was reduced
significantly after revascularisation in invasive patients.
This drug therapy significantly reduced symptomatic
status and improved quality of life, but a third of
patients needed revascularisation for uncontrolled
symptoms.
THE LANCET • Vol 358 • September 22, 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.
ARTICLES
Previous assessments of quality of life in context with
antianginal therapy have been based mainly on
surrogate endpoints such as freedom from angina,
number of antianginal medications, or return to work.
However, the need for more reproducible and
standardised disease-specific instruments of quality of
life assessment has been recognised and used recently in
patients after CABG surgery,21,22 PCI,21–24 and medical
therapy.25
The Angioplasty Compared to Medical Therapy
(ACME) trial was the first randomised trial to examine
the effect of different therapies on quality of life
and psychological measures in patients assigned
The larger second Randomised
Intervention Treatment of Angina (RITA-2) trial
confirmed these findings up to 1 year, particularly for
physical functioning, vitality, and general health. An
attenuation of this improvement over 3 years was partly
attributed to 27% of medically treated patients receiving
revascularisation during follow-up.23 In the present
study, similar tools for quality of life assessment were
applied to an elderly population and confirmed an
overall improvement in general health and pain status
with both medical and revascularisation therapies. This
effect was somewhat greater after revascularisation in
both patient groups, minimising the difference between
treatments in overall results. The improvements in
symptomatic status and general well-being is
particularly important in view of the fact that quality of
life is of primary importance for 80-year-old patients—
more important than prolongation of life.
Several retrospective registry reports on revasc-
ularisation in elderly patients have shown that CABG26–29
and PCI30–32 can be done with an acceptable risk in
selected patients, but that the frequency of in-hospital
complications and mortality is increased compared with
younger patients. The authors of these reports based
their findings on patients referred for such interventions
with suitable coronary anatomy, and thereby differ
substantially from clinical patients as studied in the
present trial.28,32 For a practising physician facing an 80-
year-old patient with angina pectoris despite standard
therapy, the main question is whether to send this
patient for invasive assessment or not. The decision
might depend on the patient’s general health, cardiac
risk profile, and on comorbidity. Since participation in
our study was offered to patients at this point, our
patients are much more representative of patients seen
in outpatient clinics than previously reported registry
patients. Hence, the recorded rates of about 30% for
non-performable revascularisation and of 36% for
needed revascularisation despite optimum medical
therapy are relevant, as is the finding that both therapies
improve symptoms and general well-being in elderly
patients.
This study included patients with anginal chest pain
despite standard medical therapy. Still, 7% of patients
showed no significant coronary-artery stenoses despite
“anginal” chest pain, probably because of hypertensive
or hypertrophic heart disease. Since masking of therapy
was not possible, a bias towards invasive therapy during
follow-up in medically treated patients cannot be
excluded, but overall results with regard to major
adverse cardiac events are strongly supported by
findings of quality of life assessment in the present
study. Quality of life could not be assessed fully in all
patients at follow-up, leaving a minor uncertainity about
the absolute benefit of each treatment. However, the
955
ARTICLES
consistency of changes in quality of life scores and
clinical parameters strongly supports the overall
findings. To assess more fully the effect of both
treatment strategies on quality of life and outcome, a
prolonged follow-up is in process. Furthermore, a
prospective evaluation of cost, the effect of full versus
culprit-lesion revascularisation, different subgroups, and
detailed quality of life analyses are planned and in
progress.
We showed that patients aged 75 years or older with
angina despite standard medical therapy benefit from
both optimised medical and revascularisation therapy in
terms of symptom relief and quality of life. Additionally,
findings suggest that these patients should be offered an
invasive assessment despite their high cardiac risk profile
and previous revascularisations. If coronary anatomy is
suitable for revascularisation, as it was in 74% of
patients in this study, this treatment should be done
with the object of improving symptoms and quality of
life more than with antianginal drugs alone. Patients
have to be aware, however, of a peri-interventional
mortality hazard which, based on current methodology
and expertise, is small.
The TIME Investigators
Writing Committee—M Pfisterer, O Bertel, P Erne, J J Goy, G Kuster,
P Rickenbacher, C Schindler, R Schönenberger
Steering Committee—M Pfisterer (Principal Investigator), U Allemann,
W Amann, W Angehrn, O Bertel, P Erne, W Estlinbaum, J J Goy, T
Moccetti, P Rickenbacher, F Ricou, R Schönenberger
Investigators and centres—M Pfisterer, P Buser, S Osswald,
H R Zerkowski, W Brett, U Knutti, C Kaiser (University Hospital
Basel); A Vuillomenet, S Yoon (Kantonsspital Aarau); F Eberli
(University Hospital, Bern); H Schläpfer, Ch Röthlisberger
(Regionalspital Biel); P Rickenbacher, N Hess (Kantonsspital
Bruderholz); P Dubach, S Sixt (Kantonsspital Chur); U Allemann,
C Grädel (Clara Hospital, Basel); J J Goy, E Eeckhout (University
Hospital, Lausanne); W Estlinbaum (Kantonsspital Liestal);
T Moccetti, D Moccetti (Cardiocentro Lugano); P Erne, U Klöter
(Kantonsspital Luzern); W Angehrn, H Rickli (Kantonsspital
St Gallen); O Bertel, O Friesewinkel, M Genoni, B Naegeli (Triemli
Hospital, Zürich); W Amann, W Kiowski, M Bötschi, M Turina
(University Hospital, Zürich)
Local investigators and TIME Data Centre, University Hospital Basel—
F Bader, Ph Dreifuss, U Forrer-Christ, A Hagmann, G Kuster,
R Osterwalder, F Mughal, L Schöb, M Pfisterer
Critical Events Committee/Data and Safety Monitoring Board—
D Burckhardt (Basel), F Follath (Zürich), W Rutishauser (Geneva)
Statistics—Ch Schindler, L Grize (Institute for Social and Preventive
Medicine, University Hospital, Basel, Switzerland)
Quality of life advisors—R Schönenberger (Kantonsspital Solothurn,
Switzerland); D Mark (Duke University, Durham, NC, USA)
Acknowledgments
We thank D Mark for his support in quality of life assessment and
analysis, and E Stalder for preparing the paper.
This study was supported by grants from the Swiss Heart
Foundation Berne, Switzerland, and the ADUMED Foundation,
Switzerland. The study was sponsored by the Working Group of
Coronary Interventions and Acute Coronary Syndromes of the Swiss
Society of Cardiology.
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Clinical picture: Digging for gold

Lars Wesslén, Goran Wegenius

A 63-year-old man was clinically diagnosed with pneumonia on a house call. His
rectal temperature was 39˚C, and crackling rales were heard over the right lung
base. He was successfully treated with penicillin V, even though a nasopharyngeal
swab grew Haemophilus influenzae. At follow up one month later, radiographs of the
chest (figure) revealed a small high density structure located in the lower right lobe.
It had features compatible with a pivot tooth, and was surrounded by a cavity
measuring 3 cm in diameter. The patient recalled a visit to his dentist 18 months
earlier when he had swallowed two gold teeth during implantation procedures. No
respiratory symptoms were noted at the time and the following weeks he used a
wash pan trying to retrieve the lost valuables in his faeces without any luck.
Eventually, he stopped searching. A fibreoptic bronchoscopy was done without
finding anything unusual. At thoracotomy a gold tooth was located 2 mm beneath
the visceral pleura of the mediobasal part of the right lower lobe and removed by a
small incision. The fate of the second gold piece remains a mystery.
Department of Infectious Diseases (L Wesslén MD), and Department of Diagnostic Radiology
(G Wegenius MD), Uppsala University Hospital, Uppsala, SE-751 85, Sweden

THE LANCET • Vol 358 • September 22, 2001 957

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