European Heart Journal (1996) 17 {Supplement G), 25-29

Angina pectoris in patients with a history of

myocardial infarction
P. Sellier
From the Service de Readaption Cardiaque, Hopital Broussais, Paris, France
The existence of a history of myocardial infarction (MI) in
patients with angina pectoris is frequently associated with
certain patient characteristics, including an established
history of coronary artery disease (CAD), depressed left
ventricular function in some patients and multivessel
coronary disease.
Angina is a symptom which reveals the persistence or
recurrence of myocardial ischaemia. It is uncertain whether
persistent myocardial ischaemia after MI is an adverse
prognostic factor. In fact, the most important known
prognostic factor is left ventricular function.
Before choosing an anti-anginal therapy in patients with a
history of MI, coronary angiography should be performed
in order to investigate the possibility of left main or
multivessel CAD. Angina patients with impaired left ven-
tricular function may benefit from revascularization but the
prognostic value of percutaneous transluminal coronary
angioplasty in these patients remains to be assessed. Medi-
cal anti-anginal therapy for symptoms, added to routine
background treatment, is indicated when the results of
revascularization are unsatisfactory or if there is an absence
of indication, or a contra-indication, for revascularization
procedures. Particular attention should be paid to the
possible additive negative inotropic or chronotropic effects
of /?-blockers and certain calcium antagonists on the
myocardium
(Eur Heart J 1996; 17 (Suppl G): 25-29)
Key Words: Angina pectoris, myocardial infarction,
calcium channel blockers
Introduction
Angina pectoris and myocardial infarction (MI) are
among the most frequently observed aspects of coronary
artery disease (CAD) and in some patients these two
complications may occur successively. It has been re-
ported that half of the patients with MI will have angina
pectoris during follow-up
[1
~
71
, while databases from
some studies show that, on average, half of the patients
with angina pectoris have a history of MI (Table 1).
Among these patients, some have had an MI
very recently and this early post-infarction angina is an
acute form of CAD that poses specific problems in terms
of investigation and therapeutic approach'
1
''. However,
in this review, the objective is to focus only on patients
with angina pectoris and history of a previous MI (at
least 1 month before).
Three questions remain to be answered: (1) what
are the main characteristics of these patients with angina
pectoris and a history of MI; (2) what is the prognosis
related to these characteristics; (3) what is the best
therapeutic approach with regard to investigation,
revascularization procedures and medical therapy?
Correspondence: Dr Philippe Sellier, Service de Readaption
Cardiaque, Hopital Broussais, 96 rue Didot, 75014 Paris, France.
Table 1 Frequency of a history of myocardial infarction
in patients with anginal pectoris
Study No. of patients
No. of patients with
a history of MI
CASS'
8
'
ECSSG
[9)
VA study"
01
780
768
686
467
349
411
59
45
60
CASS = Coronary Artery Surgery Study; ECSSG = European
Coronary Surgery Study Group; Ml=myocardial infarction;
VA = Veterans Administration.
Characteristics of patients
Patients with angina pectoris and a history of MI have
some special characteristics. For example, the risk of
recurrence of angina pectoris after MI is increased by
50% (79% vs 52%, P<001)
[3]
in patients who have a
previous history of angina. It has also been shown that
recurrent angina after MI is more common in patients
with non-Q wave infarction
112
\ in whom the risk is
increased by 40% (65% vs 46%, P<00001).
Furthermore, it has been shown that angina
pectoris is more frequently observed in the follow-up
after MI in patients with two- (68%) or three-vessel
0195-668X/96/OG0025 + 05 $25.00/0 1996 The European Society of Cardiology

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26 P. Sellier
disease (77%) than in patients with one-vessel disease
(36%, i'<0025). This risk is also increased in patients
with proximal left anterior descending (LAD) lesions
131
.
On average, patients post-MI usually exhibit
some degree of depressed left ventricular function, pro-
portionally related to the extent of necrosis, but such
differences do not appear to be linked to the presence or
absence of angina pectoris'
31
. Furthermore, it has been
shown that left ventricular function in patients with
one healed MI did not differ between patients with
or without exercise-induced angina pectoris and ST
depression during exercise testing
1
'
31
.
In summary, the existence of a history of MI in
patients with angina pectoris is frequently associated
with certain patient characteristics, including an estab-
lished history of CAD, depressed left ventricular
function in some patients and multi-vessel disease.
Prognosis
Angina pectoris is a symptom revealing the persistence
or the recurrence of myocardial ischaemia after MI.
However, many studies have demonstrated that myocar-
dial ischaemia is mostly asymptomatic and is four-times
more frequent than symptomatic disease'
141
. Therefore,
assessment of the prognosis of patients with angina
pectoris and a history of MI is more accurately ad-
dressed by evaluating the importance of myocardial
ischaemia itself. This can be done by any non-invasive
investigation routinely used for detection of myocardial
ischaemia, of which exercise testing is the most fre-
quently performed. In 1979, Theroux et a/.'
151
reported
that the presence of ST depression during an early
exercise test after MI was predictive of subsequent
cardiac events. Since then, many studies have been
performed to assess the predictive value of exercise-
induced ischaemia soon after MI, often with negative
results'
16
'. The presence of ischaemic episodes on 24-h
ambulatory ECG monitoring has been shown to predict
cardiac events'
171
, but those events which are predicted
are often 'soft' events, such as coronary angioplasty
(PTCA) or coronary artery bypass surgery (CABG), and
not 'hard' events, such as death or recurrent MI. More
recent studies, using left ventricular contraction abnor-
malities detected by echocardiography as a marker of
ischaemia, have shown interesting results as regards
prognosis evaluation'
181
. In one study, the clinical out-
come was predicted with a good sensitivity (80%) and a
high specificity (95%). However, in general, the presence
of angina pectoris and, above all, myocardial ischaemia
after MI, is a controversial prognostic factor, with
probably little predictive value of death and recurrent
MI.
If the prognostic value of myocardial ischaemia
is unclear, left ventricular function is definitely an
important prognostic indicator. Cardiac mortality in the
first year after MI is directly related to left ventricular
ejection fraction (Fig. 1), with a rapidly increasing risk
in the case of ejection fraction <0-40'
191
. As has been
0.15 0.25 0.35 0.45 0.55 0.65 0.75 0.85
Left ventricular ejection fraction
Figure 1 The relationship between left ventricular ejec-
tion fraction and 1-year prognosis after myocardial in-
farction. (Reproduced with permission from Gadsboll
etal?
9
K)
indicated above, patients with angina pectoris and a
history of MI generally have some degree of depressed
left ventricular function. Long-term prognosis is there-
fore directly related to left ventricular ejection fraction,
with a high risk of subsequent cardiac events in the case
of severely depressed left ventricular function.
Treatment of angina pectoris after
myocardial infarction
Medical treatment
Routine background medical treatment post-MI is now
well established and many classes of drugs have a
beneficial effect on the long-term prognosis and symp-
toms of these patients'
201
. /?-blockers, anti-platelet
agents, anti-coagulants and cholesterol-lowering agents
have proven efficacy in secondary prevention (Table 2).
To these drugs, cardiac rehabilitation must be added
as being a beneficial treatment in post-MI patients'
201
.
On the other hand, class-I anti-arrhythmics have a
detrimental effect'
2
'
1
. More recently, the efficacy of
angiotensin converting enzyme inhibitors has been dem-
onstrated, especially for prevention of left ventricular
re-modelling and long-term improvement of prognosis
in patients with depressed left ventricular function'
221
.
Among the different drugs which may be pre-
scribed in post-MI patients, particularly in cases of
recurrent angina pectoris, the position of calcium chan-
nel blockers is questionable. Although their anti-anginal
efficacy is proven, no overall beneficial influence on
long-term prognosis has been demonstrated'
201
. But this
effect differs according to the type of agent which is
used'
231
. The analysis of the different published trials
(Table 3) shows a trend in favour of agents that decrease
heart rate (diltiazem and verapamil) in terms of long-
term mortality (risk ratio: 0-95, 95% confidence interval:
0-82-1 09, ns) and reinfarction rate (risk ratio: 0-79, 95%
confidence interval: 0-67-0-94, /><001). However,
agents such as some dihydropyridines that increase
heart rate have been shown to be associated with a
non-significant trend towards a detrimental effect on
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Angina pectoris in patients with MI 27
Table 2 Cumulative meta-analyses of treatments of myocardial infarction and
secondary prevention. (Reproduced with permission from Lau et a\J
201
)
Treatment No. of trials No. of patients
Cumulative odds
ratio
P value
Anti-coagulants
Rehabilitation
^-blockers
Cholesterol lowering
Anti-platelet agents
Ca
2+
channel blockers
Class I anti-arrhythmics
12
23
17
8
10
6
11
4975
5022
20 138
10 775
18411
13 114
4336
0-78 (0-67-0-90)
0-80 (0-67-0-95)
0-81 (0-73-0-89)
0-86 (0-79-0-94)
0-90 (0-82-1-00)
101 (0-90-112)
1-28 (1-02-1-61)
<0001
0012
<0001
<0-001
0051
0 91
0-03
Table 3 Effects of calcium antagonists on long-term prognosis after myocardial
infarction. (Reproduced with permission from Yusufet a\/
23/
)
No. of
patients
Odds ratio
(95% confidence
interval)
P value
Mortality
Dihydropyridines
Verapamil + diltiazem
Reinfarction
Dihydropyridines
Verapamil + diltiazem
714
871
257
564
116
0-95
119
0-79
0-99-1-35
0-82-1-09
0-92-1.53
0-67-0-94
ns
ns
ns
<001
mortality (risk ratio: 1-16, 95% confidence interval:
0-99-1-35, ns) and reinfarction rate (risk ratio: 119, 95%
confidence interval: 0-92-1-53, ns).
Within calcium channel blockers, agents which
decrease heart rate have no effect'
241
or even a slightly
detrimental effect
[25]
on long-term prognosis in patients
with congestive heart failure.
The presence of angina pectoris in patients with a
history of MI suggests that the routine background
treatment is insufficient. In these conditions many anti-
anginal drugs may be of benefit in controlling symp-
toms, as well as myocardial ischaemia. Among these,
nitrates, especially long-acting nitrates, or calcium
antagonists may be prescribed, usually on top of optimal
/?-blocker background treatment. Long-acting nitrates
are an interesting alternative which are widely used,
especially with /?-blockers, for the treatment of angina
pectoris. However, reductions in efficacy have been
demonstrated in long-term therapy, due to the appear-
ance of nitrate tolerance'
261
. Therefore, the control of
symptoms in these patients is often based on additional
treatment with calcium antagonists. Of these agents,
amlodipine'
271
(Fig. 2) and verapamil'
71
(Fig. 3) have
proven symptomatic efficacy in this population of
patients. It has also been demonstrated that calcium
antagonists are efficient in reducing the frequency of
silent ischaemic episodes. Furthermore, they have com-
plementary effects when associated with /J-blockers,
since the latter are effective for the treatment of ischae-
mic episodes associated with an increase in heart rate,
while calcium antagonists are more effective for ischae-
mic episodes not related to such an increase'
281
. They
may be used in addition to /?-blockers or as mono-
therapy, when /?-blockers are contra-indicated. In the
latter case, the choice of the calcium antagonist must be
based on its impact on long-term prognosis. Although
diltiazem has been shown to result in a reduction in
cardiac events for a period of between 12 and 52 months
post-MI, this was counter balanced by an increase in
such events in those patients with left ventricular dys-
function'
251
. Therefore, the only drug of this class to
have proven efficacy at this time is verapamil.
In the case of an addition to ^-blockers, no data
are available on the potential effects of combination
8 12 16
Time of day (h)
20 24
Figure 2 The total number of anginal attacks/h during
2-week baseline and final 2 weeks of amlodipine treat-
ment. Based on diary data from evaluable post-myocardial
infarction patients (baseline n=47). *=baseline; O= final
(Reproduced with permission from Taylor'
27
'.)
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28 P. Sellier
sCO
"c
a
V
a
43
l
u
l
a
B
3
70
60
50
40
30
20
10
c
^ * "
if
~K> P< 0.002
7
/
( 1 1 1 1
Placebo
(n = 897)
Verapamil
(n = 878)
1
90 180 270
Days
360 450 540
Figure 3 Incidence of angina pectoris after myocardial
infarction during the 18-month follow-up (DAVIT II trial)
according to treatment. (Reproduced with permission from
Jespersen et a/.'
71
.)
therapy on prognosis. However, it may be supposed that
y?-blockers and calcium antagonists with negative
chronotropic action, and perhaps those with no effect on
heart rate, have a beneficial additive effect on prognosis.
However, key limiting factors in long-term therapy are
the additive effects of both classes of drugs on contrac-
tility, heart rate (for those with a negative chronotropic
effect), blood pressure and atrioventricular conduction,
which should lead to some caution in initiating and
continuing such combination treatment because of the
high frequency of impaired left ventricular function in
post-MI patients.
Calcium antagonists have another interesting
effect in patients with angina pectoris who are likely to
have a depressed myocardial function, in that it has been
shown that they may improve diastolic function'
291
,
which is often altered in patients with CAD.
Thus, the medical treatment of angina pectoris in
patients with a history of MI may include nitrates or
calcium antagonists on top of the background treatment
(usually including /?-blockers) that is routinely pre-
scribed post-MI. In terms of being effective both on
symptoms and prognosis, the best choice is a calcium
antagonist with a negative chronotropic effect (or, at
least, no positive chronotropic effect), although one
must be cautious about the additive effects of both
classes of drugs on the myocardium. In case of contra-
indication to /?-blockers, verapamil has proven sympto-
matic and prognostic efficacy when left ventricular
systolic function is not depressed. However, while cal-
cium antagonists have a beneficial effect on symptoms,
there is no evidence at the present time that any drugs of
this class have a beneficial effect on prognosis.
Revascularization procedures
No specific data concerning the prognostic influence of
myocardial revascularization for angina pectoris after
MI in large populations are available. However, large
trials comparing medical and surgical treatment in
patients with angina pectoris include a significant pro-
portion of patients with a history of MI and this enables
us to draw some conclusions. From these data it has
been proven that patients who may benefit from aorto-
coronary bypass surgery include those with an ejection
fraction <0-50'
81
, patients with two- or three-vessel dis-
ease, including proximal LAD lesions'
91
and patients
with left main coronary artery lesions'
101
.
Even if these results do not exclusively concern
patients with a history of MI, they may be the basis of a
routine approach towards angina pectoris in patients
with a history of MI. The first step in such a therapeutic
approach is to perform coronary angiography and then
to refer patients to surgery if coronary artery lesions and
left ventricular function indicate that this is appropriate.
PTCA represents an alternative means of myo-
cardial revascularization but it is contra-indicated in
some cases, such as left main stenosis. It is also less likely
to obtain complete revascularization than surgery in
multivessel disease and its usefulness is limited by the
restenosis rate. PTCA also suffers from the lack of data,
based on large populations, regarding the possible bene-
ficial effect of revascularization on long-term prognosis
in post-MI patients'
301
. Even if the concept of an 'open
artery' is interesting, no data are available regarding the
value of re-opening the infarct-related artery in post-MI
patients. The only clear indication for PTCA is the
persistence of symptoms of angina pectoris, in spite of
optimal anti-anginal therapy associated with one- or
two-vessel disease and nearly normal left ventricular
function.
In summary, the presence of angina pectoris in
patients with a history of MI is an indication first to
perform coronary artery angiography, due to the high
incidence of two- or three-vessel disease and depressed
left ventricular function in this population. The decision
as to whether to undertake revascularization and the
choice of method used should be based on the extent
of coronary artery lesions and left ventriculography,
together with findings from clinical and non-invasive
investigations.
Medical anti-anginal therapy for symptoms,
added to routine background treatment, is indicated
when the results of revascularization are unsatisfactory
or if there is an absence of indication or a contra-
indication for revascularization procedures.
Conclusions
Patients with angina pectoris and a history of MI are
likely to have a history of previous angina pectoris or a
history of non-Q-wave MI and often have two- or three-
vessel disease and depressed left ventricular function.
Despite the fact that the presence of symptoms
or the persistence of myocardial ischaemia after MI has
a questionable effect on long-term prognosis, there is an
accumulation of data suggesting that they have little
impact on subsequent cardiac 'hard' events.
The best therapeutic approach to these patients,
based on the main characteristics of this population, is
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Angina pectoris in patients with MI 29
to perform coronary artery angiography followed by
revascularization by CABG or PTCA, if necessary,
according to the extent of lesions and symptoms and to
add long-acting nitrates or calcium antagonists to the
usual background /?-blocker treatment, paying particu-
lar attention to the possible additive negative inotropic
or chronotropic effects of /?-blockers and calcium antag-
onists on the myocardium. If yS-blockers are contra-
indicated, calcium antagonists which have a proven
beneficial effect on symptoms and long-term prognosis
should be used.
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d
e
d

f
r
o
m