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Review Article
Management of patients with myocardial infarction and
hypertension
G. Y. H. Lip, C. Lydakis and D. G. Beevers
University Department of Medicine and Department of Cardiology, City Hospital, Birmingham, U.K.
Introduction
A patient presenting with acute myocardial infarction
and severe or uncontrolled hypertension represents an
emergency situation requiring prompt and accurate
evaluation of both conditions, and treatment should be
neither inadequate nor overzealous. The acute coronary
event may be accompanied by raised blood pressure
either due to acute stress or secondary to long-standing
but possibly undiagnosed hypertension. Very rarely,
such a presentation may be part of a true hypertensive
emergency, such as malignant phase hypertension,
hypertensive encephalopathy or dissection of the aorta.
Whilst both myocardial infarction and uncontrolled
hypertension require treatment, the question is not only
what should I use to lower the pressure but also how
much time do I have in order to obtain the potential
benefit from thrombolytic treatment; indeed immediate
and rapid normalization of blood pressure is not the
goal of initial therapy in most cases. Treating one
condition but not the other also creates potential problems. For example, giving thrombolytic therapy to a
patient with severe hypertension may increase the risk of
cerebral bleeding. By contrast, treating the hypertension
alone and ignoring the heart attack may result in
complications secondary to myocardial infarction,
including severe cardiac dysfunction, arrhythmias and
valve dysfunction. This has led to some debate and
confusion over the management of such patients, leading
to suboptimal care and dierent treatment policies in
dierent coronary care units. Some of the treatments
that are being employed have even been shown to be
dangerous.
Manuscript submitted 6 August 1999, and accepted 13 October
1999.
Correspondence: Dr G. Y. H. Lip, University Department
of Medicine and Department of Cardiology, City Hospital,
Birmingham B18 7QH, U.K.
0195-668X/00/141125+10 $35.00/0
Pathophysiology
An understanding of the perfusionregulation of the
heart is necessary to appreciate the pathophysiological
basis of treating patients with myocardial infarction and
uncontrolled hypertension. The cerebral and coronary
vascular beds have the ability of autoregulation, so that
organ perfusion is kept constant within a range of
systemic blood pressures.
For example, cerebral blood flow normally remains
stable at 50 ml . min 1 . 100 g 1 of brain tissue[1]. However, cerebral blood flow in hypertensive patients is not
dierent from that found in normotensive subjects,
which reflects a shift of the autoregulation flow curve to
the right within the range of mean arterial pressure from
100 to 180 mmHg (Fig. 1(b)), whilst in normotensives
the corresponding range is 60 to 120 mmHg. This
explains why patients with long-standing uncontrolled
hypertension cannot tolerate rapid great reductions in
blood pressure even to that within normotensive levels.
In the myocardium, a similar autoregulatory mechanism is present, although several dierences exist between
the vascular trees of the brain and heart. Cerebral blood
flow is profoundly influenced by changes in arterial
carbon dioxide tension[2], and in cases of ischaemia the
brain compensates by extracting more oxygen from the
blood[3]. By contrast, myocardial blood flow depends
upon arterial oxygen saturation[4] and coronary sinus
oxygen saturation at rest is usually around 30%,
2000 The European Society of Cardiology
1126
G. Y. H. Lip et al.
Review
Table 2
1127
Drugs for hypertensive emergencies with acute coronary event. (Adapted from ref.[16])
Drug
Dose
Nitroglycerin
0580 g . kg 1 min 1
(i.v. infusion)
Labetalol
2 mg . min 1 to total of
2 mg . kg 1 (i.v. infusion)
0380 g . kg 1 min 1
(i.v. infusion)
515 mg . h 1 (i.v. infusion)
Nitroprusside
Nicardipine
Comments
Administer by syringe pump (drug
is absorbed by soft plastic containers)
Avoid in cardiac failure, asthma,
second or third degree block
Requires careful monitoring
New agent, still under evaluation,
may cause tachycardia
Nifedipine
Nifedipine, a calcium channel antagonist of the 1,4
dihydropyridine class, has frequently been used in cases
where an immediate reduction of blood pressure seemed
desirable. The onset of action of nifedipine has been
reported to be within 5 to 30 min, with the peak eect
within 30 min to 1 h[12]. The ease of administration
(orally), its eectiveness with a rapid onset of action and
the lack of side eects (in early reports) resulted in its
recommendation as the first line drug for hypertensive
emergencies[1820]. The use of sublingual nifedipine
should nevertheless be discouraged, as it is not absorbed
by the oral or oesophageal mucosa, and the liquid
released from the crushed nifedipine capsule is erratically absorbed later, resulting in fluctuating eects,
including a sudden and rapid fall in blood pressures.
The initial studies in favour of nifedipine in the
treatment of hypertensive emergencies were small (2030
patients each) and all showed an eective reduction of
blood pressure without severe adverse eects, especially
since no dangerous hypotension was reported[2124].For
example, Komsuoglu et al.[24] studied 22 patients with
hypertensive encephalopathy who were administered
20 mg liquid nifedipine orally (equivalent to biting a
capsule), where the mean blood pressure fell from 236/
121 mmHg to 172/96 mmHg after 30 min with no significant side eects. In a further study of 25 patients with
Eur Heart J, Vol. 21, issue 14, July 2000
1128
G. Y. H. Lip et al.
Beta-blockers
Oral or intravenous treatment with beta-adrenoceptor
blockers lowers the blood pressure within hours[37]. They
also have important antiischaemic eects, so that they
should be considered as first line therapy in patients with
myocardial infarction, in the absence of contraindications. These drugs protect the jeopardized ischaemic
myocardial tissue by reducing oxygen demand (by
1530%) due to their eects in lowering heart rate,
blood pressure[38] and cardiac output[39]. Furthermore,
the beta-blockers have antiarrhythmic properties and
can cause favourable shunting of blood away from
Review
Table 3
1129
Study
Early (immediate initiation)
Goteborg Metoprolol Trial[45]
MIAMI trial[46]
ISIS-1[47]
Late (initiation 528 days later)
Norwegian Multicentre Study[48]
BHAT[49]
Year
1981
1985
1986
1395
5778
16 027
1981
1982
1884
3837
Treatment period
Reduction in mortality
Age (years), (5)
Metoprolol
Metoprolol
Atenolol
90 days
15 days
7 days
Timolol
Propanolol
17 months (mean)
25 months (average)
Beta-blocker
ACE inhibitors
ACE inhibitors lower the blood pressure by decreasing
elevated systemic vascular resistance without inducing
reflex sympathetic activation[50]. They also exert antiischaemic eects by the reduction of myocardial oxygen
demand, reduction of ventricular wall tension and improvement of coronary blood flow[50]. The vasodilator
and neurohormonal (through inhibition of the reninangiotensin axis) eects of ACE inhibitors and their
eect on long term-remodelling may account for their
favourable properties in patients suering from acute
myocardial infarction[51,52].
The beneficial eects of the ACE inhibitors on mortality reduction were shown in randomized trials with
both late (after days) (SAVE[53], AIRE[54], TRACE[55])
and early (within hours) (SMILE[56], CONSENSUS-II[57],
GISSI-3[58], ISIS-4[59], CCS-1[60]) administration. Overall, these trials indicate a definite benefit of saving about
five lives for every 1000 patients treated[61].
The administration of ACE inhibitors in patients
presenting with acute myocardial infarction and hypertension has both a good early safety profile, especially
since dangerous hypotension was not a significant
Nitrates
The antihypertensive and antiischaemic eects of
nitrates make them suitable candidate drugs for treating
patients with acute myocardial infarction (with or without raised blood pressure). Since their antianginal eect
is well documented, the research interest has been
focused in recent years in hard-end points like infarct
size, remodelling and mortality.
In a meta-analysis of Yusuf et al.[62] of ten trials of
intravenous nitroglycerin and nitroprusside that included over 2000 randomized patients, a significant
reduction of 35% in mortality (albeit with wide confidence limits) in the first week was shown, with the
benefit lasting up to several months. This beneficial
eect of nitrates shown in the pre-thrombolysis era,
however, appeared to be absent in recent large trials in
patients receiving conventional thrombolytic treatment[58,59] (Table 4). Nevertheless, in the acute phase of
myocardial infarction, whether or not accompanied by
raised blood pressure, nitrates are a safe treatment
option, and may be particularly useful if heart failure is
present.
Calcium antagonists
The antiischaemic and antihypertensive actions of the
calcium antagonists are mainly due to arteriolar
Eur Heart J, Vol. 21, issue 14, July 2000
1130
G. Y. H. Lip et al.
Table 4 Recent trials of nitrates in acute myocardial infarction. (ISMN: isosorbide mononitrate, ISDN: isosorbide
dinitrate)
Year of
publication
n
(randomized)
GISSI-3[58]
1994
ISIS-4[59]
Morris et al.[82]
Nitrate
Duration
End-points
19 394
6 weeks
1995
58 050
1 month
1995
301
captopril up to
50 mg2 vs placebo.
ISMN up to 60 mg1
vs placebo. Magnesium
sulphate i.v. vs placebo
ISDN i.v. vs placebo
for the first three days
6 weeks
Verapamil
Diltiazem
Nifedipine
Table 5
1988
1993
1986
1988
1984
1990
SPRINT-I[66]
SPRINT-II[67]
Gibson et al.[68]
MDPIT[69]
DAVIT-I[70]
DAVIT-II[71]
1996
1986
HINT[65]
CRIS[72]
1985
Year of
publication
TRENT[64]
Trial
531
1775
1436
2466
576
1006
2276
338
4491
n
(treated)
7 days after MI
Immediately after MI
2472 h after MI
048 h after MI
Unstable angina
024 h after MI
Clinical setting
Diltiazem 3090mg1 vs
placebo
Diltiazem 240 mg1 vs
placebo
Nifedipine 60 mg1 vs
placebo
Nifedipine 30mg1 vs
placebo
Nifedipine 10 mg3 vs
placebo
Nifedipine 10 mg6 vs
metoprolol 100 mg2 vs
combination vs placebo
Calcium antagonist
Mean 16 months
12 months
Mean 15 months
14 days
6 months
1 year
48 h
28 days
Duration
End-points Results
Review
1131
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G. Y. H. Lip et al.
Recommendations
In a patient presenting with acute myocardial infarction
and severe hypertension, the appropriate treatment
should include the initiation of intravenous nitrates,
with intravenous labetalol, sodium nitroprusside and/or
nicardipine as alternatives, especially in very severe
hypertension or hypertensive emergencies. The reduction of blood pressure should not be abrupt, and a
gradual reduction over a period of 2448 h is recommended, so that further myocardial or brain ischaemia is
avoided. Sublingual nifedipine, which has usually been
considered as a first line drug, should be avoided, in view
of the negligible oral absorption and unpredictable
hypotensive eects.
In the majority of patients presenting as an emergency
with acute myocardial infarction and in hypertension
without signs of other acute target organ damage,
hypertension does not necessarily represent an acute
major threat. Treatment should be aimed at relieving
symptoms, protecting the ischaemic but potentially
viable myocardial tissue and reducing mortality. Blood
pressure should be reduced to <160/110 mmHg before
administration of thrombolysis, although if available,
primary angioplasty is an option for reperfusion in
patients with high blood pressure and/or the perceived
risk of stroke if thrombolysis is unacceptable. In our
evidence-based medicine era, available data from large
trials show that only beta-blockers and ACE inhibitors,
amongst the several antihypertensive drug classes, convincingly save lives in long-term post-myocardial infarction. Amongst the calcium antagonists, only verapamil
and perhaps diltiazem may be used as an alternative if
no significant left ventricular dysfunction is present.
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