Fortnightly review: Secondary prevention in acute myocardial infarctionBMJ 1998; 316 doi: https://doi.org/10.1136/bmj.316.7134.838 (Published 14 March 1998) Cite this as: BMJ 1998;316:838
All rapid responses
Following the earlier overview of secondary prevention in survivors
of myocardial infarction (1) and correspondence which followed (2), we
would like to present a viewpoint which we believe is in line with the
clinical trial data to hand, clinical practice needs and ongoing trials in
Firstly, with respect to ACE inhibition post MI. There is a small
benefit that can be achieved from treating all patients, as evidenced from
the ISIS-4 (3) and GISSI-3 (4) studies. A greater benefit is provided
through a selective high risk approach in patients with LV dysfunction or
heart failure post MI, as evidenced from the SAVE (5) and AIRE (6)
studies. Thus, there are optional evidence-based approaches but general
agreement that ACE inhibition is a standard treatment requirement for
patients with LV dysfunction or heart failure post MI and that this
treatment should be given without undue delay.
With respect to beta blockers, there is clear evidence of benefit
from a number of trials in which a general treatment approach has been
taken post MI (7). However in these trials, patients with heart failure
were generally excluded and most were conducted in the pre-thrombolysis
and pre-ACE inhibitor era. Benefit from beta blockade post MI in heart
failure sub-groups has been suggested from retrospective subgroup analyses
of different kinds (8). Retrospective analysis of the SAVE study data has
also suggested that the benefit from beta blockade is additive to that of
ACE inhibition (9). Furthermore, a benefit from beta blocker treatment in
addition to standard ACE inhibitor treatment in patients with chronic
heart failure is now established.
The evidence gap that currently exists relates to the lack of
definitive randomised, controlled trial data in patients with post MI LV
dysfunction or heart failure, treated with beta blocker treatment in
addition to standard ACE inhibitor treatment. The mechanisms of benefit
from ACE inhibitor treatment on the one hand and beta blocker treatment on
the other may be similar in some respects, but clearly complementary in
others. ACE inhibitors appear to reduce deaths from progressive heart
failure but there is no clear sudden death benefit from such treatment.
Both ACE inhibitors and beta blockers can improve ventricular remodeling
but the main benefit from beta blocker treatment may be a reduction in
sudden and arrhythmic death. Furthermore, the new generation beta blocker
agents may be more effective than first generation drugs.
These considerations provide the rationale for trials currently in
progress, in which patients with post MI LV dysfunction or heart failure
established on standard ACE inhibitor treatment, are randomised to beta
blocker treatment or placebo as in the current international CAPRICORN
Study using carvedilol. No meta-analysis or retrospective sub group
analyses can replace the need for such definitive studies.
In the future, polypharmacy may be avoided by careful patient
assessment and treatment selection, combining clinical judgement and
evidence-application to optimise clinical outcomes. More evidence is
still required to allow most appropriate treatment selection. NNT
estimates for these high-risk post MI patients in general, are such that
cost effectiveness is not an issue.
Professor Norman Sharpe Dr Robert Doughty
HEAD, DEPARTMENT OF MEDICINE National Heart Foundation of New Zealand BNZ
1. Mehta RH, Eagle KA. Secondary prevention in acute myocardial
infarction. BMJ 1998; 316: 838-842 (14 March)
2. McAlister FA. Trial is needed of ACE inhibitors plus b blockers in
survivors of myocardial infarction (letter). BMJ 1998; 317: 751 (12
3. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative
Group. A randomised factorial trial assessing early oral captopril, oral
mononitrate and intravenous magnesium sulphate in 58,050 patients with
suspected acute myocardial infarction. Lancet 1995; 345: 669-685
4. GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate
singly and together on 6-week mortality and ventricular function after
acute myocardial infarction. Gruppo Italiano per lo Studio della
Sopravvivenza nell'Infarto Miocardio. Lancet 1994; 343: 1115-1122
5. Pfeffer MA, Braunwald E, Moye LA et al. Effect of captopril on
mortality and morbidity in patients with left ventricular dysfunction
after myocardial infarction - Results of the Survival and Ventricular
Enlargement Trial. N Engl J Med 1992; 327: 669-677.
6. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators.
Effect of ramipril on mortality and morbidity of survivors of acute
myocardial infarction with clinical evidence of heart failure. Lancet
1993; 342: 821-828
7. Yusuf S, Peto R, Lewis J, Collins R, Sleight P. Beta blockade during
and after myocardial infarction: An overview of the randomised trials.
Prog CV Dis 1985; 4: 335-371.
8. The Beta Blocker Pooling Project Research Group. The Beta Blocker
Pooling Project (BPPP): subgroup findings from randomised trials in post-
infarction patients. Eur Heart J 1998; 9:8-16
9. Vantrimpont P, Roulear JL, Wun CC et al. Additive beneficial effects
of beta blockers to angiotensin-converting enzyme inhibitors in the
Survival and Ventricular Enlargement Study (SAVE). J Am Coll Cardiol
1997; 29: 229-236
Competing interests: No competing interests