Læknablaðið : fylgirit - 01.06.1994, Blaðsíða 14

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LÆKNABLAÐIÐ/FYLGIRIT 25
death from progressive heart failure. There were
also substantial cost reductions seen in reduced
need for further hospitalisation.
These studies began at variable times after the
ischaemic damage, ranging from months or years
in the SOLVD (4,5) studies, to 3 - 16 days after
acute MI on the SAVE study (3), down to slightly
earlier (2-7 days) in the AIRE study (6).
However it is now clear that ventricular dilata-
tion begins very early in the course of acute myo-
cardial infarction (AMI), so it was logical to try
ACE inhibition in the early phase of AMI, de-
spite concern that this might precipitate damag-
ing falls in blood pressure (BP).
CONSENSUS-2
This Scandinavian trial randomised about
6,000 patients to receive intravenous enalapril,
followed by oral enalapril, or placebos (7). It was
planned with a study size of 9,000 patients but was
stopped early on the advice of the data monitor-
ing committee who feared that the enalapril was
causing harm from hypotension. Later analysis
refuted this, but there was certainly little encou-
raging data in this trial.
Some smaller trials have also addressed the
question of ACE inhibition in the acute phase of
AMI and have been recently reported at scientific
meetings.
The CATS study (captopril and thrombolysis
study) (8) reported at the 2nd Intemational Sym-
posium on Heart Failure, Geneva 1993. 298 pa-
tients with a first anterior MI, treated with strep-
tokinase, were randomised to captopril or place-
bo at the end of the lytic infusion. A titration was
carried out after a 6.25 mgs captopril test dose. At
3 months there was a non significant trend to-
wards smaller L. V. volumes with captopril. Heart
failure was reported significantly less commonly
(24% placebo v 15% captopril, p = < 0.05).
The CAPTIN study (captopril in acute myocar-
dial infarction) (9) was reported at the XVth Eu-
ropean Society of Cardiology Congress at Nice
September 1993. 262 patients receiving tPA were
randomised to captopril or placebo. In this study
intravenous captopril 2 mgs and 4 mgs (within 30
and 45 mins respectively of the start of tPA in-
fusion), followed by oral captopril for 3 months.
There were no differences in mortality, reinfarc-
tion or need for revascularisation. On follow up at
3 days, 1 and 3 months there was progressive and
significant ventricular dilation only in the placebo
group.
In both studies (CATS and CAPTIN) hypoten-
sion was significantly more frequent in the ACE
inhibitor group, but was well tolerated.
ISIS-4
The ISIS-4 study was reported at the Novem-
ber 1993 meeting of the American Heart Associ-
ation in Atlanta. 58,000 patients were rando-
mised in a 2x2x2 factorial design to 24hour in-
travenous magnesium (80M.cq. MgSo4 or open)
control, a slow release oral nitrate (imdur 30mg,
then 60mg daily), or placebo for 1 month, and oral
captopril (6.25 mgs titrated rapidly to 50mgs bd),
or placebo for 1 month (10).
Trial inclusion criteria consisted of patients
seen within 24hours of a suspected AMI, whether
or not thrombolytics were given; short term oral
or intravenous non trial nitrate use was allowed,
and recorded. Cardiogenic shock or severe hypo-
tension were exclusion criteria, as was the wish of
the responsible physician to use or avoid one of
the trial treatments.
There were no interactions seen between the
treatments so ISIS-4 can be regarded as 3 sep-
arate trials of 29,000 v 29,000 patients in each
comparison.
Contrary to previous small trials there was no
significant effect on 5 week or longer term mortal-
ity from magnesium or nitrate (non significantly
beneficial for the nitrate; non significantly harm-
ful for magnesium).
Captopril significantly reduced 5 week and 6
month mortality (p = 0.02). The effect was mod-
est (about 5 less deaths/1000 patients) receiving
the active captopril. This effect was greater
(about 10-11/1000 fewer deaths) in patients with
larger infarcts, anterior MI, prior infarction or
heart failure.
Thus captopril was safe and reduced mortality
when started on the first day of an AMI, provided
patients with shock or severe hypotension
(SBP<90-100mmHg) were avoided, and the cap-
topril titrated cautiously. These favourable re-
sults were also seen in the Chinese captopril trial
results and in GISSI-3 (with lisinopril).
Heimildir fást hjá ritstjórn.