New Zealand Data Sheet
Lisinopril (Teva)
Lisinopril Tablets 5 mg, 10 mg, 20 mg
Version 1.1 4
Acute Myocardial Infarction
Treatment with lisinopril may be started within 24 hours of the onset of symptoms. The first
dose of lisinopril is 5 mg given orally, followed by 5 mg after 24 hours, 10 mg after 48 hours
and then 10 mg once daily thereafter. Patients with a low systolic blood pressure (120 mm Hg
or less) when treatment is started or during the first 3 days after the infarct should be given a
lower dose - 2.5 mg orally (see Warnings and Precautions). If hypotension occurs (systolic
blood pressure less than or equal to 100mm Hg) a daily maintenance dose of 5 mg may be
given with temporary reductions to 2.5 mg if needed. If prolonged hypotension occurs
(systolic blood pressure less than 90mm Hg for more than 1 hour) lisinopril should be
withdrawn. Dosing for patients with acute myocardial infarction should continue for six
weeks. (For patients who develop symptoms of heart failure, see Dosage and
Administration, Congestive Heart Failure).
Lisinopril is compatible with intravenous or transdermal glyceryl trinitrate.
Lisinopril is indicated in the management of patients with acute myocardial infarction to
prevent the subsequent development of left ventricular dysfunction (as defined by an ejection
fraction less than or equal to 35%) or heart failure and to improve survival, based on the
outcome of the Gruppo Italiano per lo Studio della Sporavvienza nell'Infarto Miocardico
(GISSI-3) trial. The GISSI-3 study was a multicentre, controlled, randomised, unblinded
clinical trial conducted in 19,394 patients with acute myocardial infarction admitted to a
coronary care unit. It was designed to examine the effects of short-term (six week) treatment
with lisinopril, nitrates, their combination, or no therapy on short-term (six week) mortality
and on longer-term death and markedly impaired cardiac function. Patients presenting within
24 hours of the onset of symptoms who were haemodynamically stable were randomised, in a
2 x 2 factorial design, to six weeks of either lisinopril alone (n = 4,841), nitrates alone (n =
4,869), lisinopril plus nitrates (n = 4,841) or open control (n = 4,843). All patients received
routine therapies, including thrombolytics (72%), aspirin (84%) and a beta-blocker (31%), as
appropriate, normally utilised in acute myocardial infarction (MI) patients.
The protocol excluded patients with hypotension (systolic blood pressure less than or equal to
100 mmHg), severe heart failure, cardiogenic shock, and renal dysfunction (serum creatinine
> 2 mg/dL and/or proteinuria > 500 mg/24 hours). Doses of lisinopril were adjusted as
necessary according to protocol (see Dosage and Administration).
Study treatment was withdrawn at six weeks except where clinical conditions indicated
continuation of treatment.
The primary outcomes of the trial were the overall mortality at six weeks and a combined
endpoint at six months after the myocardial infarction, consisting of a number of patients who
died, had late (day 4) clinical congestive heart failure, or had extensive left ventricular
damage defined as ejection fraction less than or equal to 35% or an akinetic-dyskinetic (A-D)
score greater than or equal to 45%. Patients receiving lisinopril (n = 9,646), alone or with
nitrates, had an 11% lower risk of death at six weeks (2p (two tailed) = 0.04) compared to
patients receiving no lisinopril (n = 9,672) (6.4 versus 7.2%, respectively). The reduction in
mortality at six months was not significant, but this was not a primary outcome measure.
Although patients randomised to receive lisinopril for up to six weeks also fared numerically
better on the combined endpoint at six months, the open nature of the assessment of heart
failure, substantial loss to follow-up echocardiography, and substantial excess use of lisinopril
between six weeks and six months in the group randomised to six weeks of lisinopril,
preclude any conclusion about this endpoint.
Patients with acute myocardial infarction treated with lisinopril had a higher (9.0 versus
3.7%) incidence of persistent hypotension (systolic blood pressure < 90 mmHg for more than