GISSI-1: Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico
Purpose
To determine whether streptokinase (SK) reduces mortality when given shortly after onset of acute MI, and whether benefit, if present, depends on interval from pain onset to SK treatment
Reference
Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico. Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986;i:397–402.
GISSI-1: Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico - TRIAL DESIGN -
Design
Multicenter, randomized, open, parallel group
Patients
11,806 patients with onset of acute MI within previous 12 h
Follow up and primary endpoint
Primary endpoint: all-cause mortality. 14–21 days follow up
Treatment
Patients randomized to treatment group (IV SK, 1.5 million U over 60 min) or control (no infusion)
GISSI-1: Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico - RESULTS -
21-day mortality significantly reduced in SK group (relative risk 0.81, P=0.0002) compared with control
For SK given at <6 h, the shorter the interval between pain onset and treatment, the bigger the reduction in mortality
For SK given at >6 h, no significant difference between treatment and control
SK judged safe in view of low incidence of adverse effects (major bleeds in 0.3% of SK group, anaphylactic shock in 0.1%)
GISSI-1: Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico - RESULTS continued -
Control
(n=5852)
P
Mortality and causes of death
GISSI. Lancet 1986; i:397–402.
SK
(n=5860)
Relative risk
(95% CI)
Mortality
%
No.
Causes of death
Cardiovascular
Noncardiovascular
Undefined
13.0
758
696
45
17
10.7
628
588
32
8
0.81 (0.72–0.90)
0.0002
GISSI-1: Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico - RESULTS continued -
Control, %
(deaths/n)
Hours from onset
to treatment
P
Mortality and time before treatment
GISSI. Lancet 1986; i:397–402.
SK, %
(deaths/n)
Relative risk
(95% CI)
<3*
>3
–
6
>6
–
9
>9
–
12
*<1
12.0
(369/3078)
14.1
(254/1800)
14.1
(93/659)
13.6
(41/302)
15.4
(99/642)
9.2
(278/3016)
11.7
(217/1849)
12.6
(87/693)
15.8
(46/292)
8.2
(52/635)
0.74 (0.63–0.87)
0.80 (0.66–0.98)
0.87 (0.64 –1.19)
1.19 (0.75–1.87)
0.49 (0.34–0.69)
0.0005
0.03
NS
NS
0.0001
GISSI-1: Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico - SUMMARY -
Given within 6 h of onset of pain in acute MI, intravenous SK:
Reduced mortality
Conferred greater benefit when administered earlier