Myocardial infarction: lisinopril, with or without glyceryl trinitrate decreased mortality.

Clinical bottom line (level 1b)

  1. Patients with myocardial infarction who were given lisinopril were less likely to die, than those given a control (NNT = 127 at 6 weeks) .
  2. Patients given lisinopril plus nitrates were less likely to die, than those given a control (NNT = 85 at 6 weeks) .
  3. There was no clear difference in mortality between patients given nitrates and control.
Gruppo Italiano per lo Studio della Soprawivenza nell'Inarto Miocardico : Lancet 1994; 343: 1115-1122
Expires January 2004

The study

Unblinded concealed randomised trial with intention-to-treat
Setting: multicentre, Italy

19394 patients (aged 27% aged >70 years, 78% male) chest pain accompanied by elevation or depression of the ST-segment of at least 1 mm in one or more peripheral leads of the ECG, or at least 2 mm in one or more precordial leads

Excluded if
  • not admitted within 24 hours of symptom onset
  • contraindications to study treatments
  • severe heart failure requiring any of the study treatments
  • Killip class 4
  • high risk of severe further haemodynamic deterioration after treatment with vasodilators (systolic blood pressure 100 mmHg or less)
  • documented allergy to a study drug
  • other life-threatening disorders
  • previous randomisation in the study


    • Control Group: (n = 9460, 9460 analysed): open control
    Experimental Group: (n = 9435, 9435 analysed): oral lisinopril (5mg at randomisation, 5 mg after 24 hours, 10 mg after 48 hours, then 10 mg daily for 6 weeks)
    Experimental Group: (n = 9453, 9453 analysed): transdermal glyceryl trinitrate (iv for first 24 hours at 5 µ g/min and rising by 5-20 µ g/min every 5 minutes for the first 30 minutes until systolic blood pressure fell by at least 10%, provided it stayed above 90 mmHg. After 24 hours, a patch provided 10 mg daily transdermally- it was removed at night to give a 10 hour period without nitrates)
    Experimental Group: (n = 4722, 4722 analysed): both lisinopril and glyceryl trinitrate
    Patients also received thrombolytics, beta-blockers and aspirin as required.
    97.4% followed for 6 weeks

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    mortality- lisinopril vs control 6 weeks 673
    (7.11%)    		 597
    (6.33%)    		 11%
    (1% to 20%)    		 0.79%
    (0.07% to 1.50%)    		 127
    (67 to 1375)
    mortality- nitrates vs control 6 weeks 653
    (6.92%)    		 617
    (6.53%)    		 6%
    (-5% to 15%)    		 0.39%
    (-0.33% to 1.10%)    		 257
    (NNT = 91 to infinity;
    NNH = 308 to infinity)
    mortality- lisinopril plus nitrates vs control 6 weeks 341
    (7.21%)    		 285
    (6.04%)    		 16%
    (3% to 28%)    		 1.18%
    (0.17% to 2.18%)    		 85
    (46 to 579)

    Comments

    1. There were only 9442 controls compared to those taking glyceryl trinitrate. The number of controls was also different when compared with lisinopril plus nitrates.
    2. Patients were randomised for each study treatment separately.

    Citation

    1. Gruppo Italiano per lo Studio della Soprawivenza nell'Inarto Miocardico , : GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Lancet 1994; 343: 1115-1122
    Contributor: Clare Wotton and Bob Phillips, January 2000
    Reviewer:

    Clinical Question.
    Patient myocardial infarction
    Intervention or Exposure lisinopril or glycerol trinitrate
    Comparison open control
    Outcome mortality