Myocardial infarction: heparin did not reduce mortality.

Clinical bottom line (level 1b)

  1. Patients with acute myocardial infarction who were given heparin had no clear difference in combined end point (death and heart failure), than those not given heparin.
  2. Patients who were given heparin were more likely to have major adverse events, than those not given heparin.
Gruppo Italiano Per Lo Studio Della Sopravvienza Nell' Infarcto Miocardico : Lancet 1990; 336: 65-71
Expires December 2004

The study

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

12490 patients (aged ?, 70% male) Chest pain accompanied by ST segment elevation of 1 mm or more in any limb lead of the ECG and/or 2 mm or more in any precordial lead, and if they were admitted to the coronary care unit within 6 hours of symptom onset

Excluded if
  • surgical procedure or invasive procedure or trauma within the previous two weeks
  • recent or current bleeding
  • cerebrovascular accident within previous 6 months
  • uncontrolled hypertension (systolic > or = 200 mmHg or diastolic > or = 110 mmHg)
  • previous treatment with streptokinase (within past 6 months)


Control Group: (n = 6206, 6206 analysed): no heparin
Experimental Group: (n = 6175, 6175 analysed): heparin 12, 500 U subcutaneously twice daily starting 12 hours after the beginning of streptokinase or tissue plasminogen activator infusion and continued until discharge
Recommended treatment for all patients was oral aspirin (300-325 mg/day) and atenolol (5-10 mg given by slow iv injection according to the ISIS-1 criteria as soon as MI diagnosed).
99.1% followed for ? weeks
Outcome notes:

  • combined end point : death plus those with late (beyond day 4 of hospitalisation) congestive heart failure or extensive left ventricular damage in the absence of clinical heart failure
  • major adverse events : stroke, total bleeds and pulmonary and systemic thromboembolism

The evidence

Outcome Time to outcome CEREERRRR
(95% CI)		ARR
(95% CI)		NNT
(95% CI)
combined end point unknown 1419
(22.9%)		 1403
(22.7%)		 1.00%
(-6.00% to 7.00%)		 0.14%
(-1.33% to 1.62%)		 693
(NNT = 62 to infinity;
NNH = 75 to infinity)
major adverse events unknown 480
(7.73%)		 744
(12.1%)		 -56.0%
(-74.0% to -40.0%)		 -4.31%
(-5.36% to -3.26%)		 -23
(-31 to -19)

Comments

  1. Patients were also randomised to either tissue plasminogen activator or streptokinase as another part of the trial. (See GISSI2_90)
  2. Although the study is too small to demonstrate a detrimental effect of heparin, there is little chance of a significant reduction in mortality. This is validated in various systematic reviews and meta-analyses.

Citation

  1. Gruppo Italiano Per Lo Studio Della Sopravvienza Nell' Infarcto Miocardico , : GISSI-2: A factorial randomised trial of alteplase versus streptokinase and heparin versus no heparin among 12 490 patients with acute myocardial infarction. Lancet 1990; 336: 65-71
Contributor: Clare Wotton and Bob Phillips, December 1999
Reviewer:

Clinical Question.
Patient acute myocardial infarction
Intervention or Exposure heparin
Comparison no heparin
Outcome mortality