Myocardial infarction: increased age, female sex, lighter weight, African ancestry and type of thrombolytic therapy affected bleeding.

Clinical bottom line (level 2b)

  1. A sixth of patients who had thrombolytic therapy after myocardial infarction will had a moderate or severe bleed.
  2. Patients who had thrombolytic therapy after a myocardial infarction were at an increased risk of a moderate or severe bleed if they: were female, of African ancestry, older age, or treated outside the US.
  3. Patients who had thrombolytic therapy after a myocardial infarction were at a decreased risk of bleeding if they have a higher diastolic blood pressure (90 vs 80 mmHg), were US patients treated with tissue plasminogen activator vs streptokinase plus subcutaneous heparin or are were lighter weight.
Berkowitz et al: Circulation 1997; 95: 2508-2516
Expires March 2003

The study

Prospective cohort study with objective outcomes, adjusted for confounding factors, not validated in an independent set of patients.

Setting: multicentre, USA

40903 patients (aged range 52 to 70 years; mean 62, 75% male) chest pain lasting > or = 20 minutes and accompanied by ECG signs of > or = 0.1 mV of ST segment elevation in two or more leads

Excluded if
  • not presenting within 6 hours of symptom onset
  • active bleeding
  • recent trauma or major surgery
  • history of stroke
  • noncompressible vascular punctures
  • previous treatment with streptokinase or anistreplase



Factors studied:
  • moderate or severe bleeding, age, race, biophysical characteristics, enrolment, smoking, hypertension, hypercholesterolaemia, heart failure
  • female
  • African ancestry (vs White patients as control group)
  • age (60 vs 50 years) : using overall rate as control
  • treated in the US
  • US patients treated with streptokinase plus IV heparin vs streptokinase plus subcutaneous heparin
  • non-US patients treated with streptokinase plus IV heparin vs streptokinase plus subcutaneous heparin
  • non-US patients treated with a combination vs streptokinase plus subcutaneous heparin
  • US patients treated with tissue plasminogen activator vs streptokinase plus subcutaneous heparin
  • blood pressure (90 vs 80 mmHg diastolic)
  • weight (100 vs 90 kg)
  • weight (85 vs 75 kg)


Patients were randomly assigned to one of four thrombolytic strategies: streptokinase 1.5 million U over 60 minutes plus subcutaneous heparin 12, 500 IU twice daily; streptokinase 1.5 million U over 60 minutes plus intravenous heparin bolus of 5000 U followed by 1000 U/h; accelerated tissue plasminogen activator bolus of 15 mg immediately followed by infusion 0.75 mg/kg over 30 minutes and then 0.5 mg/kg over the next 60 minutes, plus intravenous heparin; combination of intravenous tissue plasminogen activator plus streptokinase, plus intravenous heparin.

Multivariate analysis was used to adjust for confounding factors.

100% followed for 30 days
Outcomes studied:
  • moderate or severe bleeding severe bleeding was defined substantial haemodynamic compromise that required intervention or treatment and moderate if transfusion was required but did not lead to haemodynamic compromise requiring intervention.

The evidence

outcome time to outcome number of patients/total number %
(95% CI)
moderate or severe bleeding 30 days 5388/40903 13.2%
(12.8% to 13.5%)

prognostic factor for
moderate or severe bleeding 		time to outcome control rate (%) adjusted OR
(95% CI)		 NNF+
(95% CI)
female 30 days 3176/40903
(7.76%) 		1.42
(1.31 to 1.53) 		34
(27 to 46)
African ancestry 30 days 4957/39748
(12.5%) 		1.33
(1.12 to 1.57) 		29
(17 to 77)
age (60 vs 50 years) 30 days /
(13.2%) 		1.30
(1.26 to 1.35) 		30
(26 to 35)
treated in the US 30 days 1965/17862
(11.0%) 		1.76
(1.08 to 2.85) 		15
(7 to 171)
US patients treated with streptokinase plus IV heparin vs streptokinase plus subcutaneous heparin 30 days /
(13.2%) 		1.13
(1.01 to 1.26) 		68
(35 to 874)
non-US patients treated with streptokinase plus IV heparin vs streptokinase plus subcutaneous heparin 30 days /
(13.2%) 		1.63
(1.36 to 1.95) 		15
(10 to 25)
non-US patients treated with a combination vs streptokinase plus subcutaneous heparin 30 days /
(13.2%) 		1.66
(1.39 to 1.99) 		14
(10 to 24)
US patients treated with tissue plasminogen activator vs streptokinase plus subcutaneous heparin 30 days /
(13.2%) 		0.85
(0.76 to 0.96) 		57
(35 to 173)
blood pressure (90 vs 80 mmHg diastolic) 30 days /
(13.2%) 		0.94
(0.92 to 0.96) 		144
(104 to 217)
weight (100 vs 90 kg) 30 days /
(13.2%) 		0.83
(0.73 to 0.95) 		50
(31 to 173)
weight (85 vs 75 kg) 30 days /
(13.2%) 		0.81
(0.78 to 0.85) 		45
(39 to 57)

Citation

  1. Berkowitz SD, Granger CB, Pieper KS, et al: Incidence and predictors of bleeding after contemporary thrombolytic therapy for myocardial infarction. Circulation 1997; 95: 2508-2516
Contributor: Clare Wotton and Bob Phillips, January 2000
Reviewer:

Clinical Question.
Patient thrombolytic therapy for myocardial infarction
Intervention or Exposure presence of risk factors
Comparison absence of risk factors
Outcome bleeding