Myocardial infarction: thrombolysis given by bolus rather than by infusion increases intracranial haemorrhage without reducing death or reinfarction

Clinical bottom line (level 1a)

  1. Patients with an acute coronary syndrome and ST elevation who received thrombolysis as a bolus compared with an infusion are more likely to have an intracranial haemorrhage (NNH = 660 at 30 days).
  2. There is no clear difference in subsequent mortality or reinfarction between the two groups.
Mehta et al: Lancet 2000; 356 : 449-454
Expires February 2004

The study

Systematic review of all randomised trials of
  • Patients: acute coronary syndrome with ST elevation
  • Intervention: thrombolytic therapy given as a bolus (single or double over no more than 5 minutes) compared with thrombolytic therapy given as an infusion over at least 30 minutes
  • Outcome: death, intracranial haemorrhage, reinfarction
Articles found in ?all languages using Medline, Cochrane database of clinical trials, 1980 to 1999 (search terms: thrombolytic therapy, acute myocardial infarction, alteplase, duteplase, reteplase, lanoteplase, tenecteplase, saruplase, streptokinase, urokinase, anistreplase ) and and searching reference lists of review articles, and published abstracts from Scientrif SEssions of the American Heart Association, American College of Cardiology, and European Society of Cardiology from January 1994 to November 1999

Selection criteria: see above: by 2 independent reviewers - disagreements were resolved by discussion
Appraisal criteria: randomisation
Articles excluded if:
  • studies involving < 1000 patients
  • uncontrolled studies
  • dose-ranging studies based on angiographic or other non-clinical outcomes

7 studies involving 103972 patients
Studies were not found to be heterogeneous.

The evidence

Outcome Time to outcome CER OR
(95% CI)		 NNH
(95% CI)
bolus v. infusion: intracranial haemorrhage 30 days 324/53414
(0.61%)		 1.25
(1.08 to 1.45) 		660
(370 to 2100)
death 30 days 4711/53747
(8.77%)		 1.01
(0.97 to 1.06) 		1300
(NNT = 420 to infinity;
NNH = 210 to infinity)
reinfarction 30 days 1990/53414
(3.73%)		 1.04
(0.97 to 1.11) 		2800
(NNT = 930 to infinity;
NNH = 470 to infinity)

Comments

 

  1. No difference in non-haemorrhagic stroke was noted between the two groups.

Citation

  1. Mehta SR, EikelboomJW , Yusuf S: risk of intracranial haemorrhage with bolus versus infusion thrombolytic therapy: a meta-analysis. Lancet 2000; 356 : 449-454
Search Terms: from ACP Journal Club other articles noted
Contributor: Chris Ball, February 2002
Reviewer:

Clinical Question.
Patient acute coronary syndrome with ST elevation
Intervention or Exposure bolus thrombolysis
Comparison infusion thrombolysis
Outcome intracranial haemorrhage, death, myocardial infarction