Stroke: higher doses of LMWH were not clearly better than lower ones.

Clinical bottom line (level 1b-)

  1. Patients with a recent stroke who received high-dose certoparin compared with 3000 units once daily were not clearly more likely to have a good functional outcome, die or have a major haemorrhage.
Diener et al: Stroke 2001; 32 : 22-29
Expires November 2003

The study

Double-blinded ?concealed randomised trial with intention-to-treat
Setting: 8 acute hospitals, Germany

404 patients (aged mean 67, 53% male) with an acute ischaemic stroke with moderate to severe paresis of an arm or leg or both (confirmed on CT within 12 hours)

Excluded if
  • pregnancy or breast-feeding
  • known allergy or hypersensitivity to heparins
  • unstable neurological deficit
  • acute or unstable cardiovascular disease
  • hypertension (> 220/120 mmHg) or hypotension ( < 90/60 mmHg)
  • major illnesses: active, recurrent or metastatic cancer, severe hepatic or renal disease
  • known thrombocytopenia or coagulopathy within last month
  • severe diabetic retinopathy
  • evidence of haemorrhage or structural brain injury on CT
  • aged < 18, > 85
  • no CT confirmation

Note:
  • Patients were stratified for stroke territory before randomisation.

    Control Group: (n = 99, 96 analysed): certoparin 3000 U once daily
    Experimental Group: (n = 102, 97 analysed): certoparin 3000 U twice daily
    Experimental Group: (n = 103, 98 analysed): certoparin 5000 U twice daily
    Experimental Group: (n = 100, 96 analysed): certoparin 8000 U twice daily

    96% followed for 3 months

    The evidence

    higher dose v. certoparin 3000 U once daily
    Outcome Time to outcome CER EER RRR
    (95% CI)    		 ARR
    (95% CI)    		 NNT
    (95% CI)
    death 3 months 4
    (4.04%)    		 26
    (8.52%)    		 -111%
    (-490% to 25%)    		 -4.48%
    (-9.47% to 0.50%)    		 -22
    (NNT = 120 to infinity;
    NNH = 11 to infinity)
    good functional outcome 3 months 59
    (59.6%)    		 175
    (57.4%)    		 4%
    (-16% to 20%)    		 2.22%
    (-8.93% to 13.4%)    		 45
    (NNT = 7 to infinity;
    NNH = 11 to infinity)
    major haemorrhage 3 months 3
    (3.03%)    		 12
    (3.93%)    		 -30%
    (-350% to 63%)    		 -0.90%
    (-4.92% to 3.12%)    		 -110
    (NNT = 32 to infinity;
    NNH = 20 to infinity)

    Comments

    1. No individual dose was clearly better than another.
    2. The study was too small to show a difference between the groups, but showed a tendency for increased bleeding at higher doses.

    Citation

    1. Diener HC, Ringelstein EB, von Kummer R, et al: treatment of acute ischemic stroke with the low-molecular-weight heparin certoparin: results of TOPAS trial. Stroke 2001; 32 : 22-29
    Search Terms: from ACP Journal Club other articles noted
    Contributor: Chris Ball, November 2001
    Reviewer:

    Clinical Question.
    Patient
    Intervention or Exposure
    Outcome