Stroke: clopidogrel decreased any stroke, MI or death compared with aspirin.

Clinical bottom line (level 1b)

  1. Patients at risk from ischaemic events who were given clopidogrel were less likely to suffer any stroke, MI or death, than those given aspirin (NNT = 197 at 1.90 years) .
  2. There was no clear difference in combined MI, stroke and fatal events.
CAPRIE Steering Committee : Lancet 1996; 348: 1329-1339
Expires November 2004

The study

Double-blinded ?concealed randomised trial with intention-to-treat
Setting: 384 clinical centres from 16 countries

19185 patients (aged mean 63 years, 72% male) recent ischaemic stroke (> or = 1 week and < or = 6 months before randomisation), recent MI < or = 35 days before randomisation) or peripheral arterial disease

Excluded if
  • age <21 years
  • severe cerebral deficit likely to lead to patient being bedridden or demented
  • carotid endarterectomy after qualifying stroke
  • qualifying stroke induced by carotid endarterectomy or angiography
  • unlikely to be discharged aline after qualifying event
  • severe co-morbidity likely to limit life expectancy to <3 years
  • uncontrolled hypertension
  • contraindications to study drugs
  • women of childbearing age not using reliable contraception
  • currently receiving study drug
  • previously entered in other clopidogrel studies
  • geographic or other factors making study participation impractical


Note:
  • 95% of patients were white.
  • Patients were given a list of common over-the-counter aspirin-containing products and were instructed to avoid them.
  • The study was double-blind, but in case of emergency, there was a sealed treatment code label on the initial supply of the drug which could not be resealed once broken. The code was broken 21 times during the course of the study (11 in the clopidogrel and 10 in the aspirin group).


Control Group: (n = 9586, 9586 analysed): aspirin one 325 mg tablet per day
Experimental Group: (n = 9599, 9599 analysed): clopidogrel one 75 mg tablet per day
Both groups received placebos of the other study drug.
99.7% followed for 1.9 years mean, range 1-3 years
Outcome notes:
  • any stroke, MI or death : fatal and non-fatal events included

The evidence

Outcome Time to outcome CEREERRRR
(95% CI)		NNT
(95% CI)
primary outcome cluster (ischaemic stroke, MI, vascular death) 1.90 years 571
(5.96%)		 560
(5.83%)		 8.7%
(0.3% to 16.5%)		 197
(104 to 5720)
any stroke, MI or death 1.90 years 1447
(15.09%)		 1353
(14.1%)		 7.0%
(-0.9% to 14.2%)		 207
(NNT = 102 to infinity;
NNH = 1610 to infinity)

  • There were 3847 adverse effects reported in the clopidogrel group and 3944 in the aspirin group.
  • Compliance of tablet taking was assessed by counting returned tablets. Compliance at the end of the study was 91%.

Comments

  1. The major niche for this (expensive) product is in treating patients who are intolerant of aspirin.
  2. This trial does not give any evidence for use of clopidogrel in treating 'aspirin failures' - patients who have suffered a recurrent vascular event whilst on aspirin treatment.

Citation

  1. CAPRIE Steering Committee , : A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996; 348: 1329-1339
Contributor: Clare Wotton and Musab Hayatli, November 1999
Reviewer: RH Harwood

Clinical Question.
Patient at risk of ischaemic events
Intervention or Exposure clopidogrel
Comparison aspirin
Outcome ischaemia stroke, MI or death