CAPRIE: Clopidogrel versus Aspirin in Patients at risk of Ischemic Events

Purpose

To assess the relative efficacy of the antiplatelet drugs clopidogrel and aspirin in reducing the risk of thrombotic events in patients with atherosclerotic disease.

ReferenceCAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996;348:1329–39.

CAPRIE: Clopidogrel versus Aspirin in Patients at risk of Ischemic Events- TRIAL DESIGN -

DesignMulticenter, multinational, randomized, double-blind, parallel group

Patients19,185 patients with atherosclerotic vascular disease (either recent ischemic stroke, recent MI or symptomatic peripheral arterial disease)

Follow up and primary endpointPrimary combined endpoint: ischemic stroke, MI or vascular death. Mean 1.9 years follow up.

TreatmentAspirin 325 mg once daily or clopidogrel 75 mg once daily

CAPRIE: Clopidogrel versus Aspirin in Patients at risk of Ischemic Events- TRIAL DESIGN continued-

Stroke

MI

Peripheral arterial disease

Patient subgroups

33.4%

32.9%

33.7%

Aspirin(n=9586)

33.7%

32.7%

33.6%

Clopidogrel(n=9599)

CAPRIE Steering Committee. Lancet 1996;348:1329–39.

CAPRIE: Clopidogrel versus Aspirin in Patients at risk of Ischemic Events- RESULTS -

• Annual event rate for primary endpoint of ischemic stroke, MI or vascular death significantly reduced in clopidogrel group compared with aspirin (5.32 vs. 5.83%, p<0.043)

• Effect of clopidogrel compared with aspirin indicated that benefit may not be identical between subgroups (p=0.042 for test of heterogeneity):

— reduction in event rate was significant in patients with existing peripheral arterial disease

— reduction in the group with previous stroke, though not significant

— increased event rate in the group with previous MI, though not significant

• Clopidogrel was well tolerated as defined by withdrawal rate from trial: only marginally higher vs aspirin (21.3 vs. 21.1%)

CAPRIE: Clopidogrel versus Aspirin in Patients at risk of Ischemic Events- RESULTS continued -

Months after randomization

Cumulativerisk (%)

00

6 12 18 24 30 36

5

10

15

20

CAPRIE Steering Committee. Lancet 1996;348:1329–39.

Aspirin

Clopidogrelp=0.043

Primary endpoint: stroke, MI or vascular death

CAPRIE: Clopidogrel versus Aspirin in Patients at risk of Ischemic Events- RESULTS continued -

Stroke Clopidogrel (6054)Aspirin (5979)

MI Clopidogrel (5787)Aspirin (5843)

Peripheral arterialdisease

Clopidogrel (5795)Aspirin (5797)

All patients Clopidogrel (17,636)Aspirin (17,519)

7.157.71

5.034.84

3.714.86

5.325.83

0.26

0.66

0.0028

0.043

Relative risk reduction (%)

7.3%(–5.7 to 18.7)

–3.7%(–22.1 to 12.0)

23.8%(8.9 to 36.2)

8.7%(0.3 to 16.5)

SubgroupTreatment group(patient years at risk)

Eventsper year(%)

pRelative riskreduction (95% CI)

Primary endpoint by subgroup

Aspirinbetter

Clopidogrelbetter

0–10–20 10 20 30 40–30

CAPRIE Steering Committee. Lancet 1996;348 :1329–39.

CAPRIE: Clopidogrel versus Aspirin in Patients at risk of Ischemic Events- RESULTS continued-

Patient years at risk

Stroke and MI

17,519

Aspirin

17,636

MI

Nonfatal

Fatal

270

63

226

49

Clopidogrel

CAPRIE Steering Committee. Lancet 1996;348:1329–39.

Stroke

Nonfatal

Fatal

430

32

405

33

CAPRIE: Clopidogrel versus Aspirin in Patients at risk of Ischemic Events- SUMMARY -

Compared with aspirin, in patients with atherosclerotic vascular disease, clopidogrel:

• Reduced the primary combined endpoint of stroke, MI or vascular death in the total study population

• Conferred benefit in peripheral arterial disease and stroke subgroups

• Conferred no significant benefit in previous MI subgroup

CAPRIE: Clopidogrel versus Aspirin in Patients at risk of Ischemic Events- SUMMARY -

Compared with aspirin, in patients with atherosclerotic vascular disease, clopidogrel:

• Reduced the primary combined endpoint of stroke, MI or vascular death in the total study population

• Conferred benefit in peripheral arterial disease subgroup• Conferred no significant change in risk in stroke and MI

subgroups