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Clopidogrel vs. Aspirin in Patients at Risk of Ischemic Events (CAPRIE)
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| Patients (n): |
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19,185 |
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| Qualifying event (n): |
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Stroke (6,432).Myocardial infarction (6,302).PAD (6,452) |
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| Mean follow-up time: |
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1.91 years |
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| Primary endpoint combined endpoint of: |
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Ischemic stroke, MI, vascular death |
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| Study treatment (dose): |
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Clopidogrel (75 mg/day) Aspirin (325 mg/day) |
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| Adverse events: |
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Rash, diarrhea, indigestion/nausea/vomiting, any bleeding disorder,
intracranial hemorrhage, gastrointestinal hemorrhage, abnormal liver function
Thrombotic thrombocytopenic purpura (TTP), 3.7 persons/year/1 million, 11 cases with clopidogrel
ASA = Acetylsalicylic Acid
PAD = Peripheral Arterial Disease |
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Reference:
CAPRIE Steering Committee. Lancet 1996; 339: 1329-1339..Bennett et al. N Engl J Med 2000; 342: 1773-1777.
The efficacy of clopidogrel and aspirin was compared in the Clopidogrel versus Aspirin Patients at
Risk of Ischemic Events (CAPRIE) study. The qualifying event in the CAPRIE study differs from other trials: the study
population comprised patients with atherosclerotic vascular disease. The patients were distributed evenly over 3
subgroups according to their qualifying event: ischemic stroke, myocardial infarction or peripheral arterial
disease (PAD). For this reason, a composite outcome event of non-fatal ischemic stroke, non-fatal myocardial
infarction, or vascular death was chosen.
Both aspirin and ticlopidine have been shown to be of benefit in placebo-controlled studies. Clopidogrel is a new
thienopyridine derivative, chemically related to ticlopidine. Clopidogrel prevents arterial as well as venous
thrombosis and reduces atherogenesis in several animal species.
 
CAPRIE Results by Subgroup Analysis in the Combined Endpoint
Reference:
CAPRIE Steering Committee. Lancet 1996; 339: 1329-1339.
The intention-to-treat analysis of the primary outcome cluster showed an overall relative risk
reduction of 8.7% (P = 0.043), with 95% CI of 0.3-16.5. When the corresponding subgroup analyses were carried out
separately for the ischemic stroke, myocardial infarction, and peripheral arterial disease subgroups, the
estimated relative risk reductions were 7.3%, -3.7%, and 23.8%, respectively. A test for heterogeneity was
significant (P = 0.042), suggesting that the true benefit may not be identical across the 3 clinical subgroups.
From these observed treatment effects, the possibility cannot be ruled out entirely that clopidogrel and aspirin are
only equivalent in benefit in patients presenting with myocardial infarction, or that the benefit of clopidogrel over
aspirin is truly much greater in patients with peripheral arterial disease.
Stroke Prevention Therapy.
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Clopidogrel
vs. aspirin 325 mg/day in
stroke patients
(CAPRIE; 1.91 years data)¹ |
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ASA/ER-DP
vs. aspirin 50 mg/day in
patients with stroke or TIA
(ESPS2; 2 years data)² |
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| RRR (stroke and post-stroke patients) |
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| 8.0% (P = .28)* |
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23.1% (P = .006)² |
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| Strokes prevented per 1,000 patients |
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| 8¹ |
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30² |
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| NNT to prevent one stroke |
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| 1214 |
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344 |
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*In a post hoc analysis.³
References:
¹ CAPRIE Steering Committee. Lancet 1996; 348: 1329-1339.
² Diener et al. J Neurol Sci 1996; 143: 1-13.
³ Albers et al. Chest 2001; 115 (Suppl): 300-320.
4 Data on file. Boehringer Ingelheim Pharmaceuticals, Inc.
The relative risk reduction for the endpoint of stroke with clopidogrel vs. aspirin was 8% in a post
hoc analysis, as compared to 23.1% with ASA/ER-DP vs. Aspirin. For the combined endpoint of stroke, MI, and vascular
death, the relative risk reduction was 7.3%.
Clopidogrel in Unstable Angina to Prevent Recurrent Ischaemic Events (CURE)
- 12,562 patients enrolled with acute coronary syndromes
- Clopidogrel (300 mg loading, then 75 mg qd) + ASA (75-325 mg qd) vs. ASA (75-325 mg qd) + placebo for 3-12 months
- Primary endpoint = (CV death, MI, stroke)
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Clop+ASA (%) |
Plac+ASA (%) |
RRR (%) |
P |
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Primary endpoint |
9.3 |
11.4 |
19.0 |
< 0.001 |
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MI |
5.2 |
6.7 |
22.0 |
NS |
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CV death |
5.1 |
5.5 |
7.0 |
NS |
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Stroke |
1.2 |
1.4 |
15.0 |
NS |
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- Overall bleeding events increased by 69%
Reference:
Yusuf et al. N Engl J Med 2001; 345: 494-502.
This slide indicates results from a study that evaluated the efficacy and safety of the
antiplatelet agent clopidogrel when given with aspirin in patients with acute coronary syndromes
without ST-segment elevation.
The antiplatelet agent clopidogrel has beneficial effects in patients with acute coronary syndromes without
ST-segment elevation. For the primary endpoint, the combination of clopidogrel and aspirin versus aspirin
alone showed a 19% relative risk reduction, which was statistically significant.
The risk of major bleeding is significantly increased among patients treated with clopidogrel.
There was no statistically significant difference in the stroke risk reduction with the combination of clopidogrel
plus aspirin vs. aspirin alone.
It was shown that combining clopidogrel with aspirin may be superior to aspirin alone only in patients
with unstable angina. However, the role of long-term combined therapy with aspirin and clopidogrel in
a broader group of patients at high risk for cardiovascular events is unknown.
12,562 patients were randomly assigned to receive clopidogrel (300 mg immediately followed by 75 mg once daily)
(6,259 patients) or placebo (6,303 patients) in addition to aspirin for 3 to 12 months. The primary endpoint
was cardiovascular death, myocardial infarction and stroke, and refractory cardiac ischemia.
CURE: Net Event Rate.Combined Endpoints vs. Major Bleed
References:
Albers GW, Amarenco P. Stroke 2001; 32: 2948-2949.
Yusuf et al. N Engl J Med 2001; 345: 494-502.
This slide indicates the net event rate of the aspirin versus clopidogrel therapy by combining the percentages of
cardiovascular deaths, MI, and stroke with the percentage of major bleeding that was observed. In the
Aspirin group the percentage of primary endpoints was higher than in the Clopidogrel group. However,
the rate of major bleeding was lower in the Aspirin group than among patients treated with clopidogrel.
Consequently, the net event rate in patients with aspirin was only 14.1 % as compared to 13.0% in the
Clopidogrel group. Minor bleeding was twice as common in the Aspirin+Clopidogrel group, while fatal bleeding
complications were equally common in both treatment groups. |
