| Author, date |
Patient group |
Outcomes |
Key results |
Weaknesses/comments |
| and country |
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|
| Study type |
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|
| (Level of |
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| evidence) |
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| Chan et al. 2005, |
320 patients with previous |
Peptic ulcer |
13 patients in clopidogrel |
No patients included with |
| N Eng J Med, |
GI bleeding on |
bleeding |
group (OR 8.6, CI 4.1–13.1) |
low-dose aspirin without |
| Hong Kong, [2] |
cardiovascular aspirin dose, |
|
vs. 1 patient in aspirin plus |
prophylaxis |
|
and endoscopically proven |
|
esomeprazole group |
|
| Double-blind |
ulcer healing, H. Pylori |
|
(OR 0.7, CI 0–2.0) |
Results possibly not applicable |
| PRCT (Level 1b) |
negative, no other |
|
(P=0.001, NNT 13) |
to all patients in view of |
|
antiplatelet treatment |
|
|
population characteristics |
|
Follow-up 12 months |
Lower GI |
7 patients in clopidogrel |
|
|
|
bleeding |
group (OR 4.6, CI 1.3–7.9) |
Study drugs were repacked |
|
Two groups: 159 patients |
|
vs. 7 patients in aspirin |
maybe influencing uptake and |
|
80 mg aspirin plus 20 mg |
|
plus esomeprazole group |
resorption |
|
esomeprazole twice daily |
|
(OR 4.6, CI 1.3–7.9) |
|
|
vs. 161 patients 75 mg |
|
(P=0.98) |
|
|
clopidogrel daily plus |
|
|
|
|
placebo |
Extra- |
3 patients in clopidogrel group |
|
|
|
intestinal |
|
|
|
|
bleeding |
No patient in aspirin plus |
|
|
|
|
esomeprazole group |
|
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|
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|
|
Mortality |
8 patients in clopidogrel group |
|
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4 patients in aspirin plus |
|
|
|
|
esomeprazole group |
|
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|
|
| Ibanez et al. 2006, |
9841 study participants |
Upper GI |
Antiplatelet drugs cause 14.5% of all upper GI bleedings |
| Aliment |
|
bleeding |
|
| Pharmacol |
Two groups: 2783 patients |
|
467 patients and 642 controls on aspirin (OR 4.0, CI 3.2–4.9) vs. |
| Ther, Spain and |
admitted for upper GI |
|
15 patients and 29 controls on aspirin and PPI |
| Italy, [3] |
bleeding of which 546 |
|
(OR 1.1, CI 0.5–2.6) |
|
patients on antiplatelet |
|
|
| Case-control |
therapy alone, 130 patients |
|
As well decrease PPI's non-aspirin anti-platelet drugs from |
| Study (Level 3b) |
on PPIs alone, 27 patients |
|
OR 2.1 (1.5–2.9) to OR 0.9 (0.4–2.3) |
|
on antiplatelet therapy and |
|
|
|
PPIs. |
|
12 patients and 17 controls on clopidogrel (OR 2.3, CI 0.9–6.0) |
|
7058 controls matched to |
|
|
|
centre, date of admission, |
|
12 patients and 17 controls on dipyridamole (OR 0.9, CI 0.4–2.0) |
|
gender, age. Of these 804 |
|
|
|
patients on antiplatelet |
|
10 patients and 10 controls on indobufen (OR 3.8, CI 1.2–12.2) |
|
therapy alone, 278 patients |
|
|
|
on PPIs alone, 49 patients |
|
52 patients and 55 controls on ticlopidine (OR 3.1, CI 1.8–5.1). |
|
on antiplatelet therapy and |
|
Dose related increased risk on ticlopidine |
|
PPIs |
|
|
|
|
|
28 patients and 66 controls on triflusal (OR 1.8, CI 0.9–3.5) |
|
|
|
|
| Ng et al. 2004, |
129 patients on low-dose |
Endoscopically |
No evidence of bleeding, |
Endpoint of eight weeks may |
| Aliment |
aspirin (80–160 mg daily) |
proven |
perforation or obstruction in |
not be sufficient |
| Pharmacol |
with active minor peptic |
ulcer healing |
either group |
|
| Ther, Hong |
ulcer disease |
within eight |
|
Small numbers, and |
| Kong, [4] |
|
weeks of |
4 patients with ongoing |
underpowered for treatment |
|
Two groups: All patients |
treatment |
minor peptic ulcer disease or |
effect (minimum of 400 |
| Single-blind |
received 20 mg omeprazole |
|
erosions in clopidogrel |
patients for each arm) |
| PRCT (Level |
daily. |
|
group vs. three patients in |
|
| 1b) |
69 patients received 75 mg |
|
the aspirin group |
Patients with high risk peptic |
|
clopidogrel daily and 60 |
|
|
ulcer disease were excluded |
|
patients continued their |
|
|
|
|
daily low-dose aspirin |
|
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|
|
|
| Lai et al. 2006, |
170 patients on low-dose |
Recurrent |
No patient in aspirin plus |
Results possibly not applicable |
| Clin Gastro Hepat, |
aspirin with previous ulcer |
peptic ulcer |
esomeprazole group had |
to all patients in view of |
| Hong Kong, [5] |
bleeding, negative for H. |
complications |
complications (CI 0) |
population characteristics |
|
pylori, proven ulcer |
within |
|
|
| Double-blind |
healing |
12 months |
9 patients in clopidogrel |
|
| PRCT (Level 1b) |
|
follow-up |
group (OR 13.6 CI 6.3–20.9) |
|
|
Two groups: 86 patients |
|
(P=0.0019) |
|
|
received 100 mg aspirin |
|
|
|
|
plus 20 mg esomeprazole |
|
|
|
|
|
|
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|
|
daily and 84 patients |
|
|
|
|
received 75 mg clopidogrel |
|
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|
|
daily |
|
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|
|
|
|
|
|
| Ng et al. 2003, |
70 patients previous |
Reoccurrence of |
9 patients (12%) with GI |
Small numbers, and |
| Aliment |
history of non-aspirin |
ulcer |
bleeding and 1 patient with |
underpowered for treatment |
| Pharmacol |
peptic ulcer disease or |
complications |
perforated peptic ulcer. No |
effect |
| Ther, Hong Kong, |
aspirin related GI |
|
patient was on maintenance |
|
| [6] |
complications (dyspepsia |
|
PPI therapy |
No control group |
|
or peptic ulcer) received |
|
|
|
| Retrospective |
75 mg clopidogrel daily |
|
Clopidogrel increased risk in |
No standardised use of acid |
| cohort study |
|
|
patients with previous GI |
suppression because of |
| (Level 2b) |
Follow-up 12 months |
|
bleeding vs. patients without |
retrospective study |
|
|
|
previous GI bleeding |
|
|
|
|
(22% vs. 0%, P=0.007, |
Results possibly not applicable |
|
|
|
OR 1.3, CI 1.1–1.5) |
to all patients in view of |
|
|
|
|
population characteristics |
|
|
|
|
|
| CAPRIE Study |
19,185 patients with |
Occurrence of |
2800 outcome events. 1171 |
|
| Organisation |
previous ischaemic stroke, |
ischaemic |
patients on clopidogrel |
|
| 1996, Lancet, |
MI or atherosclerotic |
stroke, MI, |
and 1236 patients on aspirin |
|
| USA and |
peripheral arterial disease |
vascular death |
with one event of whom 158 |
|
| Europe, [7] |
|
|
patients on clopidogrel and |
|
|
Two groups: 9586 patients |
|
182 patients on aspirin |
|
| Multicentre |
received 325 mg aspirin |
|
had 1 event. RR reduction |
|
| Double-blind |
daily. |
|
for clopidogrel 8.7% |
|
| PRCT (Level 1b) |
9599 patients received |
|
(CI 0.3–16.5, P=0.043) |
|
|
75 mg clopidogrel daily |
|
|
|
|
|
|
Annual risk for clopidogrel |
|
|
|
|
5.32% vs. aspirin 5.83% |
|
|
|
|
|
|
|
|
Any bleeding |
890 patients (9.27%) on |
|
|
|
|
clopidogrel and 890 |
|
|
|
|
patients (9.28%) on aspirin |
|
|
|
|
(RR 1.00, CI 0.92–1.09) |
|
|
|
|
|
|
|
|
GI bleeding |
191 patients (1.99%) on |
|
|
|
|
clopidogrel vs. 255 patients |
|
|
|
|
(2.66%) on aspirin |
|
|
|
|
(RR 1.34, CI 1.11–1.61, |
|
|
|
|
P<0.05) |
|
