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Meta-Analysis
. 2011 Nov 9;2011(11):CD001272.
doi: 10.1002/14651858.CD001272.pub2.

Antiplatelet agents for intermittent claudication

Peng F Wong  1 , Lee Yee Chong, Dimitris P Mikhailidis, Peter Robless, Gerard Stansby
Affiliations
Meta-Analysis

Antiplatelet agents for intermittent claudication

Peng F Wong et al. Cochrane Database Syst Rev. .

Abstract

Background: Peripheral arterial disease (PAD) is common and is a marker of systemic atherosclerosis. Patients with symptoms of intermittent claudication (IC) are at increased risk of cardiovascular events (myocardial infarction (MI) and stroke) and of both cardiovascular and all cause mortality.

Objectives: To determine the effectiveness of antiplatelet agents in reducing mortality (all cause and cardiovascular) and cardiovascular events in patients with intermittent claudication.

Search methods: The Cochrane Peripheral Vascular Diseases group searched their Specialised Register (last searched April 2011) and CENTRAL (2011, Issue 2) for publications on antiplatelet agents and IC. In addition reference lists of relevant articles were also searched.

Selection criteria: Double-blind randomised controlled trials comparing oral antiplatelet agents versus placebo, or versus other antiplatelet agents in patients with stable intermittent claudication were included. Patients with asymptomatic PAD (stage I Fontaine), stage III and IV Fontaine PAD, and those undergoing or awaiting endovascular or surgical intervention were excluded.

Data collection and analysis: Data on methodological quality, participants, interventions and outcomes including all cause mortality, cardiovascular mortality, cardiovascular events, adverse events, pain free walking distance, need for revascularisation, limb amputation and ankle brachial pressure indices were collected. For each outcome, the pooled risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) was calculated.

Main results: A total of 12 studies with a combined total of 12,168 patients were included in this review. Antiplatelet agents reduced all cause (RR 0.76, 95% CI 0.60 to 0.98) and cardiovascular mortality (RR 0.54, 95% CI 0.32 to 0.93) in patients with IC compared with placebo. A reduction in total cardiovascular events was not statistically significant (RR 0.80, 95% CI 0.63 to 1.01). Data from two trials (which tested clopidogrel and picotamide respectively against aspirin) showed a significantly lower risk of all cause mortality (RR 0.73, 95% CI 0.58 to 0.93) and cardiovascular events (RR 0.81, 95% CI 0.67 to 0.98) with antiplatelets other than aspirin compared with aspirin. Antiplatelet therapy was associated with a higher risk of adverse events, including gastrointestinal symptoms (dyspepsia) (RR 2.11, 95% CI 1.23 to 3.61) and adverse events leading to cessation of therapy (RR 2.05, 95% CI 1.53 to 2.75) compared with placebo; data on major bleeding (RR 1.73, 95% CI 0.51, 5.83) and on adverse events in trials of aspirin versus alternative antiplatelet were limited. Risk of limb deterioration leading to revascularisation was significantly reduced by antiplatelet treatment compared with placebo (RR 0.65, 95% CI 0.43 to 0.97).

Authors' conclusions: Antiplatelet agents have a beneficial effect in reducing all cause mortality and fatal cardiovascular events in patients with IC. Treatment with antiplatelet agents in this patient group however is associated with an increase in adverse effects, including GI symptoms, and healthcare professionals and patients need to be aware of the potential harm as well as the benefit of therapy; more data are required on the effect of antiplatelets on major bleeding. Evidence on the effectiveness of aspirin versus either placebo or an alternative antiplatelet agent is lacking. Evidence for thienopyridine antiplatelet agents was particularly compelling and there is an urgent need for multicentre trials to compare the effects of aspirin against thienopyridines.

PubMed Disclaimer

Conflict of interest statement

DM: "I have attended meetings and advisory boards and given some lectures sponsored by Merck, Sharp and Dohme (MSD) and Genzyme. I am editor‐in‐chief of several journals. Hence some royalties are paid to me (Bentham publications, SAGE publications and Informa publications)."

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Antiplatelet agent versus placebo, Outcome 1 All cause mortality.
1.2
1.2. Analysis
Comparison 1 Antiplatelet agent versus placebo, Outcome 2 Cardiovascular mortality (fatal stroke or MI).
1.3
1.3. Analysis
Comparison 1 Antiplatelet agent versus placebo, Outcome 3 Cardiovascular event (fatal and non‐fatal MI or stroke).
1.4
1.4. Analysis
Comparison 1 Antiplatelet agent versus placebo, Outcome 4 Myocardial infarction (fatal and non‐fatal).
1.5
1.5. Analysis
Comparison 1 Antiplatelet agent versus placebo, Outcome 5 Myocardial infarction (fatal).
1.6
1.6. Analysis
Comparison 1 Antiplatelet agent versus placebo, Outcome 6 Myocardial infarction (non‐fatal).
1.7
1.7. Analysis
Comparison 1 Antiplatelet agent versus placebo, Outcome 7 Stroke (fatal and non‐fatal).
1.8
1.8. Analysis
Comparison 1 Antiplatelet agent versus placebo, Outcome 8 Stroke (fatal).
1.9
1.9. Analysis
Comparison 1 Antiplatelet agent versus placebo, Outcome 9 Stroke (non‐fatal).
1.10
1.10. Analysis
Comparison 1 Antiplatelet agent versus placebo, Outcome 10 Major bleeding.
1.11
1.11. Analysis
Comparison 1 Antiplatelet agent versus placebo, Outcome 11 GI symptoms (dyspepsia).
1.12
1.12. Analysis
Comparison 1 Antiplatelet agent versus placebo, Outcome 12 Early cessation of treatment.
1.13
1.13. Analysis
Comparison 1 Antiplatelet agent versus placebo, Outcome 13 Pain Free Walking Distance.
1.14
1.14. Analysis
Comparison 1 Antiplatelet agent versus placebo, Outcome 14 Revascularisation.
1.15
1.15. Analysis
Comparison 1 Antiplatelet agent versus placebo, Outcome 15 Limb amputations.
2.1
2.1. Analysis
Comparison 2 Antiplatelet agent(s) versus aspirin, Outcome 1 All cause mortality.
2.2
2.2. Analysis
Comparison 2 Antiplatelet agent(s) versus aspirin, Outcome 2 Cardiovascular mortality (fatal stroke or MI).
2.3
2.3. Analysis
Comparison 2 Antiplatelet agent(s) versus aspirin, Outcome 3 Cardiovascular event (fatal and non‐fatal MI or stroke).
2.4
2.4. Analysis
Comparison 2 Antiplatelet agent(s) versus aspirin, Outcome 4 Myocardial infarction (fatal and non‐fatal).
2.5
2.5. Analysis
Comparison 2 Antiplatelet agent(s) versus aspirin, Outcome 5 Myocardial infarction (fatal).
2.6
2.6. Analysis
Comparison 2 Antiplatelet agent(s) versus aspirin, Outcome 6 Myocardial infarction (non‐fatal).
2.7
2.7. Analysis
Comparison 2 Antiplatelet agent(s) versus aspirin, Outcome 7 Stroke (fatal and non‐fatal).
2.8
2.8. Analysis
Comparison 2 Antiplatelet agent(s) versus aspirin, Outcome 8 Stroke (fatal).
2.9
2.9. Analysis
Comparison 2 Antiplatelet agent(s) versus aspirin, Outcome 9 Stroke (non‐fatal).
2.10
2.10. Analysis
Comparison 2 Antiplatelet agent(s) versus aspirin, Outcome 10 Major bleeding.
2.11
2.11. Analysis
Comparison 2 Antiplatelet agent(s) versus aspirin, Outcome 11 GI symptoms (dyspepsia).
2.12
2.12. Analysis
Comparison 2 Antiplatelet agent(s) versus aspirin, Outcome 12 Early cessation of treatment.
2.13
2.13. Analysis
Comparison 2 Antiplatelet agent(s) versus aspirin, Outcome 13 Amputation.
See this image and copyright information in PMC

Comment in

References

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