Antiplatelet agents for preventing thrombosis after peripheral arterial bypass surgery

Rachel B Forster; Anne Lethaby; Heather Maxwell; Stefan Acosta; Martin H Prins

doi:10.1002/14651858.CD000535.pub3

Cochrane Database of Systematic Reviews

Agentes antiplaquetarios para prevenir la trombosis después de la cirugía de derivación arterial periférica

Información

DOI:

https://doi.org/10.1002/14651858.CD000535.pub3 Copiar DOI

Base de datos:

Cochrane Database of Systematic Reviews

Versión publicada:

19 febrero 2015see what's new

Tipo:

Intervention

Etapa:

Review

Grupo Editorial Cochrane:

Grupo Cochrane de Vascular

Copyright:

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Contraer

Autores

Rachel B Forster

Correspondencia a: Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK

[email protected]
Anne Lethaby

Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand
Heather Maxwell

Edinburgh, UK
Stefan Acosta

Department of Vascular Diseases, Malmö University Hospital, Malmö, Sweden
Martin H Prins

Department of Epidemiology, CAPHRI Research School, Maastricht University, Maastricht, Netherlands

Contributions of authors

RB: performed study selection, data extraction and quality assessment and wrote the review update
AL: performed study selection, data extraction and quality assessment
HM: provided support in updating the manuscript
SA: provided support in updating the manuscript
MP: provided support in updating the manuscript

Sources of support

Internal sources

No sources of support provided

External sources

Chief Scientist Office, Scottish Government Health Directorates, The Scottish Government, UK

The PVD Group editorial base is supported by the Chief Scientist Office.

Declarations of interest

RB: none known
AL: none known
HM: none known
SA: none known
MP: Prof Prins' institution has received a grant from ZON‐MW (not‐for‐profit organisation) for demonstrating cost‐effectiveness on the topic of this review. Prof Prins' institution has received funding for his board membership of clinical studies and consultancy from Bayer, Boeringer Ingelheim, Daiichi Sankyo, Pfizer and ISIS Pharmaceuticals. These were not related to this review.

Acknowledgements

A special thank you to Karen Welch for assistance with German translation for several of the included studies.

We would like to thank the authors of the previous versions of the this review: Julie Brown, Andrew Wawryzniak, Janine Dörffler Melly, Marianne Koopmann, Harry Büller and Donald Adam.

The authors would like to thank the Peripheral Vascular Diseases Review group for their support and guidance.

Version history

Published

Title

Stage

Authors

Version

2015 Feb 19

Antiplatelet agents for preventing thrombosis after peripheral arterial bypass surgery

Review

Rachel B Forster, Anne Lethaby, Heather Maxwell, Stefan Acosta, Martin H Prins

https://doi.org/10.1002/14651858.CD000535.pub3

2008 Oct 08

Antiplatelet agents for preventing thrombosis after peripheral arterial bypass surgery

Review

Julie Brown, Anne Lethaby, Heather Maxwell, Andrew J Wawrzyniak, Martin H Prins

https://doi.org/10.1002/14651858.CD000535.pub2

2003 Jul 21

Antiplatelet agents for preventing thrombosis after peripheral arterial bypass surgery

Review

Janine Dörffler‐Melly, Harry R Büller, Marianne M Koopman, Martin H Prins

https://doi.org/10.1002/14651858.CD000535

Differences between protocol and review

We amended the outcome 'Limb salvage rate: survival rates with limb intact' to included 'or limb amputation', as most studies reported amputations, but not necessarily limb salvage rate.

We amended the outcome 'Side effects of treatment' to include 'and complications', as in several studies these two outcome types were grouped together.

Notes

Keywords

MeSH

Medical Subject Headings (MeSH) Keywords

Medical Subject Headings Check Words

Humans;

PICO

Population

Intervention

Comparison

Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Figure 1

Study flow diagram.

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Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Analysis 1.1

Comparison 1: ASA or ASA/DIP vs placebo or nothing, all grafts, Outcome 1: Primary graft patency at 12 months

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Analysis 1.2

Comparison 1: ASA or ASA/DIP vs placebo or nothing, all grafts, Outcome 2: Side effects and complications

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Analysis 1.3

Comparison 1: ASA or ASA/DIP vs placebo or nothing, all grafts, Outcome 3: Limb amputation

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Analysis 1.4

Comparison 1: ASA or ASA/DIP vs placebo or nothing, all grafts, Outcome 4: Cardiovascular events

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Analysis 1.5

Comparison 1: ASA or ASA/DIP vs placebo or nothing, all grafts, Outcome 5: Mortality

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Analysis 2.1

Comparison 2: ASA or ASA/DIP vs placebo or nothing, subgroups, Outcome 1: Primary graft patency, venous grafts, 1 month

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Analysis 2.2

Comparison 2: ASA or ASA/DIP vs placebo or nothing, subgroups, Outcome 2: Primary graft patency, venous grafts, 3 months

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Analysis 2.3

Comparison 2: ASA or ASA/DIP vs placebo or nothing, subgroups, Outcome 3: Primary graft patency, venous grafts, 6 months

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Analysis 2.4

Comparison 2: ASA or ASA/DIP vs placebo or nothing, subgroups, Outcome 4: Primary graft patency, venous grafts, 12 months

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Analysis 2.5

Comparison 2: ASA or ASA/DIP vs placebo or nothing, subgroups, Outcome 5: Primary graft patency, venous grafts, 24 months

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Analysis 2.6

Comparison 2: ASA or ASA/DIP vs placebo or nothing, subgroups, Outcome 6: Primary graft patency, prosthetic grafts, 1 month

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Analysis 2.7

Comparison 2: ASA or ASA/DIP vs placebo or nothing, subgroups, Outcome 7: Primary graft patency, prosthetic grafts, 3 months

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Analysis 2.8

Comparison 2: ASA or ASA/DIP vs placebo or nothing, subgroups, Outcome 8: Primary graft patency, prosthetic grafts, 6 months

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Analysis 2.9

Comparison 2: ASA or ASA/DIP vs placebo or nothing, subgroups, Outcome 9: Primary graft patency, prosthetic grafts, 9 months

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Analysis 2.10

Comparison 2: ASA or ASA/DIP vs placebo or nothing, subgroups, Outcome 10: Primary graft patency, prosthetic grafts, 12 months

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Analysis 3.1

Comparison 3: ASA or ASA/DIP versus pentoxifylline (PTX), all grafts, Outcome 1: Primary graft patency, 1 month

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Analysis 3.2

Comparison 3: ASA or ASA/DIP versus pentoxifylline (PTX), all grafts, Outcome 2: Primary graft patency, 3 months

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Analysis 3.3

Comparison 3: ASA or ASA/DIP versus pentoxifylline (PTX), all grafts, Outcome 3: Primary graft patency, 6 months

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Analysis 3.4

Comparison 3: ASA or ASA/DIP versus pentoxifylline (PTX), all grafts, Outcome 4: Primary graft patency, 12 months

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Analysis 3.5

Comparison 3: ASA or ASA/DIP versus pentoxifylline (PTX), all grafts, Outcome 5: Side effects

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Analysis 3.6

Comparison 3: ASA or ASA/DIP versus pentoxifylline (PTX), all grafts, Outcome 6: Limb amputation

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Analysis 3.7

Comparison 3: ASA or ASA/DIP versus pentoxifylline (PTX), all grafts, Outcome 7: Mortality

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Analysis 4.1

Comparison 4: ASA/DIP versus indobufen, prosthetic grafts, Outcome 1: Primary graft patency, 3 months

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Analysis 4.2

Comparison 4: ASA/DIP versus indobufen, prosthetic grafts, Outcome 2: Primary graft patency, 6 months

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Analysis 4.3

Comparison 4: ASA/DIP versus indobufen, prosthetic grafts, Outcome 3: Primary graft patency, 9 months

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Analysis 4.4

Comparison 4: ASA/DIP versus indobufen, prosthetic grafts, Outcome 4: Primary graft patency, 12 months

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Analysis 5.1

Comparison 5: ASA or ASA/DIP versus vitamin K antagonists, all grafts, Outcome 1: Primary graft patency, 3 months

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Analysis 5.2

Comparison 5: ASA or ASA/DIP versus vitamin K antagonists, all grafts, Outcome 2: Primary graft patency, 6 months

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Analysis 5.3

Comparison 5: ASA or ASA/DIP versus vitamin K antagonists, all grafts, Outcome 3: Primary graft patency, 12 months

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Analysis 5.4

Comparison 5: ASA or ASA/DIP versus vitamin K antagonists, all grafts, Outcome 4: Primary graft patency, 24 months

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Analysis 5.5

Comparison 5: ASA or ASA/DIP versus vitamin K antagonists, all grafts, Outcome 5: Limb amputation

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Analysis 5.6

Comparison 5: ASA or ASA/DIP versus vitamin K antagonists, all grafts, Outcome 6: Cardiovascular events

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Analysis 5.7

Comparison 5: ASA or ASA/DIP versus vitamin K antagonists, all grafts, Outcome 7: Mortality

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Analysis 6.1

Comparison 6: ASA/DIP versus LMWH, all grafts, Outcome 1: Primary graft patency, 6 months

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Analysis 6.2

Comparison 6: ASA/DIP versus LMWH, all grafts, Outcome 2: Primary graft patency, 12 months

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Analysis 6.3

Comparison 6: ASA/DIP versus LMWH, all grafts, Outcome 3: Mortality

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Analysis 7.1

Comparison 7: Ticlopidine versus placebo, venous grafts, Outcome 1: Primary graft patency, 1 month

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Analysis 7.2

Comparison 7: Ticlopidine versus placebo, venous grafts, Outcome 2: Primary graft patency, 6 months

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Analysis 7.3

Comparison 7: Ticlopidine versus placebo, venous grafts, Outcome 3: Primary graft patency, 12 months

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Analysis 7.4

Comparison 7: Ticlopidine versus placebo, venous grafts, Outcome 4: Primary graft patency, 24 months

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Analysis 8.1

Comparison 8: ASA versus prostaglandin (PGE1), venous grafts, Outcome 1: Early occlusion

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Analysis 9.1

Comparison 9: ASA versus naftidrofuryl, Outcome 1: Primary graft patency at 12 months

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Analysis 9.2

Comparison 9: ASA versus naftidrofuryl, Outcome 2: Side effects

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Analysis 9.3

Comparison 9: ASA versus naftidrofuryl, Outcome 3: Mortality

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Analysis 10.1

Comparison 10: Clopidogrel and ASA versus ASA alone, all grafts, Outcome 1: Primary graft patency at 24 months

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Analysis 10.2

Comparison 10: Clopidogrel and ASA versus ASA alone, all grafts, Outcome 2: Side effects

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Analysis 10.3

Comparison 10: Clopidogrel and ASA versus ASA alone, all grafts, Outcome 3: Limb amputation

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Analysis 10.4

Comparison 10: Clopidogrel and ASA versus ASA alone, all grafts, Outcome 4: Mortality

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Analysis 11.1

Comparison 11: Clopidogrel and ASA versus ASA alone, subgroups, Outcome 1: Primary graft patency, venous grafts, 24 months

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Analysis 11.2

Comparison 11: Clopidogrel and ASA versus ASA alone, subgroups, Outcome 2: Primary graft patency, prosthetic grafts, 24 months

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Analysis 11.3

Comparison 11: Clopidogrel and ASA versus ASA alone, subgroups, Outcome 3: Side effects

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Analysis 11.4

Comparison 11: Clopidogrel and ASA versus ASA alone, subgroups, Outcome 4: Limb amputation

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Analysis 11.5

Comparison 11: Clopidogrel and ASA versus ASA alone, subgroups, Outcome 5: Mortality

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Table 1. Patient characteristics

Study ID	% CLI	% below knee	% vein	% 1‐vessel run‐off	dose	preoperative start of treatment	treatment duration	randomisation	ABI pre‐op to postop
Becquemin 1997	> 70	nd	100	nd	TIC 250 mg vs placebo	between the 3rd and 14th post‐op day	24 months	post‐op	nd
BOA 2000	50	52	58.5	nd	ASA 80 mg vs coumarin INR 3.0 ‐ 4.5 reached in 50%	within 5 days until 1 month post‐op	21 months	before surgery	nd
CASPAR 2010	66	100	70	nd	ASA 75 ‐ 100 mg plus clopidogrel 75 mg vs ASA 75 ‐ 100 mg plus placebo	2 to 4 days post‐op	24 months	post‐op	nd
Clyne 1987	70	85	63	24	ASA 2 x 300 mg, DIP 2 x 200 mg	48 hours pre‐op	6 weeks	before surgery	0.38 to 0.78
D'Addato 1992	70	25	0	56	ASA 900 mg plus DIP 225 mg vs 400 mg IND	48 h	12 months	before surgery	nd
Donaldson 1985	0	32	0	37	ASA 3 x 330 mg plus DIP 75 mg	Evening prior to surgery	12 months	before surgery	0.62 to nd
Edmondson 1994	46	31	27	20	3 x 300 mg ASA plus 3 x 100 mg DIP versus 2500 IU LMWH	LMWH 2 hours pre‐op; ASA/DIP 1 week post‐op	3 months	post‐op	nd
Goldman 1984	80	47	0	nd	ASA 3 x 300 mg plus DIP 3 x 75 mg	2 days ASA/DIP	12 months	before surgery	nd
Green 1982	82	47	0	nd	ASA 3 x 325 mg, or ASA 3 x 325 mg plus DIP 3 x 75 mg	2 days ASA/DIP	12 months	before surgery	0.42 to 1.01
Gruss 1991	nd	nd	100	nd	3 x 0.5 g ASA plus 15,000 IU heparin versus PGE1, 0.2 ng per kg body weight/min plus 15,000 IU heparin	post‐op	10 days	nd	nd
Kohler 1984	76	52	69	nd	ASA 3 x 325 mg plus DIP 3 x 75 mg	first post‐op day	24 months	before surgery	nd
Lucas 1984	55	nd	27	nd	ASA 1050 mg, DIP 150 mg or 1200 mg PTX	pre‐op	6 months	before surgery	0.4
McCollum 1991	60	59	100	nd; vein < 4 mm:38	ASA 2 x 300 mg plus DIP 2 x 150 mg	2 days ASA/DIP	continuing indefinitely	before surgery	0.47 to nd
Noppeney 1988	nd	nd	nd	nd	ASA 1500 mg vs naftidrofuryl 600 mg daily orally	day 1 post‐op	12 months	before surgery	nd
Raithel 1987	95	nd	0	56	ASA 1500 mg vs PTX 1200 mg	48 h	12 months	before surgery	nd
Schneider 1979	nd	nd	100	nd	ASA 1000 mg, or ASA 1000 mg plus DIP 225 mg vs coumarin	post‐op	24 months	post‐op	nd
ASA: Aspirin CLI: critical limb ischaemia DIP: dipyridamole h: hour IU: international unit LMWH: low molecular weight heparin mg: milligram nd: no data ng: nanogram PGE1: prostaglandin E1 PTX: pentoxifylline TIC: ticlopidine vs: versus

Table 1. Patient characteristics

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Comparison 1. ASA or ASA/DIP vs placebo or nothing, all grafts

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Primary graft patency at 12 months Show forest plot	6	952	Odds Ratio (M‐H, Random, 95% CI)	0.42 [0.22, 0.83]

1.2 Side effects and complications Show forest plot	6		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.2.1 Side effects‐ general	5	913	Odds Ratio (M‐H, Fixed, 95% CI)	1.55 [1.00, 2.41]
1.2.2 Gastrointestinal side effects	6	952	Odds Ratio (M‐H, Fixed, 95% CI)	1.44 [0.92, 2.24]
1.2.3 Major bleeding	2	598	Odds Ratio (M‐H, Fixed, 95% CI)	1.88 [0.85, 4.16]
1.2.4 Minor bleeding	1	148	Odds Ratio (M‐H, Fixed, 95% CI)	0.73 [0.31, 1.70]
1.2.5 Wound or graft infection	1	549	Odds Ratio (M‐H, Fixed, 95% CI)	1.07 [0.67, 1.71]
1.3 Limb amputation Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

1.4 Cardiovascular events Show forest plot	4	811	Odds Ratio (M‐H, Random, 95% CI)	1.27 [0.43, 3.80]

1.5 Mortality Show forest plot	4	799	Odds Ratio (M‐H, Fixed, 95% CI)	0.84 [0.56, 1.26]

Comparison 1. ASA or ASA/DIP vs placebo or nothing, all grafts

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Comparison 2. ASA or ASA/DIP vs placebo or nothing, subgroups

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Primary graft patency, venous grafts, 1 month Show forest plot	2	642	Odds Ratio (M‐H, Fixed, 95% CI)	0.76 [0.26, 2.25]

2.2 Primary graft patency, venous grafts, 3 months Show forest plot	2	642	Odds Ratio (M‐H, Fixed, 95% CI)	0.85 [0.54, 1.35]

2.3 Primary graft patency, venous grafts, 6 months Show forest plot	2	642	Odds Ratio (M‐H, Fixed, 95% CI)	0.88 [0.59, 1.31]

2.4 Primary graft patency, venous grafts, 12 months Show forest plot	2	642	Odds Ratio (M‐H, Fixed, 95% CI)	0.69 [0.48, 0.99]

2.5 Primary graft patency, venous grafts, 24 months Show forest plot	2	620	Odds Ratio (M‐H, Random, 95% CI)	1.03 [0.32, 3.28]

2.6 Primary graft patency, prosthetic grafts, 1 month Show forest plot	3	157	Odds Ratio (M‐H, Fixed, 95% CI)	0.14 [0.04, 0.51]

2.7 Primary graft patency, prosthetic grafts, 3 months Show forest plot	4	222	Odds Ratio (M‐H, Fixed, 95% CI)	0.31 [0.14, 0.66]

2.8 Primary graft patency, prosthetic grafts, 6 months Show forest plot	4	222	Odds Ratio (M‐H, Fixed, 95% CI)	0.21 [0.11, 0.41]

2.9 Primary graft patency, prosthetic grafts, 9 months Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2.10 Primary graft patency, prosthetic grafts, 12 months Show forest plot	4	222	Odds Ratio (M‐H, Fixed, 95% CI)	0.19 [0.10, 0.36]

Comparison 2. ASA or ASA/DIP vs placebo or nothing, subgroups

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Comparison 3. ASA or ASA/DIP versus pentoxifylline (PTX), all grafts

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3.1 Primary graft patency, 1 month Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3.2 Primary graft patency, 3 months Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3.3 Primary graft patency, 6 months Show forest plot	2	151	Odds Ratio (M‐H, Fixed, 95% CI)	1.32 [0.56, 3.11]

3.4 Primary graft patency, 12 months Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3.5 Side effects Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3.5.1 Gastric intolerance	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
3.5.2 Gastric haemorrhage	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
3.5.3 Vertigo	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
3.6 Limb amputation Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3.7 Mortality Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 3. ASA or ASA/DIP versus pentoxifylline (PTX), all grafts

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Comparison 4. ASA/DIP versus indobufen, prosthetic grafts

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
4.1 Primary graft patency, 3 months Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4.2 Primary graft patency, 6 months Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4.3 Primary graft patency, 9 months Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4.4 Primary graft patency, 12 months Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 4. ASA/DIP versus indobufen, prosthetic grafts

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Comparison 5. ASA or ASA/DIP versus vitamin K antagonists, all grafts

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
5.1 Primary graft patency, 3 months Show forest plot	2	2781	Odds Ratio (M‐H, Fixed, 95% CI)	0.88 [0.68, 1.14]

5.2 Primary graft patency, 6 months Show forest plot	2	2781	Odds Ratio (M‐H, Random, 95% CI)	0.72 [0.27, 1.96]

5.3 Primary graft patency, 12 months Show forest plot	2	2781	Odds Ratio (M‐H, Random, 95% CI)	0.68 [0.27, 1.69]

5.4 Primary graft patency, 24 months Show forest plot	2	2781	Odds Ratio (M‐H, Random, 95% CI)	0.64 [0.25, 1.63]

5.5 Limb amputation Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

5.6 Cardiovascular events Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

5.6.1 Myocardial infarction	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
5.6.2 Stroke	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
5.7 Mortality Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 5. ASA or ASA/DIP versus vitamin K antagonists, all grafts

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Comparison 6. ASA/DIP versus LMWH, all grafts

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
6.1 Primary graft patency, 6 months Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

6.2 Primary graft patency, 12 months Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

6.3 Mortality Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 6. ASA/DIP versus LMWH, all grafts

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Comparison 7. Ticlopidine versus placebo, venous grafts

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
7.1 Primary graft patency, 1 month Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

7.2 Primary graft patency, 6 months Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

7.3 Primary graft patency, 12 months Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

7.4 Primary graft patency, 24 months Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 7. Ticlopidine versus placebo, venous grafts

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Comparison 8. ASA versus prostaglandin (PGE1), venous grafts

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
8.1 Early occlusion Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 8. ASA versus prostaglandin (PGE1), venous grafts

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Comparison 9. ASA versus naftidrofuryl

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
9.1 Primary graft patency at 12 months Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

9.2 Side effects Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

9.2.1 Side effects‐ general	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
9.2.2 Gastrointestinal side effects	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
9.2.3 Vertigo	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
9.2.4 Stomach bleeding	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
9.3 Mortality Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 9. ASA versus naftidrofuryl

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Comparison 10. Clopidogrel and ASA versus ASA alone, all grafts

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
10.1 Primary graft patency at 24 months Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

10.2 Side effects Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

10.2.1 Bleeding‐ total	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
10.2.2 Bleeding‐ mild	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
10.2.3 Bleeding‐ moderate	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
10.2.4 Bleeding‐ severe	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
10.2.5 Bleeding‐ fatal	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
10.3 Limb amputation Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

10.4 Mortality Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 10. Clopidogrel and ASA versus ASA alone, all grafts

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Comparison 11. Clopidogrel and ASA versus ASA alone, subgroups

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
11.1 Primary graft patency, venous grafts, 24 months Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

11.2 Primary graft patency, prosthetic grafts, 24 months Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

11.3 Side effects Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

11.3.1 Bleeding‐ mild, venous grafts	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
11.3.2 Bleeding‐ mild, prosthetic grafts	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
11.3.3 Bleeding‐ moderate, venous grafts	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
11.3.4 Bleeding‐ moderate, prosthetic grafts	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
11.3.5 Bleeding‐ severe, venous grafts	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
11.3.6 Bleeding‐ severe, prosthetic grafts	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
11.4 Limb amputation Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

11.4.1 Amputation, venous grafts	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
11.4.2 Amputation, prosthetic grafts	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
11.5 Mortality Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

11.5.1 Mortality, venous grafts	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
11.5.2 Mortality, prosthetic grafts	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 11. Clopidogrel and ASA versus ASA alone, subgroups

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Agentes antiplaquetarios para prevenir la trombosis después de la cirugía de derivación arterial periférica

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