Fibrinolytic agents for acute arterial occlusion (Protocol)

Berridge DC, Kessel DO, Robertson I

This is a reprint of a Cochrane protocol, prepared and maintained by The Cochrane Collaboration and published in The Cochrane
Library 1998, Issue 2
http://www.thecochranelibrary.com

Fibrinolytic agents for acute arterial occlusion (Protocol)

Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Fibrinolytic agents for acute arterial occlusion (Protocol) i

Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
[Intervention Protocol]

Fibrinolytic agents for acute arterial occlusion

David C Berridge2 , David O Kessel3 , Iain Robertson1

1
Department of Radiology, Gartnavel General Hospital, GLASGOW, UK. 2 Department of Vascular and Endovascular Surgery, St
James’s University Hospital, LEEDS, UK. 3 Department of Clinical Radiology, Leeds Teaching Hospitals Trust, Leeds, UK

Contact address: Iain Robertson, Department of Radiology, Gartnavel General Hospital, 1053 Great Western Road, GLASGOW, G12
0XN, UK. Iain.Robertson@NorthGlasgow.Scot.NHS.UK.

Editorial group: Cochrane Peripheral Vascular Diseases Group.

Publication status and date: Edited (no change to conclusions), published in Issue 4, 2008.

Citation: Berridge DC, Kessel DO, Robertson I. Fibrinolytic agents for acute arterial occlusion. Cochrane Database of Systematic
Reviews 1998, Issue 2. Art. No.: CD001099. DOI: 10.1002/14651858.CD001099.

Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT

This is the protocol for a review and there is no abstract. The objectives are as follows:

The objective of this review is to determine which is the most effective fibrinolytic agent in peripheral arterial thrombolysis. Outcome
measures will include limb salvage, amputation, death, vessel patency, time to lysis, and complications, specifically the risk of major
haemorrhage and stroke. The logistics of the various techniques will also be discussed. The specific hypotheses to be tested are:

1) There is no overall additional benefit from any of the different fibrinolytic agents available to the majority of patients suitable for
peripheral arterial thrombolysis.

2) Complication rates may be higher with certain fibrinolytic agents.

BACKGROUND staphylokinase are now being evaluated. Potential advantages in-

clude improved safety, greater efficacy, and more rapid response.
Peripheral arterial thrombolysis has become established as a useful
The newer thrombolytic agents also tend to be more expensive
adjunct to the management of peripheral arterial ischaemia. It is
than the more traditional agents. Concern over reuse of the agents
particularly useful for those cases of more recent onset, of less than
due to the production of antibodies and the subsequent risk of
two weeks duration (STILE 1994). Much is known about indica-
tions, risks and benefits using this technique, although data from reactions including anaphylaxis are also of particular importance.
randomised controlled studies are not extensive. There are rela-
tively few trials looking specifically at which is the optimal agent.
There are a number of fibrinolytic agents which have been used for OBJECTIVES
peripheral arterial thrombolysis. Streptokinase was the first to be
described, and is still the first-line drug used for coronary throm- The objective of this review is to determine which is the most ef-
bolysis. For peripheral arterial thrombolysis however, urokinase fective fibrinolytic agent in peripheral arterial thrombolysis. Out-
(preferred in the United States), recombinant tissue plasminogen come measures will include limb salvage, amputation, death, ves-
activator (rt-PA) (preferred in the UK), are the first-line drugs sel patency, time to lysis, and complications, specifically the risk of
and more recently drugs such as pro-urokinase and recombinant major haemorrhage and stroke. The logistics of the various tech-
Fibrinolytic agents for acute arterial occlusion (Protocol) 1
Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
niques will also be discussed. The specific hypotheses to be tested Search methods for identification of studies
are:
The Cochrane Peripheral Vascular Diseases Group will search their
1) There is no overall additional benefit from any of the different Specialised Register and the Cochrane Central Register of Con-
fibrinolytic agents available to the majority of patients suitable for trolled Trials (CENTRAL) in The Cochrane Library for all reports
peripheral arterial thrombolysis. of randomised clinical trials or controlled clinical trials of surgery
versus thrombolysis for acute limb ischaemia.The Specialised Reg-
2) Complication rates may be higher with certain fibrinolytic ister is constructed from electronic searches of MEDLINE (1950
agents. to date), EMBASE (1980 to date), CINAHL (1982 to date) and
AMED (1985 to date), and through handsearching relevant jour-
nals. The full list of journals that have been handsearched, as well
METHODS as the search strategies used are described in the ’Search strategies
for the identification of studies’ section within the editorial infor-
mation about the Cochrane PVD Group in The Cochrane Library,
http://www.mrw.interscience.wiley.com/cochrane/clabout/
Criteria for considering studies for this review articles/PVD/frame.html
Additional articles will be identified by reviewing reference lists
of papers resulting from this search. Proceedings from all British
Vascular Surgical Society, European Vascular Surgical Society and
Types of studies
North American Society of Vascular Surgery meetings, SCVIR and
This review will include trials in which participants have been CIRSE (Radiological Societies) will be scanned for relevant trials.
randomly allocated to different fibrinolytic agents for the purpose All major pharmaceutical firms will be asked about unpublished
of arterial thrombolysis. trials that fit the criteria described above. Authors of published
trials will be asked if they are aware of any relevant unpublished
trials.
Types of participants
Participants are those requiring peripheral arterial thrombolysis to
attempt to achieve patency following a thrombo-embolic occlu-
Data collection and analysis
sion of either a native peripheral artery or a thrombosed lower
limb graft. Dialysis grafts and fistulae will be excluded. Patients The selection of trials for inclusion in this review will be carried
will be included irrespective of diabetic status, use of aspirin or out independently by each of the two reviewers. One reviewer
anticoagulation post-thrombolysis, or use of concurrent heparin. (DCB) will identify all possible trials and send these to the second
reviewer (DK). Discrepancies will be resolved by discussion. The
criteria for selection of trials will be as specified in the above section
Types of interventions ’Criteria for Considering Trials for Review’.
The methodological quality of each trial will be assessed inde-
All types of interventions will be considered. The focus of the re-
pendently using the checklist provided by the Peripheral Vascular
view will be the randomised comparison of different agents, in-
Review Group with emphasis on concealment of randomisation.
cluding streptokinase, recombinant tissue plasminogen activator,
Each reviewer will give an allocation score of A (clearly concealed),
urokinase and recombinant staphylokinase irrespective of dose or
B (unclear if concealed) or C (clearly not concealed), and a sum-
duration. It is the choice of agent, not the subsequent intervention
mary score of A (low risk of bias) or C (high risk of bias). Trials
that will allow inclusion.
scoring B will be discussed and attempts made to obtain further
information from the authors. In the absence of consensus over
the inclusion of a particular trial, the opinion of a third reviewer
Types of outcome measures will be sought.
Outcome measures are as follows: Data collection on each trial will include information on partic-
1) Vessel patency ipants ( age, sex distribution, severity of disease as measured by
2) Time to lysis ABPIs and the European Consensus definition of critical ischaemia
3) Limb salvage (Dormandy 1991), Fontaine classification (Fontaine 1954), and
4) Amputation Ad Hoc Committee Recommendations (Rutherford 1986) where
5) Death possible, limb salvage vessel/graft patency, amputation, death and
6) Complications including major haemorrhage, strokes, distal complications.
embolisation. The data will be synthesised by comparing group results. Individ-

Fibrinolytic agents for acute arterial occlusion (Protocol) 2

Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
ual patient data from different trials will not be amalgamated. Sen-
sitivity analysis will be carried out if sufficient trials are identified.

REFERENCES
Additional references Rutherford 1986
Rutherford RB, Flanigan DP, Gupta SK, Johnston KW,
Dormandy 1991 Karmody A, Whittemore AD, et al.Suggested standards for
Dormandy J. European Working Group on Critical Chronic reports dealing with lower extremity ischaemia. J Vasc Surg
Ischaemia. Second European Consensus Document on 1986;4:80–94.
Chronic Critical Leg Ischaemia. Circulation 1991;84
(suppl4):1–26. STILE 1994
Fontaine 1954 The STILE Investigators. Results of a prospective
Fontaine VR, Kim M, Kieny R. Surgical treatment for randomised trial evaluating surgery versus thrombolysis for
peripheral vascular disease [Die chirurgische Behandlung ischaemia of the lower extremity. The STILE trial. Annals
der peripheren Durchblutungsstorungen]. Helvetica of Surgery 1994;220(3):251–266.
Chirurgica Acta 1954;5/6:499–533. ∗
Indicates the major publication for the study

WHAT’S NEW

Date Event Description

13 August 2008 Amended Converted to new review format.

HISTORY
Protocol first published: Issue 2, 1998

CONTRIBUTIONS OF AUTHORS
David Berridge: will identify all possible trials, consider them for inclusion; and assess trial quality.
David Kessel: will consider trials for inclusion and assess quality.
In cases where disagreement exists between the reviewers, the opinion of a third reviewer will be sought.

DECLARATIONS OF INTEREST
None

Fibrinolytic agents for acute arterial occlusion (Protocol) 3

Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
SOURCES OF SUPPORT

Internal sources
• St James’s University NHS Hospital, UK.

External sources
• Chief Scientist Office, Scottish Government Health Directorates, The Scottish Government, UK.

Fibrinolytic agents for acute arterial occlusion (Protocol) 4

Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.