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Aspirin to target arterial events in chronic kidney disease (ATTACK): study protocol for a multicentre, prospective, randomised, open-label, blinded endpoint, parallel group trial of low-dose aspirin vs. standard care for the primary prevention of cardiovascular disease in people with chronic kidney disease

Aspirin to target arterial events in chronic kidney disease (ATTACK): study protocol for a multicentre, prospective, randomised, open-label, blinded endpoint, parallel group trial of low-dose aspirin vs. standard care for the primary prevention of cardiovascular disease in people with chronic kidney disease
Aspirin to target arterial events in chronic kidney disease (ATTACK): study protocol for a multicentre, prospective, randomised, open-label, blinded endpoint, parallel group trial of low-dose aspirin vs. standard care for the primary prevention of cardiovascular disease in people with chronic kidney disease
Background: Chronic Kidney Disease (CKD) is a very common long-term condition and powerful risk factor for Cardiovascular Disease (CVD).
Low dose aspirin is of proven benefit in the secondary prevention of myocardial infarction (MI) and stroke in people with pre-existing CVD. However, in people without CVD the rates of MI and stroke are much lower, and the benefits of aspirin in the primary prevention of CVD are largely balanced by an increased risk of bleeding.
People with CKD are at greatly increased risk of CVD and so the absolute benefits of aspirin are likely to be greater than in lower risk groups, even if the relative benefits are the same. Post-hoc evidence suggests the relative benefits may be greater in the CKD population but the risk of bleeding may also be higher. A definitive study of aspirin for primary prevention in this high risk group, recommended by the National Institute for Health and Care Excellence (NICE) in 2014, has never been conducted. The question has global significance given the rising burden of CKD worldwide and the low cost of aspirin.

Methods: ATTACK is a pragmatic multicentre, prospective, randomised, open-label, blinded endpoint adjudication superiority trial of aspirin 75 mg daily vs. standard care for the primary prevention of CVD in 25,210 people aged 18 years and over with CKD recruited from UK Primary Care.
Participants aged 18 years and over with CKD (GFR category G1-G4) will be identified in Primary Care and followed up using routinely collected data and annual questionnaires for an average of 5 years. The primary outcome is the time to first major vascular event (composite of non-fatal MI, non-fatal stroke and cardiovascular death [excluding confirmed intracranial haemorrhage and other fatal cardiovascular haemorrhage]). Deaths from other causes (including fatal bleeding) will be treated as competing events. The study will continue until 1,827 major vascular events have occurred. The principal safety outcome is major intracranial and extracranial bleeding; this is hypothesised to be increased in those randomised to take aspirin. The key consideration in then whether and to what extent the benefits of aspirin from the expected reduction in CVD events exceed the risks of major bleeding.

Discussion: this will be the first definitive trial of aspirin for primary CVD prevention in CKD patients. The research will be of great interest to clinicians, guideline groups and policy-makers, in the UK and globally, particularly given the high and rising prevalence of CKD that is driven by population aging and epidemics of obesity and diabetes. The low cost of aspirin means that a positive result would be of relevance to Low and Middle Income Countries and the impact in the developed world less diluted by any inequalities in health care access.
1745-6215
Gallagher, Hugh G.
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Dumbleton, Jennifer S.
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Maishman, Thomas
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Whitehead, Amy L
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Moore, Michael
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Fuat, Ahmet
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Fitzmaurice, David A.
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Henderson, Robert A.
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Lord, Joanne
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Griffith, Kathryn E
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Stevens, Paul
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Taal, Maarten W.
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Stevenson, Diane
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Fraser, Simon
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Lown, Mark
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Hawkey, Christopher J
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Roderick, Paul
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Gallagher, Hugh G.
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Dumbleton, Jennifer S.
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Maishman, Thomas
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Whitehead, Amy L
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Moore, Michael
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Fuat, Ahmet
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Fitzmaurice, David A.
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Henderson, Robert A.
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Lord, Joanne
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Griffith, Kathryn E
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Stevens, Paul
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Taal, Maarten W.
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Stevenson, Diane
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Fraser, Simon
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Lown, Mark
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Hawkey, Christopher J
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Roderick, Paul
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Gallagher, Hugh G., Dumbleton, Jennifer S., Maishman, Thomas, Whitehead, Amy L, Moore, Michael, Fuat, Ahmet, Fitzmaurice, David A., Henderson, Robert A., Lord, Joanne, Griffith, Kathryn E, Stevens, Paul, Taal, Maarten W., Stevenson, Diane, Fraser, Simon, Lown, Mark, Hawkey, Christopher J and Roderick, Paul (2022) Aspirin to target arterial events in chronic kidney disease (ATTACK): study protocol for a multicentre, prospective, randomised, open-label, blinded endpoint, parallel group trial of low-dose aspirin vs. standard care for the primary prevention of cardiovascular disease in people with chronic kidney disease. Trials, [331]. (doi:10.1186/s13063-022-06132-z).

Record type: Article

Abstract

Background: Chronic Kidney Disease (CKD) is a very common long-term condition and powerful risk factor for Cardiovascular Disease (CVD).
Low dose aspirin is of proven benefit in the secondary prevention of myocardial infarction (MI) and stroke in people with pre-existing CVD. However, in people without CVD the rates of MI and stroke are much lower, and the benefits of aspirin in the primary prevention of CVD are largely balanced by an increased risk of bleeding.
People with CKD are at greatly increased risk of CVD and so the absolute benefits of aspirin are likely to be greater than in lower risk groups, even if the relative benefits are the same. Post-hoc evidence suggests the relative benefits may be greater in the CKD population but the risk of bleeding may also be higher. A definitive study of aspirin for primary prevention in this high risk group, recommended by the National Institute for Health and Care Excellence (NICE) in 2014, has never been conducted. The question has global significance given the rising burden of CKD worldwide and the low cost of aspirin.

Methods: ATTACK is a pragmatic multicentre, prospective, randomised, open-label, blinded endpoint adjudication superiority trial of aspirin 75 mg daily vs. standard care for the primary prevention of CVD in 25,210 people aged 18 years and over with CKD recruited from UK Primary Care.
Participants aged 18 years and over with CKD (GFR category G1-G4) will be identified in Primary Care and followed up using routinely collected data and annual questionnaires for an average of 5 years. The primary outcome is the time to first major vascular event (composite of non-fatal MI, non-fatal stroke and cardiovascular death [excluding confirmed intracranial haemorrhage and other fatal cardiovascular haemorrhage]). Deaths from other causes (including fatal bleeding) will be treated as competing events. The study will continue until 1,827 major vascular events have occurred. The principal safety outcome is major intracranial and extracranial bleeding; this is hypothesised to be increased in those randomised to take aspirin. The key consideration in then whether and to what extent the benefits of aspirin from the expected reduction in CVD events exceed the risks of major bleeding.

Discussion: this will be the first definitive trial of aspirin for primary CVD prevention in CKD patients. The research will be of great interest to clinicians, guideline groups and policy-makers, in the UK and globally, particularly given the high and rising prevalence of CKD that is driven by population aging and epidemics of obesity and diabetes. The low cost of aspirin means that a positive result would be of relevance to Low and Middle Income Countries and the impact in the developed world less diluted by any inequalities in health care access.

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Accepted/In Press date: 28 February 2022
Published date: 21 April 2022

Identifiers

Local EPrints ID: 456194
URI: http://eprints.soton.ac.uk/id/eprint/456194
ISSN: 1745-6215
PURE UUID: 30143e54-d4da-4abc-a99a-e0c8519e33d2
ORCID for Michael Moore: ORCID iD orcid.org/0000-0002-5127-4509
ORCID for Joanne Lord: ORCID iD orcid.org/0000-0003-1086-1624
ORCID for Simon Fraser: ORCID iD orcid.org/0000-0002-4172-4406
ORCID for Mark Lown: ORCID iD orcid.org/0000-0001-8309-568X
ORCID for Paul Roderick: ORCID iD orcid.org/0000-0001-9475-6850

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Date deposited: 26 Apr 2022 16:44
Last modified: 28 Apr 2022 02:13

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Contributors

Author: Hugh G. Gallagher
Author: Jennifer S. Dumbleton
Author: Thomas Maishman
Author: Amy L Whitehead
Author: Michael Moore ORCID iD
Author: Ahmet Fuat
Author: David A. Fitzmaurice
Author: Robert A. Henderson
Author: Joanne Lord ORCID iD
Author: Kathryn E Griffith
Author: Paul Stevens
Author: Maarten W. Taal
Author: Diane Stevenson
Author: Simon Fraser ORCID iD
Author: Mark Lown ORCID iD
Author: Christopher J Hawkey
Author: Paul Roderick ORCID iD

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