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 1827 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 is 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 ageing 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. Trial registration: ISRCTN: ISRCTN40920200. EudraCT: 2018-000644-26. ClinicalTrials.gov: NCT03796156.
Aspirin, Cardiovascular disease, Chronic kidney disease, Primary care, Primary prevention
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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21 April 2022
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, 23 (1), [331].
(doi:10.1186/s13063-022-06132-z).
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 1827 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 is 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 ageing 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. Trial registration: ISRCTN: ISRCTN40920200. EudraCT: 2018-000644-26. ClinicalTrials.gov: NCT03796156.
Text
Protocol paper - accepted version
- Accepted Manuscript
Text
s13063-022-06132-z
- Version of Record
More information
Accepted/In Press date: 28 February 2022
e-pub ahead of print date: 21 April 2022
Published date: 21 April 2022
Additional Information:
Funding Information:
ATTACK is jointly funded by the National Institute for Health Research Health Technology Assessment Programme (HTA Project: 16/31/127) and the British Heart Foundation (Ref: SP/17/14/33355). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.
Funding Information:
ATTACK is sponsored by the University of Southampton, Research and Innovation Services, George Thomas Building 37 Room 4079, University Road, Highfield, Southampton, SO17 1BJ. The final trial Protocol was reviewed and approved by the Sponsor. The Sponsor (and Funders) will not have any direct role in the collection, management, analysis and interpretation of data, or the writing of the report, nor will either have ultimate authority over these activities; however, the Sponsor will have oversight of all aspects of the trial, as required by clinical trial regulations.
Funding Information:
ATTACK is jointly funded the National Institute for Health Research Health Technology Assessment Programme (HTA Project: 16/31/127) and the British Heart Foundation (Ref: SP/17/14/33355). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.
Publisher Copyright:
© 2022, The Author(s).
Keywords:
Aspirin, Cardiovascular disease, Chronic kidney disease, Primary care, Primary prevention
Identifiers
Local EPrints ID: 456194
URI: http://eprints.soton.ac.uk/id/eprint/456194
ISSN: 1745-6215
PURE UUID: 30143e54-d4da-4abc-a99a-e0c8519e33d2
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Date deposited: 26 Apr 2022 16:44
Last modified: 28 Aug 2024 01:48
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Contributors
Author:
Hugh G. Gallagher
Author:
Jennifer S. Dumbleton
Author:
Thomas Maishman
Author:
Ahmet Fuat
Author:
David A. Fitzmaurice
Author:
Robert A. Henderson
Author:
Kathryn E Griffith
Author:
Paul Stevens
Author:
Maarten W. Taal
Author:
Diane Stevenson
Author:
Christopher J Hawkey
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