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Allopurinol versus usual care in UK patients with ischaemic heart disease (ALL-HEART): a multicentre, prospective, randomised, open-label, blinded-endpoint trial

Mackenzie, Isla S; Hawkey, Christopher J; Ford, Ian; Greenlaw, Nicola; Pigazzani, Filippo; Rogers, Amy; Struthers, Allan D; Begg, Alan G; Wei, Li; Avery, Anthony J; Taggar, Jaspal S; Walker, Andrew; Duce, Suzanne L; Barr, Rebecca J; Dumbleton, Jennifer S; Rooke, Evelien D; Townend, Jonathan N; Ritchie, Lewis D; MacDonald, Thomas M

Allopurinol versus usual care in UK patients with ischaemic heart disease (ALL-HEART): a multicentre, prospective, randomised, open-label, blinded-endpoint trial Thumbnail


Authors

Isla S Mackenzie

Christopher J Hawkey

Ian Ford

Nicola Greenlaw

Filippo Pigazzani

Amy Rogers

Allan D Struthers

Alan G Begg

Li Wei

Dr JASPAL TAGGAR JASPAL.TAGGAR@NOTTINGHAM.AC.UK
Professor of Primary Care and Medical Education

Andrew Walker

Suzanne L Duce

Rebecca J Barr

Jennifer S Dumbleton

Evelien D Rooke

Jonathan N Townend

Lewis D Ritchie

Thomas M MacDonald



Abstract

Background: Allopurinol is a urate-lowering therapy used to treat patients with gout. Previous studies have shown that allopurinol has positive effects on several cardiovascular parameters. The ALL-HEART study aimed to determine whether allopurinol therapy improves major cardiovascular outcomes in patients with ischaemic heart disease. Methods: ALL-HEART was a multicentre, prospective, randomised, open-label, blinded-endpoint trial done in 18 regional centres in England and Scotland, with patients recruited from 424 primary care practices. Eligible patients were aged 60 years or older, with ischaemic heart disease but no history of gout. Participants were randomly assigned (1:1), using a central web-based randomisation system accessed via a web-based application or an interactive voice response system, to receive oral allopurinol up-titrated to a dose of 600 mg daily (300 mg daily in participants with moderate renal impairment at baseline) or to continue usual care. The primary outcome was the composite cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death. The hazard ratio (allopurinol vs usual care) in a Cox proportional hazards model was assessed for superiority in a modified intention-to-treat analysis (excluding randomly assigned patients later found to have met one of the exclusion criteria). The safety analysis population included all patients in the modified intention-to-treat usual care group and those who took at least one dose of randomised medication in the allopurinol group. This study is registered with the EU Clinical Trials Register, EudraCT 2013-003559-39, and ISRCTN, ISRCTN32017426. Findings: Between Feb 7, 2014, and Oct 2, 2017, 5937 participants were enrolled and then randomly assigned to receive allopurinol or usual care. After exclusion of 216 patients after randomisation, 5721 participants (mean age 72·0 years [SD 6·8], 4321 [75·5%] males, and 5676 [99·2%] white) were included in the modified intention-to-treat population, with 2853 in the allopurinol group and 2868 in the usual care group. Mean follow-up time in the study was 4·8 years (1·5). There was no evidence of a difference between the randomised treatment groups in the rates of the primary endpoint. 314 (11·0%) participants in the allopurinol group (2·47 events per 100 patient-years) and 325 (11·3%) in the usual care group (2·37 events per 100 patient-years) had a primary endpoint (hazard ratio [HR] 1·04 [95% CI 0·89–1·21], p=0·65). 288 (10·1%) participants in the allopurinol group and 303 (10·6%) participants in the usual care group died from any cause (HR 1·02 [95% CI 0·87–1·20], p=0·77). Interpretation: In this large, randomised clinical trial in patients aged 60 years or older with ischaemic heart disease but no history of gout, there was no difference in the primary outcome of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death between participants randomised to allopurinol therapy and those randomised to usual care. Funding: UK National Institute for Health and Care Research.

Citation

Mackenzie, I. S., Hawkey, C. J., Ford, I., Greenlaw, N., Pigazzani, F., Rogers, A., …MacDonald, T. M. (2022). Allopurinol versus usual care in UK patients with ischaemic heart disease (ALL-HEART): a multicentre, prospective, randomised, open-label, blinded-endpoint trial. Lancet, 400(10359), 1195-1205. https://doi.org/10.1016/S0140-6736%2822%2901657-9

Journal Article Type Article
Acceptance Date Aug 23, 2022
Online Publication Date Oct 7, 2022
Publication Date Oct 8, 2022
Deposit Date Nov 10, 2022
Publicly Available Date Mar 29, 2024
Journal The Lancet
Print ISSN 0140-6736
Electronic ISSN 1474-547X
Peer Reviewed Peer Reviewed
Volume 400
Issue 10359
Pages 1195-1205
DOI https://doi.org/10.1016/S0140-6736%2822%2901657-9
Keywords Treatment Outcome, Coronary Artery Disease - drug therapy, Aged, Prospective Studies, Myocardial Infarction - drug therapy, Male, Female, Allopurinol - therapeutic use, Uric Acid, Myocardial Ischemia - drug therapy, Stroke - drug therapy, Gout - drug ther
Public URL https://nottingham-repository.worktribe.com/output/13165875
Publisher URL https://www.sciencedirect.com/science/article/pii/S0140673622016579?via%3Dihub

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