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Blood pressure-lowering treatment for the prevention of cardiovascular events in patients with atrial fibrillation: An individual participant data meta-analysis

Lookup NU author(s): Dr Dexter CanoyORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2021 Pinho-Gomes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background Randomised evidence on the efficacy of blood pressure (BP)-lowering treatment to reduce cardiovascular risk in patients with atrial fibrillation (AF) is limited. Therefore, this study aimed to compare the effects of BP-lowering drugs in patients with and without AF at baseline. Methods and findings The study was based on the resource provided by the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC), in which individual participant data (IPD) were extracted from trials with over 1,000 patient-years of follow-up in each arm, and that had randomly assigned patients to different classes of BP-lowering drugs, BP-lowering drugs versus placebo, or more versus less intensive BP-lowering regimens. For this study, only trials that had collected information on AF status at baseline were included. The effects of BP-lowering treatment on a composite endpoint of major cardiovascular events (stroke, ischaemic heart disease or heart failure) according to AF status at baseline were estimated using fixed-effect one-stage IPD meta-analyses based on Cox proportional hazards models stratified by trial. Furthermore, to assess whether the associations between the intensity of BP reduction and cardiovascular outcomes are similar in those with and without AF at baseline, we used a meta-regression. From the full BPLTTC database, 28 trials (145,653 participants) were excluded because AF status at baseline was uncertain or unavailable. A total of 22 trials were included with 188,570 patients, of whom 13,266 (7%) had AF at baseline. Risk of bias assessment showed that 20 trials were at low risk of bias and 2 trials at moderate risk. Meta-regression showed that relative risk reductions were proportional to trial-level intensity of BP lowering in patients with and without AF at baseline. Over 4.5 years of median follow-up, a 5-mm Hg systolic BP (SBP) reduction lowered the risk of major cardiovascular events both in patients with AF (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.83 to 1.00) and in patients without AF at baseline (HR 0.91, 95% CI 0.88 to 0.93), with no difference between subgroups. There was no evidence for heterogeneity of treatment effects by baseline SBP or drug class in patients with AF at baseline. The findings of this study need to be interpreted in light of its potential limitations, such as the limited number of trials, limitation in ascertaining AF cases due to the nature of the arrhythmia and measuring BP in patients with AF. Conclusions In this meta-analysis, we found that BP-lowering treatment reduces the risk of major cardiovascular events similarly in individuals with and without AF. Pharmacological BP lowering for prevention of cardiovascular events should be recommended in patients with AF.

Publication metadata

Author(s): Pinho-Gomes A-C, Azevedo L, Copland E, Canoy D, Nazarzadeh M, Ramakrishnan R, Berge E, Sundstrom J, Kotecha D, Woodward M, Teo K, Davis BR, Chalmers J, Pepine CJ, Rahimi K

Publication type: Article

Publication status: Published

Journal: PLoS Medicine

Year: 2021

Volume: 18

Issue: 6

Print publication date: 01/06/2021

Online publication date: 01/06/2021

Acceptance date: 25/03/2021

Date deposited: 25/11/2022

ISSN (print): 1549-1277

ISSN (electronic): 1549-1676

Publisher: Public Library of Science


DOI: 10.1371/journal.pmed.1003599

PubMed id: 34061831


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Funder referenceFunder name
British Heart Foundation “ACPG, KR & DC (grant number: FS/19/64/34673
KR & DC (grant number: PG/18/65/33872),
KR is also in receipt of funding from the UKRI’s Global Challenges Research Fund (Grant Ref ES/P011055/1),
MN, KR & DC (grant number FS/19/36/34346)
Oxford NIHR Biomedical Research Centre, and the Oxford Martin School at University of Oxford.