Combined anticoagulation and antiplatelet therapy for high-risk patients with atrial fibrillation: a systematic review

Authors: Lane D, Raichand S, Moore D, Connock M, Fry-Smith A, Fitzmaurice D

Journal: Health Technology Assessment Volume: 17 Issue: 30

Publication date: July 2013

DOI: 10.3310/hta17300

Citation:

Lane D, Raichand S, Moore D, Connock M, Fry-Smith A, Fitzmaurice D.Combined anticoagulation and antiplatelet therapy for high-risk patients with atrial fibrillation: a systematic review. Health Technol Assess 2013;17(30)


Download: Citation (for this publication as a .ris file) (456 Bytes)


Journal issues* can be purchased by completing the form.


The cost of reports varies according to number of pages and postage address. The minimum cost for a copy sent to a UK address is £30.00. We will contact you on receipt of your completed form to advise you of actual cost. If you have any queries, please contact nihredit@southampton.ac.uk.


*We regret that unfortunately we are unable to supply bound print copies of Health Technology Assessment published before issue 12:31. However, PDFs are available to print from the "Downloads" tab of the issue page.

Responses

No responses have been published. If you would like to submit a response to this publication, please do so using the form below.

Comments submitted to the NIHR Journals Library are electronic letters to the editor. They enable our readers to debate issues raised in research reports published in the Journals Library. We aim to post within 2 working days all responses that contribute substantially to the topic investigated, as determined by the Editors.

Your name and affiliations will be published with your comment.

Once published, you will not have the right to remove or edit your response. The Editors may add, remove, or edit comments at their absolute discretion.

Post your response

Surname

Forename

Middle Initial

Occupation / Job title

Affiliation / Employer

Email

Address

Other authors

For example, if you are responding as a team or group. Please ensure you include full names and separate these using commas

Statement of competing interests

We believe that readers should be aware of any competing interests (conflicts of interest).

The International Committee of Medical Journal Editors (ICMJE) define competing interests as including: financial relationships with industry (for example through employment, consultancies, stock, ownership, honoraria, and expert testimony), either directly or through immediate family; personal relationships; academic competition; and intellectual passion.

If yes, provide details below:

Enter response title

Enter response message

Enter CAPTCHA

Security key

Regenerate security key

By submitting your response, you are stating that you agree to the terms & conditions

The online version of this issue is currently unavailable.
The PDF version is available from the downloads section of this page.

Abstract

Background

Previous research suggests uncertainty whether or not there is any additional benefit in adding antiplatelet therapy (APT) to anticoagulation therapy (ACT) in patients with high-risk atrial fibrillation (AF) in terms of reduction in vascular events, including stroke. The existing guidelines acknowledge an increased risk of bleeding associated with such a strategy; however, there is no consensus on the treatment pathway.

Objectives

To determine, by undertaking a systematic review, if the addition of APT to ACT is beneficial compared with ACT alone in patients with AF who are considered to be at high risk of thromboembolic events (TEs).

Data sources

Data sources included bibliographic databases {the Cochrane Library [Cochrane Central Register of Controlled Trials (CENTRAL)], MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, ClinicalTrials.gov, National Institute for Health Research (NIHR) Clinical Research Network Portfolio, Current Controlled Trials (CCT) and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP)}, reference lists from identified systematic reviews and relevant studies, and contact with clinical experts. Searches were from inception to September 2010 and did not use language restrictions or study design filters.

Review methods

Studies of any design were included to evaluate clinical effectiveness, including randomised controlled trials (RCTs), non-randomised comparisons, cohort studies, case series or registries, longitudinal studies, systematic reviews and meta-analyses, and conference abstracts published after 2008. Inclusion criteria consisted of a population with AF, at high-risk of TEs, aged 18 years, on combined ACT and APT compared with others on ACT alone or ACT plus placebo. Inclusion decisions, assessment of study quality and data extraction were undertaken using methods to minimise bias.

Results

Fifty-three publications were included, reporting five RCTs (11 publications), 18 non-randomised comparisons (24 publications) and 18 publications that reported reviews, which added no further data. There was variation in the population, types and doses of ACT and APT, definitions of outcomes, and length of follow-up between the studies. There was a paucity of directly randomised high-quality RCTs, whereas non-randomised comparisons were found to have significant confounding factors. No studies looked at the effect of ACT plus APT compared with ACT alone on vascular events in patients with AF following acute coronary syndrome (ACS) or percutaneous coronary intervention. In most studies, significant differences in event rates were not seen between the patients on combined therapy compared with those on ACT alone for outcomes such as stroke (including haemorrhagic and ischaemic strokes), rates of transient ischaemic attacks, composite end points of stroke and systemic embolism (SE), SE alone, acute myocardial infarction, mortality (vascular or all cause) or bleeding events. There was conflicting evidence regarding rates of major adverse events consisting of composite end points, although event rates were generally low.

Limitations

An attempt was made to identify all of the available evidence around the subject despite the dearth of directly randomised studies using a robust review methodology. There was a paucity of directly randomised evidence to undertake a meta-analysis for the merits of one technology over another. The selection criteria were kept necessarily broad with regard to the population, intervention and comparator in order to capture all relevant studies.

Conclusions

This systematic review suggests that there is still insufficient evidence to advocate a clear benefit of the addition of APT to ACT compared with ACT alone in reducing the risk of vascular events in a population of patients at high risk of TEs resulting from AF. It is recommended that a definitive prospective RCT needs to be undertaken in a population at high risk of atherosclerotic coronary artery and other vascular events in addition to being at high risk of AF-mediated TEs. From the UK context, at the time of writing, any future trial should compare adjusted-dose warfarin [international normalised ratio (INR) 2.0-3.0] plus aspirin (75-325 mg) with adjusted-dose warfarin (INR 2.0-3.0). However, given the emergence of newer anticoagulation agents (dabigatran, rivaroxaban and apixaban) this prioritisation may need to be revisited in the future to reflect current best clinical practice.

Funding

The National Institute for Health Research Health Technology Assessment programme.

Publication updates

If you would like to receive information on publications and the latest news, click below to sign up.