Home > DARE Reviews > Dronedarone and the incidence of stroke...

PubMed Health. A service of the National Library of Medicine, National Institutes of Health.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Dronedarone and the incidence of stroke in patients with paroxysmal or persistent atrial fibrillation: a systematic review and meta-analysis of randomized trials

N Dagres, C Varounis, EK Iliodromitis, JP Lekakis, LS Rallidis, and M Anastasiou-Nana.

Review published: 2011.

Link to full article: [Journal publisher]

CRD summary

The review found evidence to indicate that dronedarone reduced the risk of stroke or transient ischaemic attack in individuals with paroxysmal or persistent atrial fibrillation, but more research was needed. These conclusions require some caution in interpretation due to lack of significant findings in the random-effects model and a lack of studies in which stroke was a prespecified outcome.

Authors' objectives

To evaluate the effects of dronedarone on the occurrence of stroke or transient ischaemic attack in individuals with paroxysmal or persistent atrial fibrillation (atrial fibrillation).

Searching

PubMed, EMBASE (from 1974) and Web of Knowledge were searched to April 2011. Search terms were reported. The proceedings of annual scientific meetings of the American Heart Association, Heart Rhythm Society, American College of Cardiology and European Society of Cardiology were searched to April/May 2011. Reference lists of retrieved articles were checked.

Study selection

Randomised controlled trials (RCTs) that compared dronedarone versus placebo in individuals with paroxysmal or persistent atrial fibrillation were eligible for inclusion. The primary review outcome was stroke or transient ischaemic attack during follow-up.

Participants in the included trials had paroxysmal or persistent atrial fibrillation or flutter and in one study they also had at least one additional risk factor (listed in the review). All the studies excluded individuals with permanent atrial fibrillation or advanced heart failure. One of the included RCTs, a dose-finding study, concluded that 400mgs twice daily was the optimal dose of dronedarone and in the other two RCTs all participants received this dose. In all the studies, stroke/transient ischaemic attack was recorded as an adverse event or as a reason for mortality or hospitalisation rather than as a prespecified outcome. Duration of follow-up ranged from six to 21 months.

Two reviewers independently selected the studies.

Assessment of study quality

The validity of the included studies was assessed using the Cochrane Risk of Bias tool to evaluate sequence generation, allocation concealment, blinding, incomplete outcome data and selective outcome reporting.

Two reviewers conducted the assessment.

Data extraction

Risk differences (RDs) between the two groups were calculated for each study, with 95% confidence intervals (CIs). Data were included only for participants who received a 400mg dose of dronedarone.

Two authors independently extracted the data.

Methods of synthesis

Studies were combined to calculate pooled risk differences and 95% CIs, using a fixed-effect and a random-effects method. Heterogeneity was assessed using the Χ² statistic. It was planned to investigate publication bias using the Begg and Egger tests if there were sufficient studies, but there were too few.

Results of the review

Four RCTs were included in the review (6,064 participants, 5,967 included in analysis; range 102 to 4,628). Two of the RCTs reported in a common publication and generated a single effect estimate. Overall the risk of bias was low (data not reported).

When a fixed-effect analysis was used, dronedarone was associated with a significantly lower risk of stroke or transient ischaemic attack than placebo, without heterogeneity (RD -0.0094, 95% CI -0.0178 to -0.0011; four RCTs, Χ² p=0.3). In this model one study, the ATHENA trial (4,628 participants), had 79.5% of the statistical weight.

When a random effects analysis was used, there was no significant difference between the groups (RD -0.0064, 95% CI -0.0144 to 0.0016; four RCTs,) and the ATHENA trial had 45.1% of the statistical weight and the combined EURIDIS/ADONIS trials (1,237 participants) had 50.5% of the statistical weight.

Authors' conclusions

There was a reduced risk of stroke or transient ischaemic attack in individuals with paroxysmal or persistent atrial fibrillation who received dronedarone. The evidence derived mostly from a single RCT and more research was needed.

CRD commentary

The objectives and inclusion criteria of the review were clear. Relevant sources were searched for studies, apparently without restriction by publication status. There were too few studies to assess for publication bias. It was unclear whether the search was limited by language. Appropriate steps were taken to limit the risk of reviewer bias in the processes of study selection, validity assessment and data extraction. Risk of bias was assessed using a suitable appropriate tool and overall risk was judged to be low. The quality characteristics of individual studies were not reported. It was not stated explicitly that the two RCTs reported in a combined article were clinically and statistically homogeneous.

The statistical methods used in the review to combine the studies and assess for heterogeneity were appropriate. The use of different statistical models usefully highlighted the dominance of a single RCT in the fixed-effect results and the need for further research.

The authors' conclusions require some caution in interpretation due to lack of significant findings in the random-effects model and a lack of studies in which stroke was a prespecified outcome.

Implications of the review for practice and research

Practice: The authors stated that a possible reduction in stroke risk in individuals with paroxysmal or persistent atrial fibrillation who received dronedarone would not effect their requirement for anticoagulation or other strategies to address cardiovascular risk factors.They stressed that the findings of this review did not apply to individuals with permanent atrial fibrillation.

Research: The authors stated that further research on the role of dronedarone in individuals with atrial fibrillation was needed.

Funding

No external funding.

Bibliographic details

Dagres N, Varounis C, Iliodromitis EK, Lekakis JP, Rallidis LS, Anastasiou-Nana M. Dronedarone and the incidence of stroke in patients with paroxysmal or persistent atrial fibrillation: a systematic review and meta-analysis of randomized trials. American Journal of Cardiovascular Drugs 2011; 11(6): 395-400. [PubMed: 22149318]

Indexing Status

Subject indexing assigned by NLM

MeSH

Amiodarone /analogs & derivatives /pharmacology; Anti-Arrhythmia Agents /pharmacology; Atrial Fibrillation /complications /drug therapy; Humans; Incidence; Ischemic Attack, Transient /etiology /prevention & control; Models, Statistical; Randomized Controlled Trials as Topic; Stroke /etiology /prevention & control

AccessionNumber

12012000163

Database entry date

28/05/2012

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 22149318

PubMed Health Blog...

read all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...