CRD summary

The authors concluded that compared to mono antiplatelet therapy, dual antiplatelet therapy seemed to be safe and effective in the reduction of stroke and vascular event recurrence for patients with acute ischaemic stroke/transient ischaemic attack. They added that their findings needed to be confirmed in prospective studies. The authors' conclusions reflect the presented evidence and appear appropriate and reliable.

Authors' objectives

To asses the efficacy and safety of mono versus dual antiplatelet therapy used in patients with acute ischaemic stroke or transient ischaemic attack.

Searching

The Cochrane Library, MEDLINE and EMBASE were searched in April 2011 for potentially eligible studies. Search terms were reported. Existing reviews and reference lists of identified studies were searched. Studies were eligible regardless of publication status or language.

Study selection

Randomised controlled trials (RCTs) that compared mono versus dual antiplatelet therapy in non-cardioembolic ischaemic stroke or transient ischaemic attack were eligible for inclusion. Trials had to include patients over 18 years of age recruited within three days of stroke/transient ischaemic attack onset.

Most trials compared aspirin plus either clopidogrel or dipyridamole against aspirin alone. Dipyridamole and clopidogrel were also used as mono antiplatelet therapies. One study compared aspirin plus dipyridamole versus aspirin versus dipyridamole. Treatment duration (where reported) ranged from seven days to 42 months. Most studies included patients with both ischaemic stroke or transient ischaemic attack. Patient age (where reported) ranged from 55 to 69 years (measure not reported). The percentage of male patients (where reported) ranged from 53% to 78%.

Two authors selected studies for inclusion.

Assessment of study quality

The quality of trials was assessed for randomisation and allocation concealment. A trial was awarded A when it had true randomisation and concealed allocation and B where the randomisation process was not given and the concealment of allocation was unclear. Trials were also assessed on level of blinding, completeness of follow-up and intention-to-treat analysis.

Details of the quality assessment process were not reported.

Data extraction

Data were collected for the primary outcome of stroke recurrence (as defined in the trials) and a range of secondary outcomes (such as several composite outcomes, myocardial infarction, severe stroke, transient ischaemic attack, intracerebral haemorrhage, major bleeding and several death outcomes). Data were extracted to calculate relative risk (RR) with corresponding 95% confidence intervals (CIs)

Two authors independently extracted data. Discrepancies were resolved in discussion with a third author. Missing data were requested from the principal investigator of the respective trials.

Methods of synthesis

Data were synthesised using a random-effects meta-analysis. The Χ² and Ι² statistics were used to quantify heterogeneity. Funnel plots and Egger tests were used to assess publication bias.

Results of the review

Twelve RCTs were included in the review (3,766 participants, range 25 to 1,360). Ten trials were awarded A for true randomisation and concealed allocation. Six trials were reported as double-blind. Eight trials used intention-to-treat analyses. Loss to follow-up ranged from zero to 65.8%.

There was a significant reduction in stroke recurrence for dual antiplatelet therapy compared with mono antiplatelet therapy regardless of the drugs used (RR 0.67, 95% CI 0.49 to 0.93; 11 trials). There was no evidence of heterogeneity in this analysis (Ι²=0%). Using a funnel plot and the Egger test, the authors reported that there was no evidence of publication bias.

Dual antiplatelet therapy was associated with a significant reduction of composite vascular events (stroke, myocardial infarction, vascular death) (RR 0.75, 95% CI 0.56 to 0.99; 10 trials) and combined stroke, transient ischaemic attack and all death (RR 0.71, 95% CI 0.56 to 0.91; eight trials). No heterogeneity was found in any of these analyses. Findings of assessments of publication bias were not reported for these analyses.

Findings on major bleeding, poor functional outcome, fatal stroke, transient ischaemic attack, myocardial infarction, intracerebral haemorrhage, death and vascular death were non significant and there was no evidence of heterogeneity.

Authors' conclusions

Compared to mono antiplatelet therapy, dual antiplatelet therapy seemed to be safe and effective in the reduction of stroke and vascular event recurrence for patients with acute ischaemic stroke or transient ischaemic attack. These findings needed to be confirmed in prospective studies.

CRD commentary

The review question and inclusion criteria were clear. Relevant sources were searched comprehensively. The risk of missed studies seemed low as no language or publication status restrictions were placed on the search. The authors' assessments of publication bias indicated that this was not present for the primary outcome. The risk of publication bias for secondary outcomes was unclear. Use of independent and duplicate processes for study selection and data extraction reduces the risk of reviewer error and bias in these domains; it was unclear whether similar processes were in place for quality assessment.

The method of synthesis was appropriate and suitable measures were used to assess heterogeneity between studies. Appropriate domains were selected for quality assessment and results of the assessment were reported in detail. Methodological shortcomings of a small number of the individual studies (such as high loss to follow-up and lack of blinding) were not taken into consideration in the authors' discussion of their results and were not investigated using sensitivity analyses. The authors reported limitations of their review with regards to the arbitrarily chosen recruitment time frame of three days after the event and acknowledged possible variation between studies regarding the reporting of acute data for participants.

The authors' conclusions reflected the presented evidence, which was based on studies with small numbers of events. These cautious conclusions, which incorporated a need for further research, appear appropriate and reliable.

Implications of the review for practice and research

Practice: The authors acknowledged the exploratory nature of their research and recommended that no changes to practice be made based on their results.

Research: The authors recommended that prospective studies be conducted to confirm the findings of this review.

Funding

Not reported.

Bibliographic details

Geeganage CM, Diener HC, Algra A, Chen C, Topol EJ, Dengler R, Markus HS, Bath MW, Bath PM. Dual or mono antiplatelet therapy for patients with acute ischemic stroke or transient ischemic attack: systematic review and meta-analysis of randomized controlled trials. Stroke 2012; 43(4): 1058-1066. [PubMed: 22282894]

Original Paper URL

http://stroke.ahajournals.org/content/43/4/1058.abstract

Indexing Status

Subject indexing assigned by NLM

MeSH

Acute Coronary Syndrome /chemically induced /mortality; Adult; Aged; Aged, 80 and over; Aspirin /administration & dosage /adverse effects; Brain Ischemia /mortality /prevention & control; Databases, Factual; Dipyridamole /administration & dosage /adverse effects; Disease-Free Survival; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors /administration & dosage /adverse effects; Randomized Controlled Trials as Topic; Recurrence; Stroke; Survival Rate; Ticlopidine /administration & dosage /adverse effects /analogs & derivatives

AccessionNumber

12012020185

Database entry date

30/11/2012

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.