This review found that dual-antiplatelet therapy lasting more than a year after ischaemic stroke or transient ischaemic attack was not associated with a greater reduction in overall recurrent stroke risk compared with aspirin or clopidogrel alone but it was linked to higher risk for intracranial haemorrhage than clopidogrel alone. The conclusions of this review appear to be reliable.

To examine the risk of recurrent stroke and intracranial haemorrhage linked to long-term dual- and single-antiplatelet therapy among patients with ischaemic stroke and transient ischaemic attack (TIA)

The authors searched PUBMED, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) up to March 2013 without language restrictions. Search terms were reported. Retrieved trials and a previous meta-analysis were examined to identify any additional trials.

Eligible studies needed to be randomised controlled trials (RCTs) involving patients with a history of ischaemic stroke or TIA. They needed to compare dual- and single-antiplatelet therapy and last at least one year. Studies where daily aspirin was used outside current recommended doses were excluded as were studies where more than 50% of participants had atrial fibrillation. Primary outcomes were association of dual- or single-antiplatelet therapy with risks for recurrent stroke and intracranial haemorrhage. Secondary outcomes were risk of ischaemic stroke, intracerebral haemorrhage, major vascular event, myocardial infarction, death, vascular death, major bleeding and major gastrointestinal bleeding.

From 63% to 72% of the participants in the included studies were men. Mean age of participants ranged from 63 to 67.1 years of age. Antiplatelet therapies included aspirin, clopidogrel, dipyridamole and ticlopidine. Treatment duration ranged from 1.3 to 3.5 years.

It was unclear how many reviewers were involved in the selection of studies for the review.

Study quality was assessed using the Cochrane risk of bias tool.

It appeared that two reviewers were involved in the assessment of quality of studies in the review.

Relative risks with 95% confidence intervals were calculated for recurrent stroke and intracranial haemorrhage with dual- and single-antiplatelet therapy and were based on intention-to-treat data.

All studies were data extracted by two researchers independently according to a standard protocol. Discrepancies were resolved by discussion with a third reviewer.

Results were stratified by comparator. A random-effects model of meta-analysis was used when two or more studies provided sufficient data for a given outcome. Statistical heterogeneity was assessed using the Χ² and Ι² statistics. Studies were deemed heterogeneous if the Χ² test was significant or Ι² was above 50%. Publication bias was assessed using funnel plots when 10 or more studies were available.

Seven RCTs (39,574 participants, range 270 to 20,332) were included in the review. The risk of bias in most of the included trials was low and the overall quality of evidence was moderate or high. The quality of the evidence was moderate among trials with aspirin as a comparator and high among trials with clopidogrel as a comparator.

Risk of recurrent stroke did not differ between patients who received dual-antiplatelet therapy and those who received aspirin therapy (RR 0.89, 95% CI 0.78 to 1.01; Ι²=57.2%; four trials) or clopidogrel monotherapy (RR 1.01, 95% CI 0.93 to 1.08; Ι²=0%; two trials).

Risk of intracranial haemorrhage did not differ between those who received dual-antiplatelet therapy and those who received aspirin therapy (RR 0.99, 95% CI 0.70 to 1.42; Ι²=20.5%; four trials). Patients who received dual-antiplatelet therapy were at greater risk of intracranial haemorrhage than those who received clopidogrel monotherapy (RR 1.46, 95% CI 1.17 to 1.82; Ι²=0%; two trials).

Results were reported for secondary outcomes.

Dual-antiplatelet therapy lasting more than a year after ischaemic stroke or TIA was not associated with a greater reduction in overall recurrent stroke risk than aspirin or clopidogrel monotherapy but it was linked to higher risk for intracranial haemorrhage than clopidogrel alone in the long term.

This review was based on defined inclusion criteria and was underpinned by a search of a range of resources. More than one reviewer was involved in extracting data for the review, which helps to minimise bias. Quality was assessed using a recognised tool and results presented in the context of their risk of bias. Meta-analysis appeared to be appropriate although there was variation between trials in antiplatelets given and significant statistical heterogeneity for one of the outcomes was not explored.

The conclusions of this review appear to be reliable.

Practice: The authors stated that long-term clopidogrel monotherapy may be a better choice than long-term dual antiplatelet therapy for secondary stroke prevention among patients with ischaemic stroke or TIA.

Research: The authors did not state any implications for research.

Chang Gung Memorial Hospital, Taiwan.

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.