This review found that short-term use of antifibrinolytic therapy associated with medical prevention of ischaemic deficit decreased the risk of re-bleeding without increasing the risk of cerebral infarction. This review has some limitations and the conclusions seem overstated given that the short-term results are based on a subgroup of two studies of unclear quality.

To assess the impact of antifibrinolytic therapy in the management of aneurysmal subarachnoid haemorrhage on functional outcome, re-bleeding and delayed ischaemic events.

PubMed was searched to December 2010 for studies published in English. Search terms were reported. Reference lists of papers were searched.

Eligible studies were prospective or retrospective studies that compared antifibrinolytic treatment with control treatment in adults with aneurysmal subarachnoid haemorrhage and reported at least one of the outcomes: poor functional outcome at the study end (death, vegetative state or severe disability), re-bleeding and reported cerebral ischaemia.

Two-thirds of the included studies assessed tranexamic acid and the rest assessed 6-aminocaproic acid. Three studies used calcium channel blockers. Most studies were of long-term therapy (more than 72 hours). Two studies were of short-term therapy (given for less than 72 hours after diagnosis). Studies were grouped as: long-term antifibrinolytic therapy and no medical prevention of ischaemic deficit; long-term antifibrinolytic therapy with medical prevention of ischaemic deficit; and short-term antifibrinolytic therapy with medical prevention of ischaemic deficit.

Two reviewers independently selected studies. Disagreements were resolved by consensus.

The authors did not state that they assessed study quality.

Odds ratios (OR) with 95% confidence intervals (CI) were calculated for dichotomous outcomes (such as poor functional state).

Two reviewers independently extracted data. Disagreements were resolved by consensus.

Studies were pooled using the Peto fixed-effects model. Heterogeneity was assessed using the Χ² test and Ι² statistic. Where heterogeneity was statistically significant (p<0.10 and Ι²>50%) a random-effects model was used for the pooling. Subgroup analyses were used to compare the different types of treatment.

Seventeen studies (2,872 patients, range 46 to 505; 1,380 patients received antifibrinolytic therapy) were included: 12 studies were randomised controlled trials (RCTs), three were prospective observational and two were retrospective observational studies.

Overall no significant difference was seen between antifibrinolytic therapy and control for functional outcome (five studies). No differences were seen in any of the three subgroups based on duration and type of treatment, but short-term treatment reduced the numbers of poor outcomes (29% versus 37.8%) and long-term treatment appeared to increase them. None of these results were statistically significant.

Antifibrinolytic therapy significantly reduced rates of re-bleeding compared to controls (OR 0.48, 95% CI 0.30 to 0.76; 15 studies with Ι²=72%). Similar results were seen for all three subgroups. Antifibrinolytic therapy significantly increased rates of cerebral infarction (OR 1.27, 95% CI 1.05 to 1.54; nine studies with Ι²=39%). The only subgroup showing a similar increase was long-term therapy with no medical prevention (OR 1.90, 95% CI 1.37 to 2.64; six studies with Ι²=0%).

The short-term use of antifibrinolytic therapy associated with medical prevention of ischaemic deficit decreases the risk of re-bleeding and does not increase the risk of cerebral infarction, therefore potentially giving better protection against poor functional outcome.

This review had clear inclusion criteria for intervention, participants and outcomes. All study designs were eligible. The literature search was limited to one database and studies published in English so there was a high risk of publication bias (acknowledged by the authors). Studies were selected and data were extracted by two independent reviewers to reduce the chance of reviewer bias or error. It appeared that study quality was not assessed. Studies were pooled using meta-analysis. Subgroup analyses were used to compare three groups of antifibrinolytic therapy.

This review had some limitations and the authors' conclusions seem overstated given that the short-term results were based on a subgroup of two studies of unclear quality. However, the authors stated that their results should be seen as hypothesis-generating rather than supporting.

The authors did not make any recommendations for practice.

Research: The authors stated that a new randomised trial of antifibrinolytic therapy was needed.

None.