Risk of intracranial haemorrhage with bolus versus infusion thrombolytic therapy: a meta-analysis

Background Although thrombolytic therapy given by bolus injection seems to be as effective as infusion over 60-90 min, no single trial has been adequa tely powered to detect clinically important safety differences between the two strategies. We did a meta-analysis to find out whether bolus administra tion of thrombolytics is associated with an increased frequency of intracra nial haemorrhage, Methods We identified randomised trials comparing bolus with infusion throm bolytic therapy by a search of electronic databases, reference lists, and c onference proceedings. Odds ratios for primary intracranial haemorrhage, no n-haemorrhagic stroke, mortality, and reinfarction were calculated for each trial and were combined in a fixed-effects model. Findings Seven trials, involving a total of 103 972 patients, met our inclu sion criteria. Bolus treatment was associated with an increased risk of int racranial haemorrhage compared with infusion (0.8 vs 0.6%; odds ratio 1.25 [95% CI 1.08-1.45]; p=0.003). The increased risk was most striking in trial s comparing bolus with infusion administration of the same agent (1.75 [1.3 2-2.33], p=0.0001), but was also evident in trials comparing a newer-genera tion bolus agent with standard infusion therapy (1.25 [1.03-1.50]; p=0.02). The rates of non-haemorrhagic stroke (0.94 [0.81-1.09]), 30-day mortality (1.01 [0.97-1.06]), or reinfarction (1.04 [0.97-1.11]) did not differ betwe en the two strategies. Interpretation The increased risk of bolus thrombolytic treatment seems to be primarily associated with the method of administration rather than prope rties of the agents. Although the increased risk of intracranial haemorrhag e is small, physicians should balance this risk against the putative benefi ts of easier administration with no difference in mortality or reinfarction .