Theophylline, aminophylline, caffeine and analogues for acute ischaemic stroke

Theophylline and related drugs, which can enlarge brain blood vessels, are of no apparent benefit in the early treatment of strokes caused by blood clots. Most strokes are caused by a blood clot which then reduces blood flow in the affected part of the brain. Without an adequate blood supply, the brain quickly suffers damage which is often permanent. Drugs which can improve brain blood flow might reduce damage and improve outcome after stroke. Theophylline and related drugs have the ability to alter brain blood flow. This systematic review assesses whether this type of drug improves outcome after stroke. The review identified two small trials, neither of which found any benefit. The limited amount of data mean that there is no evidence at present to suggest that theophylline and related drugs should be used in acute stroke.

Authors' conclusions: 

There is not enough evidence to assess whether theophylline or its analogues, e.g. aminophylline, are safe and improve outcome in people with acute ischaemic stroke.

Read the full abstract...

Theophylline causes potent cerebral vasoconstriction which decreases blood flow in the non-ischaemic areas of the brain and increases collateral blood flow surrounding the ischaemic region. NOTE: This review covers an area where no active research is taking place. It will be updated if relevant information becomes available.


To assess the effect of theophylline and its analogues, aminophylline and caffeine, in people with confirmed or presumed acute ischaemic stroke.

Search strategy: 

We searched the Cochrane Stroke Group Trials Register (last searched November 2003). For the first version, we also searched EMBASE (1980 to 1999), MEDLINE (1966 to 1999) and Science Citation Index (1981 to 1999). We also contacted the principal investigators of the identified trials.

Selection criteria: 

Randomised trials of theophylline or an analogue compound compared with placebo or control in people with confirmed or presumed acute ischaemic stroke. Trials were included if treatment was started within one week of stroke onset.

Data collection and analysis: 

Three reviewer authors applied the inclusion criteria, assessed trial quality and extracted data for the first version. The review was updated by one review author.

Main results: 

Two trials involving just 119 patients were included; six studies were excluded. Trial quality was good. Both of the trials tested aminophylline. Analysis was by intention to treat where possible. No significant difference was shown in early case fatality (within four weeks) between aminophylline and placebo although the confidence intervals were wide (odds ratio (OR) 1.12, 95% confidence interval (CI) 0.49 to 2.56). There was no significant difference for early death and deterioration (OR 0.87, 95% CI 0.41 to 1.88). Death or disability was not significantly reduced by treatment based on 73 patients in one trial (OR 0.64, 95% CI 0.24 to 1.68). Data for late death and disability were not in a form suitable for analysis. No data on quality of life were available.