Dipyridamole for preventing stroke and other vascular events in patients with vascular disease

Patients with limited cerebral ischaemia of arterial origin are at risk of serious vascular events (4% to 11% annually). Aspirin reduces that risk by 13%. In one trial, adding dipyridamole to aspirin was associated with a 22% risk-reduction compared with aspirin alone. However, a systematic review of all trials of antiplatelet agents by the Antithrombotic Trialists' Collaboration showed that, in high-risk patients, there was virtually no difference between the aspirin-dipyridamole combination and aspirin alone.

To assess the efficacy and safety of dipyridamole versus control in the secondary prevention of vascular events in patients with vascular disease.

We searched the Cochrane Stroke Group trials register (searched November 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005), MEDLINE (1966 to November 2005) and EMBASE (1980 to November 2005).

Randomised long-term secondary prevention trials with concealed treatment allocation, treatment for more than one month, starting within six months after presentation of an arterial vascular disease were selected. Treatment consisted of dipyridamole with or without other antiplatelet drugs compared with no drug or an antiplatelet drug other than dipyridamole.

Two authors independently selected trials for inclusion, assessed trial quality and extracted data. Data were analysed according to the intention-to-treat principle.

Twenty-seven trials were included, with 20242 patients, among whom 1399 vascular deaths and 3090 fatal and non-fatal vascular events occurred during follow up. Compared with control, dipyridamole had no clear effect on vascular death (relative risk (RR) 1.02, 95% confidence internal (CI) 0.90 to 1.17). This result was not influenced by the dose of dipyridamole or type of presenting vascular disease. In the presence of aspirin, dipyridamole appeared to reduce the risk of vascular events compared with control (RR 0.90, 95% CI 0.82 to 0.97), due to a single large trial in patients presenting with cerebral ischaemia.

For patients who presented with arterial vascular disease, there was no evidence that dipyridamole, in the presence or absence of another antiplatelet drug reduced the risk of vascular death, though it may reduce the risk of further vascular events. However, this benefit was found in only one single large trial and only in patients presenting after cerebral ischaemia. There was no evidence that dipyridamole alone was more efficacious than aspirin. Further trials comparing the effects of the combination of dipyridamole with aspirin versus aspirin alone are justified.