Stroke. 2008;39:1397-1398
Published online before print February 14, 2008,
doi: 10.1161/STROKEAHA.107.499723
(Stroke. 2008;39:1397.)
© 2008 American Heart Association, Inc.
Dipyridamole for Preventing Stroke and Other Vascular Events in Patients With Vascular Disease
An Update
Els L.L.M. De Schryver, MD;
Ale Algra, MD
Jan van Gijn, MD, FRCP, FRCPE
From the Department of Neurology (E.L.L.M.D.S.), Rijnland Ziekenhuis Leiderdorp, the Netherlands; Julius Center for Health Sciences and Primary Care (A.A.), University Medical Center Utrecht, the Netherlands; Department of Neurology (A.A., J.v.G.), University Medical Center Utrecht, the Netherlands.
Correspondence to A. Algra, Julius Center for Health Sciences and Primary Care, mailbox STR 6.131, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, the Netherlands. E-mail A.Algra{at}umcutrecht.nl
Graeme J. Hankey MD, FRCP Section Editor:
Key Words: dipyridamole • prevention • review • stroke • vascular disease
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Introduction
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Patients with limited cerebral ischemia 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.
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Objectives
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To assess the efficacy and safety of dipyridamole versus control
in the secondary prevention of vascular events in patients with
vascular disease.
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Search Strategy
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We searched the Cochrane Stroke Group trials register (searched
June 2006), the Cochrane Central Register of Controlled Trials
(CENTRAL) (
The Cochrane Library Issue 2, 2006), MEDLINE (1966
to May 2006) and EMBASE (1980 to May 2006). We contacted authors
and pharmaceutical companies in the search for further data
on published and unpublished studies.
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Selection Criteria
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We selected randomized long-term secondary prevention trials
with concealed treatment allocation, treatment for >1 month,
starting within 6 months after presentation of an arterial vascular
disease. Treatment consisted of dipyridamole with or without
other antiplatelet drugs compared with no drug or an antiplatelet
drug other than dipyridamole.
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Data Collection and Analysis
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Two review authors independently selected trials for inclusion,
assessed trial quality and extracted data. Data were analyzed
according to the intention-to-treat principle.
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Main Results
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Twenty-nine trials were included (3 new since the previous review),
with 23 019 participants (previously 19 842), among whom 1503
vascular deaths and 3438 fatal and nonfatal vascular events
occurred during follow-up. Compared with control, dipyridamole
had no clear effect on vascular death (relative risk (RR) 0.99,
95% CI, 0.87 to 1.12). This result was not influenced by the
dose of dipyridamole or type of presenting vascular disease.
Compared with control, dipyridamole appeared to reduce the risk
of vascular events (
Figure, RR 0.88, 95% CI, 0.81 to 0.95).
On analysis per qualifying event, this effect was statistically
significant only in patients presenting with cerebral ischemia.
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Figure. Outcome vascular event (Figure 04.02.00. De Schryver ELLM, Algra A, van Gijn J. Dipyridamole for preventing stroke and other vascular events in patients with vascular disease [Cochrane review]. In: The Cochrane Library, Issue 3, 2007. Oxford: Update Software. MetaView © Update Software, Oxford.)
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Authors’ Conclusions
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For patients who present with arterial vascular disease, there
is no evidence that dipyridamole, in the presence or absence
of another antiplatelet drug (chiefly aspirin) reduces the risk
of vascular death, though it reduces the risk of further vascular
events. This benefit is found only in patients presenting after
cerebral ischemia. There is no evidence that dipyridamole alone
is more efficacious than aspirin.
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Implications for Practice
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Routine use of dipyridamole alone as first line antiplatelet
treatment in patients at high risk of vascular events is not
supported. Among patients presenting with arterial vascular
disease, especially ischemic stroke or transient ischemic attack,
the combination of dipyridamole plus aspirin is associated with
a lower risk of further vascular events than aspirin alone.
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Implications for Research
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More trials are needed in high-risk groups of patients other
than after ischemic stroke or transient ischemic attack, such
as those with arterial peripheral vascular disease, diabetic
retinopathy and patients undergoing hemodialysis to determine
the role of dipyridamole in secondary prevention. Also, trials
with aspirin plus extended release dipyridamole versus standard
treatment (clopidogrel, or clopidogrel plus aspirin—whichever
is the present standard) might be warranted in patients with
previous symptomatic atherothrombosis of the coronary arteries.
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Acknowledgments
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Disclosures
The authors are the principal investigators of ESPRIT, the European/Australian Stroke Prevention in Reversible Ischaemia Trial. The trial was run independently of any pharmaceutical company. The authors have received fees and expenses from producers of dipyridamole (Boehringer Ingelheim). After completion and full analysis of ESPRIT, we accepted financial support from Boehringer Ingelheim for post hoc exploratory analyses of the ESPRIT trial data, for which a contract was signed. These post hoc analyses pertain to the comparison of dipyridamole and aspirin versus aspirin alone; we negotiated complete scientific freedom in the contract. No money was received for any version of this review.
Received July 19, 2007;
accepted July 31, 2007.
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Introduction
Objectives