Dipyridamole plus aspirin in cerebrovascular disease. 1999

J L Wilterdink, and J D Easton
Department of Neurology, Rhode Island Hospital, Providence 02903, USA.

BACKGROUND The second European Stroke Prevention Study (ESPS-2) recently reported a substantial benefit of dipyridamole combined with aspirin over aspirin alone in the prevention of stroke. This appears to be at odds with previous studies suggesting that dipyridamole adds nothing to aspirin alone. OBJECTIVE To review and compare the results of ESPS-2 and previous studies of dipyridamole plus aspirin and aggregate them in a meta-analysis. METHODS We combined the detailed data provided by the Antiplatelet Trialists' Collaboration on the previous studies of dipyridamole plus aspirin with the results from ESPS-2. The data on the previous trials were listed in the appendix of the 1994 publication of the Antiplatelet Trialists' Collaboration. RESULTS The results of our meta-analysis demonstrate that for the outcome of nonfatal stroke, ESPS-2 overwhelms previous data, which, even in the aggregate, did not include enough patients or outcome events to exclude efficacy for the combination of dipyridamole and aspirin. Differences between ESPS-2 and previous studies, which may have contributed to different results, include the doses and preparations of aspirin and dipyridamole. CONCLUSIONS The ESPS-2 showed that dipyridamole alone prevents stroke. More importantly, it showed a substantial benefit for dipyridamole combined with aspirin over aspirin alone. When the ESPS-2 data are aggregated with the 14 previous trials of dipyridamole combined with aspirin over aspirin alone, the combination reduces the risk of stroke by 23% over aspirin alone. Nevertheless, important questions remain unanswered. We conclude that another randomized clinical trial showing a significant benefit of the combination of dipyridamole plus aspirin over aspirin alone may be needed before the addition of dipyridamole to aspirin is widely accepted for prevention of stroke.

UI MeSH Term Description Entries
D010975 Platelet Aggregation Inhibitors Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system. Antiaggregants, Platelet,Antiplatelet Agent,Antiplatelet Agents,Antiplatelet Drug,Blood Platelet Aggregation Inhibitor,Blood Platelet Antagonist,Blood Platelet Antiaggregant,PAR-1 Antagonists,Platelet Aggregation Inhibitor,Platelet Antagonist,Platelet Antagonists,Platelet Antiaggregant,Platelet Antiaggregants,Platelet Inhibitor,Protease-Activated Receptor-1 Antagonists,Antiplatelet Drugs,Blood Platelet Aggregation Inhibitors,Blood Platelet Antagonists,Blood Platelet Antiaggregants,Platelet Inhibitors,Agent, Antiplatelet,Aggregation Inhibitor, Platelet,Antagonist, Blood Platelet,Antagonist, Platelet,Antiaggregant, Blood Platelet,Antiaggregant, Platelet,Drug, Antiplatelet,Inhibitor, Platelet,Inhibitor, Platelet Aggregation,PAR 1 Antagonists,Platelet Antagonist, Blood,Platelet Antiaggregant, Blood,Protease Activated Receptor 1 Antagonists
D002561 Cerebrovascular Disorders A spectrum of pathological conditions of impaired blood flow in the brain. They can involve vessels (ARTERIES or VEINS) in the CEREBRUM, the CEREBELLUM, and the BRAIN STEM. Major categories include INTRACRANIAL ARTERIOVENOUS MALFORMATIONS; BRAIN ISCHEMIA; CEREBRAL HEMORRHAGE; and others. Brain Vascular Disorders,Intracranial Vascular Disorders,Vascular Diseases, Intracranial,Cerebrovascular Diseases,Cerebrovascular Insufficiency,Cerebrovascular Occlusion,Brain Vascular Disorder,Cerebrovascular Disease,Cerebrovascular Disorder,Cerebrovascular Insufficiencies,Cerebrovascular Occlusions,Disease, Cerebrovascular,Diseases, Cerebrovascular,Insufficiencies, Cerebrovascular,Insufficiency, Cerebrovascular,Intracranial Vascular Disease,Intracranial Vascular Diseases,Intracranial Vascular Disorder,Occlusion, Cerebrovascular,Occlusions, Cerebrovascular,Vascular Disease, Intracranial,Vascular Disorder, Brain,Vascular Disorder, Intracranial,Vascular Disorders, Brain,Vascular Disorders, Intracranial
D002986 Clinical Trials as Topic Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries. Clinical Trial as Topic
D004176 Dipyridamole A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752) Antistenocardin,Apo-Dipyridamole,Cerebrovase,Cléridium,Curantil,Curantyl,Dipyramidole,Kurantil,Miosen,Novo-Dipiradol,Persantin,Persantine,Apo Dipyridamole,Novo Dipiradol
D004359 Drug Therapy, Combination Therapy with two or more separate preparations given for a combined effect. Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001241 Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5) Acetylsalicylic Acid,2-(Acetyloxy)benzoic Acid,Acetysal,Acylpyrin,Aloxiprimum,Colfarit,Dispril,Easprin,Ecotrin,Endosprin,Magnecyl,Micristin,Polopirin,Polopiryna,Solprin,Solupsan,Zorprin,Acid, Acetylsalicylic
D012306 Risk The probability that an event will occur. It encompasses a variety of measures of the probability of a generally unfavorable outcome. Relative Risk,Relative Risks,Risk, Relative,Risks,Risks, Relative
D014665 Vasodilator Agents Drugs used to cause dilation of the blood vessels. Vasoactive Antagonists,Vasodilator,Vasodilator Agent,Vasodilator Drug,Vasorelaxant,Vasodilator Drugs,Vasodilators,Vasorelaxants,Agent, Vasodilator,Agents, Vasodilator,Antagonists, Vasoactive,Drug, Vasodilator,Drugs, Vasodilator
D016017 Odds Ratio The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. Cross-Product Ratio,Risk Ratio,Relative Odds,Cross Product Ratio,Cross-Product Ratios,Odds Ratios,Odds, Relative,Ratio, Cross-Product,Ratio, Risk,Ratios, Cross-Product,Ratios, Risk,Risk Ratios

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