It inhibits the enzyme adenosine deaminase which normally breaks down adenosine. This inhibition leads to increased levels of adenosine. Adenosine activates the enzyme adenylate cyclase which leads to increased cyclic AMP (cAMP) synthesis.
Dipyridamole also inhibits the enzyme phosphodiesterase which normally breaks down cAMP.

Both of these mechanisms lead to increased levels of cAMP within platelets. cAMP impairs platelet aggregation.

Modified release dipyridamole is used in conjunction with aspirin (Aggrenox®) in the secondary prevention of stroke and transient ischemic attack.

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Aggrenox
From OB/GYN News, 1/15/00 by Elizabeth Mechcatie

(aspirin/extended-release clipyridamole, Boehringer Ingelheim)

A combination of two antiplatelets for preventing stroke in people who have had a previous stroke or transient ischemic attack (TIA). This is the first antiplatelet combination studied as long-term preventive therapy in this population and the first product that combines two antiplatelet drugs in one.

* Recommended Dosage: One capsule containing 25 mg of aspirin and 200 mg of extended-release dipyridamole twice a day.

* Special Considerations: In studies, bleeding rates among Aggrenox-treated patients were similar to those treated with aspirin. About 5% more of treated patients had headaches than those on placebo.

European physicians have found that stopping treatment with Aggrenox for a few days, restarting treatment at one capsule a day and increasing to two a day after a few days has helped people who develop headaches with initial treatment, said Dr. Greg Albers, director of Stanford University's stroke center.

The extended-release dipyridamole formulation is not available separately The immediate-release formulation is available in smaller doses and the Food and Drug Administration indicates in the package insert that it should not be used with aspirin to substitute for Aggrenox, he noted.

* Comment: Approval was based on the results of the European Stroke Prevention Study 2 of over 6,000 people who had had an ischemic stroke or TIA within 3 months of the study.

Over 24 months, those treated with Aggrenox had a reduced risk of recurrent stroke that was 22% greater than those treated with 50 mg of aspirin a day alone, 24% greater than those on 400 mg/day extended release dipyridamole dose, and 37% greater than those on placebo.

Current guidelines for TIA and ischemic stroke prevention recommend aspirin as the first choice but refer to the three alternatives now available: Aggrenox, ticlopidine, and clopidogrel, said Dr. Albers, chair of the recently published guidelines on the prevention of stroke after TIA (Stroke 30[9]:1991-94, 1999).

These three drugs have never been directly compared, but data from separate studies that have compared them with aspirin suggest that Aggrenox may be more effective than clopidogrel, shown to reduce the risk of stroke 8% over aspirin alone, said Dr. Albers. Both have a good side effect profile, while ticlopidine, shown to reduce the risk of stroke 21% over aspirin alone, has some dangerous side effects in a small proportion of patients, he added.

Aspirin is considered the first choice because it is more cost effective than the others, which are more expensive, he added. Dr. Albers, professor of neurology at Stanford, has served on Boehringer Ingelheim's advisory board and has given lectures for the company but has no financial interests in the company.

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