Is dipyridamole less liable than acetyl salicylic acid (ASA) to cause bleeding complications?/nA ni

Fråga: Is dipyridamole less liable than acetyl salicylic acid (ASA) to cause bleeding complications?

A ninety-year-old woman is medicating with ASA 75 mg/d for a previous episode of atrial fibrillation. Three months ago, she had a central venous thrombosis in one eye (she has earlier lost the vision of the other eye). Secondary to the thrombosis, there were retinal hemorrhages, and the ASA was seponated. Soon thereafter, she was prescribed Persantin (dipyridamole) 75 mg every 8 hours due to leg pain (no diagnosis of arterial insufficiency or thrombosis was made). There are persistent retinal bleedings, affecting her vision of sight.

Sammanfattning: In one large study, dipyridamole 400 mg/d did not differ from placebo regarding bleeding complications, while the frequency was twice as high in treatment with ASA 50 mg/d.

There are a few reports of hemorrhoidal bleedings and one pharyngeal hemorrhage during dipyridamole treatment, but the connection remains somewhat unclear. In Swedis, all reports of bleeding during dipyridamole treatment regarded patients simultaneously medicating with substances known to cause hemorrhage. The MPA states that the risk of bleeding during dipyridamole treatment is very low, and no evidence was found contradicting this statement.

Svar: Acetyl salicylic acid inhibits thrombocyte function by irreversible inactivation of platelet cyclooxygenase (1). Bleeding and easy bruising are well-known adverse effects of ASA (1). Dipyridamol inhibits thrombocyte function to some extent, by inhibiting phosphodiesterase and adenosine uptake (2).

In a randomised, placebo-controlled study (n=6602) comparing the secondary stroke preventive effects of ASA (50 mg/d) and dipyridamole (400 mg/d), the frequency of bleeding complications in dipyridamole treatment (4.7 per cent) did not differ from that in placebo (4.5 per cent) (3). In ASA treatment, on the other hand, the frequency was almost twice as high (8.2 per cent). Dipyridamole inhibits platelet aggregation to a small extent, but does not affect bleeding time, prothrombin time or partial thromboplastin time (4-5). According to a statement in a recent MPA workshop, the risk of bleeding complications in dipyramidol treatment is very small (4).

The Drugdex database mentions one case of pharyngeal bleeding and nineteen cases of hemorrhoidal bleedings in patients taking dipyridamole (5). In all cases, bleedings stopped after cessation of dipyridamole medication. No rechallenges were made.

In Swedis (Swedish Drug Information System), there are six reports of bleeding complications in patients taking dipyridamole (6). However, all those patients were simultaneously medicating with either warfarine or ASA. Consequently, it is not possible to link the hemorrhages to dipyridamole use. 1 Dollery C Sir, editor. Therapeutic drugs. 2nd ed. Edinburgh: Churchill Livingstone; 1999. p. A216-21 2 Dollery C Sir, editor. Therapeutic drugs. 2nd ed. Edinburgh: Churchill Livingstone; 1999. p. D161-4 3 Forbes CD et al: Secondary stroke prevention with low-dose aspirin, sustained release dipyridamole alone and in combination. Thromb Res 1998; 92: S1-S6 4 Behandlingsrekommedation Medical Product Agency. wwww.mpa.se/workshops/reko/trombos99_5.html 5 Drugdex: Dipyridamole 6 Swedis (The Swedish Drug Information System)