Dipyridamole plus aspirin reduced the relative risk of stroke by about 20% compared to aspirin alone in patients at risk for secondary strokes.
The therapeutic benefits of dipyridamole in vascular disease and stroke prevention are likely mediated by its pleiotropic effects on the vascular wall, beyond simple platelet inhibition.
Effect estimate: RR 0.80
Dipyridamole (DP) is a phosphodiesterase inhibitor that increases the intracellular levels of cyclic adenosine monophosphate (cAMP) and cyclic guanine monophosphate (cGMP) by preventing their conversion to AMP and GMP, respectively. By increasing cAMP and cGMP levels in platelets, DP reversibly inhibits platelet aggregation and platelet-mediated thrombotic disease. In addition, DP may potentiate some of the vascular protective effects of endothelium-derived nitric oxide (NO), which increases cGMP by stimulating soluble guanylyl cyclase. Endothelium-derived NO is an important regulator of vascular tone, blood flow, and tissue perfusion. Indeed, endothelial NO synthase-deficient (eNOS −/− ) mice exhibit elevated systemic blood pressure and have larger myocardial and cerebral infarct size after ischemic injury. Other NO/cGMP-dependent effects that may be potentiated by DP include inhibition of vascular smooth muscle proliferation and prevention of endothelial-leukocyte interaction. In addition, DP increases local concentrations of adenosine and prostacyclin, which could affect vascular tone and inflammation. Finally, DP has antioxidant properties, which could stabilize platelet and vascular membranes as well as prevent the oxidation of low-density lipoprotein. These platelet and nonplatelet actions of DP may contribute to some of its therapeutic benefits in vascular disease.
Kim et al. (2008) studied ischemic stroke. dipyridamole plus aspirin vs. aspirin alone was evaluated on relative risk reduction of stroke (RR 0.80). Dipyridamole plus aspirin reduced the relative risk of stroke by about 20% compared to aspirin alone in patients at risk for secondary strokes.