Aspirin and dipyridamole and their limitations in the therapy of coronary artery disease

Abstract

Summary:We have reviewed some of the voluminous literature on the effects of aspirin combined with dipyridamole on coronary thrombosis. There is clear evidence that aspirin is partially effective in preventing platelet aggregation and subsequent thrombosis in experimental constricted and damaged coronary arteries of dogs. Clinical studies show a clear reduction in myocardial infarction in male human subjects who are given aspirin as therapy for unstable angina, or as prophylaxis in asymptomatic individuals. In many studies aspirin and dipyridamole have been combined and are effective. We have not found dipyridamole to be effective in the dog with coronary artery constriction and find no substantial evidence that it is effective in preventing myocardial infarction in man. Until definitive studies show that combining dipyridamole with aspirin is more effective than aspirin alone, we do not recommend its use for prevention of coronary thrombosis. Experimental BackgroundIn an attempt to study the hemodynamic effects of chronic coronary artery constriction, a plastic cylinder was applied externally on the vessel so that it would induce narrowing of the coronary artery of a dog. Coronary blood flow in the constricted coronary artery was monitored by an electromagnetic flow meter. It was observed that, in many animals, there were periodic reductions in coronary blood flow followed by sudden resumption of normal flow.' This process repeated itself recurrently and frequently for several hours.Investigation of the mechanism of this cyclic reduction in coronary blood flow2 revealed that the coronary constrictor produced intimal damage, and that on this damaged, collagen-exposed surface, platelet aggregation precipitated the development of a thrombus. 3.4 This produced ever-increasing obstruction to coronary flow until the blood pressure gradient across the thrombus was sufficient to dislodge it. It then migrated down the coronary artery where it could be either diverted into a fixative and studied microscopically5 or permitted to embolize the distal coronary circulation. Microscopic study of these thrombi revealed masses of aggregated platelets, fibrin strands, and numerous damaged red blood cells.3 Doppler studies of blood flow in the femoral arteries of patients with known peripheral vascular disease showed transient reductions in flow similar to that shown in the dog constricted femoral and coronary artery.6 Transient ischemic attacks in patients with ulcerated atheromatous carotid disease are believed to be due to platelet and thrombus emboli to the since Fisher demonstrated aggregated platelet microemboli coursing through retinal arteries during episodes of amaurosis fugax.* Repetitive transient flow reductions were demonstrated to occur in the constricted and damaged femoral arteries of dogs and the carotid arteries of primate^.^.^ It appeared likely therefore that this process also occurred in human coronary and peripheral arteries when they were constricted by ulcerated or fissured atherosclerotic plaques.

Adenosine-mediated inhibition of platelet aggregation by acadesine. A novel antithrombotic mechanism in vitro and in vivo.

“…In contrast, human subjects that received 100 mg/kg acadesine over 90 min showed significant reductions in ex vivo platelet aggregation elicited by both ADP and collagen (Fig. 6) (9,44). In contrast, the present studies suggest that acadesine has a more pronounced activity that is evident even after administration to human subjects using an ex vivo assay, and where adenosine has a half-life in human blood of < 1 s (7).…”