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Platelets play an integral role in primary hemostasis and in coronary atherothrombosis. Drugs such as aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDS), vitamin E, and COX-2 inhibitors such as celecoxib (Celebrex) affect platelet function. Antiplatelet drugs such as ticlopidine, clopidogrel, prasugrel, ticagrelor, cangrelor, and elinogrel inhibit the adenosine diphosphate receptors on the platelet surface. Other antiplatelet drugs such as abciximab, eptifibatide, and tirofiban, by inhibiting the glycoprotein IIb/IIIa receptors, inhibit the final common pathway of platelet aggregation. Vorapaxar and atopaxar inhibit PAR1 thrombin receptor-activating peptide (TRAP)-induced platelet aggregation. Given the several agonists involved in different pathways of platelet aggregation, the combination of two antiplatelet drugs may be quite a rational approach in order to boost antithrombotic efficacy. Caution is needed in selecting the types of antiplatelet drugs as a combination therapy and their respective dosages in order to avoid serious bleeding complications. Several tests for monitoring antiplatelet drugs are available. The search for an ideal antiplatelet drug and also an ideal test for monitoring its effects continue.

Peripheral artery disease (PAD) is a term that relates to atherosclerosis and narrowing of the arteries in the lower extremities. The prevalence of PAD is approximately 12% of the adult population. Despite the low rate of peripheral complications and amputation, PAD is complicated by a high rate of cardiovascular events including myocardial infarction, stroke, and vascular death with an annual incidence of about 5%.

With the growing complexity of vascular interventional radiology, a larger array of drug treatments is employed by practitioners undertaking these procedures. Furthermore, patients attending for treatment are likely to be on combinations of drugs which may interact with medications employed during endovascular procedures. This chapter describes the mechanisms of action of drugs commonly used in this patient group and illustrates the likely interactions that may be encountered during endovascular procedures.

Blood platelet activation at the contact of an injured vessel wall results in adhesion, shape change, aggregation and secretion, which are all tightly regulated biological processes to fulfill the main physiological function of platelets: the arrest of bleeding or primary hemostasis. The same mechanisms of activation are triggered when platelets encounter an atherosclerotic plaque rupturing or following mechanical or infectious injury of the vessel wall, resulting in arterial thrombosis or disseminated intravascular thrombosis. Knowledge of the molecular biology of hemostasis has increased considerably during the last few decades due to the accurate observation of defective hemostasis in patients exhibiting selective abnormalities in platelet surface glycoproteins involved in adhesive functions, defects of plasma adhesive proteins, or defects affecting the complex network of receptors and their transduction machinery. The era of gene targeting and transgenesis in living animals has largely confirmed previous knowledge about the molecular aspects of platelet functions. New insights have also emerged with the perspective of identifying as-yet-unexpected targets for antiplatelet drugs. Blood platelets of transgenic mice have been studied not only to explore hemostasis and thrombosis but also for purposes of general biochemistry and molecular biology. This accounts for the broad range of targeted genes resulting in platelet dysfunction, not all being relevant to pharmacological objectives in terms of antiplatelet drug research. However, these transgenic mice have greatly improved our general understanding of platelet physiology and represent useful models for preclinical pharmacology and basic science.

Graft occlusion remains the most important adverse event after coronary artery bypass graft (CABG) surgery. Occlusion rates increase from 10%– 15% per distal anastomosis in the first month to approximately 16%–26% at 1 year, averaging 37% at 5–7 years and 55% at 10–12 years [1, 2]. A recent study reported graft disease in 8% at 1 year, 38% at 5 years, and 75% at 10 years postoperatively [3]. The pathogenesis of vein graft occlusion appears to have some similarities with the development and progression of atherosclerosis, which is discussed by Jang and Fuster (this volume). Drug therapy should therefore be aimed at intervening in this pathogenesis. Since platelet deposition is an early factor in the occlusive process, platelet inhibitors play an important role here. Anticoagulants, on the other hand, are potent drugs to prevent arterial thrombus formation. These two groups of drugs have therefore been used during the past decade to prevent vein graft occlusion.

Platelet interactions with vessel wall are certainly important in the pathophysiology of myocardial ischemia [1]. Interventions that reduce platelet reactivity (adhesion, aggregation, release/secretion) have been performed in the last two decades for several clinical forms of ischemic heart disease. This brief review will deal only with aspirin, which is the antiplatelet drug more and better studied in this context, and is still the most used in clinical practice [2].

Children with congenital cyanotic heart disease are prone to hemorrhagic as well as thrombo-embolic complications. Formerly it has been suggested that the alterations of the hemodynamics existing in this kind of disease caused continuous disseminated intravascular coagulation with consumption coagulopathy. More recent kinetic studies however showed that in cyanotic heart disease only the survival time of the thrombocytes is shortened while the fibrinogen consumption is normal (1, 3, 4). From the aspect of coagulation physiology we have a similar situation in the hemolytic uremic syndrome. Therefore we treat patients with hemolytic uremic syndrome not with anticoagulants but with antiplatelet drugs, in order to interrupt the vicious circle platelet induced thrombosis platelet → consumption → thrombocytic bleeding tendency (2). Best results were obtained with the combination of ASA (Aspirin) and Dipyridamol (Persantin) (1). The following is a report of our preliminary experiences with antiplatelet therapy in children with congenital cyanotic heart disease.

Considering the benefits of platelet-antiaggregation therapy following PTA, three phases must be distinguished: 1. Phase one refers to the time about and immediately after the intervention, that is the first hours and first days after PTA. 2. Phase two applies to the months following the PTA. 3. Late phase refers to the period beginning 6 months to 1 year after PTA.

Antiplatelet drug regimens are currently used to reduce intimai hyperplasia (IH) and improve long-term vein graft patency following arterial reconstruction. Ninety-six autologous external jugular vein grafts were implanted between bilaterally divided femoral arteries in 48 dogs. The animals received a 2% cholesterol diet and antiplatelet drug regimens 1 week before and for 6 weeks following operation. Ten control animals (CON) received the diet alone, 10 dogs received Persantine (dipyridamole), 2.5 mg/kg, and 325 g aspirin (PASA), 11 dogs received cod-liver oil containing 1.8 g eicosapentaenoic acid (EPA) daily, and a further 17 dogs received 1.8 g EPA and 2.5 mg/kg Persantine daily (EPA-P). Prothrombin time (PT), partial thromboplastin time (PTT), bleeding times (BTS), and platelet counts (PTLS) were measured before operation and during antiplatelet therapy. Vein grafts were havested at 6 weeks and intimal thickness was measured with a Zeiss computerized microscope. The intima measured 6.1 ± 0.2 pm prior to implantation and increased to 78 ± 8 µm in the CON. P-ASA decreased IH to 33 ± 3 µm (P < 0.001), EPA decreased IH to 27 ± 3 µm (P < 0.001), and EPA-P reduced IH to 17 ± 1 µm (P < 0.001). PTL decreased in the P-ASA group (P < 0.05) and BT decreased in the EPA-P group (P < 0.05) but all other coagulation parameters were unchanged. Although all antiplatelet regimes reduced IH, EPA-P was the most effective (P < 0.009).