Long-term anticoagulant therapy in patients with coronary artery disease.

Secondary prevention of coronary events in coronary artery disease (CAD) patients with aspirin is generally accepted because of ease of administration, predictable safety, and proven efficacy. The use of long-term anticoagulant therapy with heparins, vitamin-K antagonists (VKAs), or thrombin inhibitors is, however, more controversial. During the last 40 years, several trials have been conducted in order to evaluate the role of anticoagulant therapy in patients with CAD as a protection against subsequent death and thrombo-embolic complications. The conducted trials are heterogeneous in many ways, concerning comparative medications, patient populations, endpoints and follow-up, which makes a standardized recommendation on the basis of these studies difficult. This review is an overview of the largest and best studies on this topic and discusses the scientific background for a possible use of VKA or an alternative anticoagulant treatment in CAD patients, looking at both the beneficial effects and the risk of bleeding.

Incomplete thromboxane inhibition with 100 mg of intravenous acetylsalicylic acid in patients with acute ST elevation myocardial infarction: a placebo-controlled pilot trial.

BACKGROUND: Acetylsalicylic acid (ASA) is now a standard treatment of acute myocardial infarction (AMI). ASA inhibits thromboxane A(2) (TXA(2)) production by blocking the constitutive cyclooxygenase (COX)-1 enzyme, but only to a small degree the inducible COX-2. COX-2 is induced by increased concentrations of cytokines, which is related to an enhanced inflammatory response. Previously, we have found a complete inhibition of TXA(2) synthesis in healthy volunteers after intravenous administration of 50 mg of ASA. We measured in a randomized, placebo-controlled pilot trial the effect of 100 mg of ASA injected intravenously on TXA(2) synthesis in AMI patients treated with streptokinase. METHODS AND RESULTS: Nineteen patients with AMI treated with streptokinase were randomized to 100 mg of ASA or placebo injected intravenously. Se-TXB(2) and bleeding time were measured before and after drug administration. One hundred and eighty minutes after intravenous ASA administration, treatment with oral ASA was initiated. We found a significant decrease in serum concentrations of TXB(2) after 30, 60 and 180 min following ASA injection compared to placebo, but in none of the patients was complete inhibition of TXA(2) production achieved. No significant change in bleeding time could be demonstrated. CONCLUSION: Intravenous ASA in a dosage of 100 mg did not completely prevent TXA(2) production in AMI patients treated with streptokinase. This may be due to synthesis of TXA(2) by the inducible COX-2 enzyme and/or to a transcellular metabolism in platelets of prostanoids generated by endothelial cells.