[Chronic ischemic cardiopathy: antiplatelet agents and anticoagulants, new protocols for prevention and treatment]. / Cardiopatia ischemica cronica: antiaggreganti ed anticoagulanti, nuovi regimi di profilassi e terapia.

The atherosclerotic process is negatively affected by all the components of the haemostatic system (vascular, platelets, blood coagulation, fibrinolysis). The diseased coronary tree is a high shear rate flow system which, in turn, implies a high number of platelet collisions at sites of vascular injury. This a distinctive feature of coronary thrombosis and illustrates the relevance of blood rheology in thrombosis development. It is appalling how the clinical benefit derived from a conceptually simple intervention such as the partial inhibition of platelet function or blood coagulation is actually discernible by a crude tool such as a clinical trial. Almost all the subgroups take advantage from the treatment and coronary as well as non-coronary events are prevented. Although strong arguments exist for the chronic use of oral anticoagulants in patients with previous myocardial infarction, antiplatelet regimens are more attractive because they do not require any particular skill and are unlikely to determine haemorrhagic complications. New strategies in the chronic antithrombotic treatment of patients with coronary atherosclerosis may involve the pharmacologic manipulation of GpIIb/IIIa (or other platelet integrins) as well as the direct blockade of thrombin. However it is the combination of different antithrombotic agents that appears most promising presently. The combined use of antiplatelet and anticoagulant drugs has already been shown to be effective in acute coronary syndromes and in patients with prosthetic heart valves. It is hoped that the same pattern will be confirmed also in the chronic phase of coronary artery disease by ongoing clinical trials.

Pharmacodynamic characteristics of low-molecular-weight dermatan sulphate after subcutaneous administration in acute myocardial infarction.

Sixteen patients (5 female and 11 male, mean age 59.1 years) who had had an acute myocardial infarction within the previous 7 days, were enrolled in an open pharmacodynamic study. Patients were randomly allocated to two treatment groups and given a single subcutaneous dose of 100 or 200 mg of a new low-molecular-weight dermatan sulphate. The drug pharmacodynamic profile was determined 1, 2, 4, 6, 8, 12 and 24 h after administration. The following coagulation and fibrinolysis tests were performed: activated partial thromboplastin time, thrombin time, activated factor X inhibition, Heptest (global clotting time), heparin cofactor II affinity, functional and antigenic plasminogen activator inhibitor and fibrin plate assay. Both Heptest and heparin cofactor II affinity were significantly increased (P < 0.001) in a dose-dependent manner. The XaI was enhanced, though to a lesser extent. None of the other coagulation or fibrinolysis tests showed significant changes at either dose. Systemic and local tolerance were always very good.

Benefit of adding low molecular weight heparin to the conventional treatment of stable angina pectoris. A double-blind, randomized, placebo-controlled trial.

BACKGROUND: Patients with chronic coronary artery disease exhibit a dysfunctioning endothelium, which may be responsible for exercise-induced platelet activation and expression of a procoagulant moiety. In this study, we evaluated the therapeutic efficacy of a low molecular weight heparin (Parnaparin) in patients with stable angina pectoris. METHODS AND RESULTS: According to a double-blind, randomized, placebo-controlled trial, 29 patients with stable exercise-induced angina pectoris and angiographically proven coronary artery disease received a single daily subcutaneous injection of Parnaparin or placebo on top of aspirin and conventional antianginal medication over 3 months. Patients randomized to Parnaparin showed a significant decrease in the fibrinogen level (P = .035) and an improvement in both the time to 1-mm ST segment depression (P = .008) and the peak ST segment depression (P = .015). The Canadian Cardiovascular Society class for angina pectoris was also improved by Parnaparin (P = .016). Parnaparin did not affect ADP and collagen-induced platelet aggregation, whereas thrombin-induced aggregation was reduced (P = .0001). The bleeding time was slightly prolonged, but this was not associated with any significant bleeding. CONCLUSIONS: Patients with stable angina pectoris may be treated with Parnaparin in addition to aspirin and conventional antianginal medication. Side effects are negligible, and compliance is excellent.

Comparison of efficacy of low molecular weight heparin (parnaparin) with that of unfractionated heparin in the presence of activated platelets in healthy subjects.

Arterial thrombosis is typically platelet-rich. In this study, it is shown that heparin levels resulting in the usual activated partial thromboplastin time therapeutic range provide only a small anticoagulant effect in the presence of activated platelets. Thrombin inhibition is also negligible when heparin is added to platelet-rich plasma. Aspirin improves the anticoagulant effect of heparin in these circumstances, but the degree of anticoagulation is still considerably lower than that observed in platelet-poor plasma. A low molecular weight heparin (parnaparin) is more active in the presence of activated platelets (such as may occur in acute coronary syndromes) regardless of whether aspirin is used concomitantly.