Anithrombotic prevention in vascular disease: bases for a new strategy in antithrombotic therapy

Abstract

A tendency toward bleeding often undercuts the beneficial preventive effect of higher doses of a single antithrombotic drug or combined antithrombotic therapy. Although high doses of antithrombotic drugs may be necessary for optimal prevention, such therapy can also elicit more frequent bleeding. Although major bleeding could be a reversible event is likely to lead clinicians to discontinue antithrombotic therapy which in turn could increase the risk of myocardial infarction, stroke, and cardiovascular death. Thus, to prevent thrombotic events without frequent bleeding complications, the preferred approach might be to use anti-inflammatory drugs in addition to the first-line antithrombotic drugs to reduce inflammation and thrombin formation in atheroma. Although some preliminary data have been already published, to confirm the potential benefit of anti-inflammatory drugs in acute coronary syndromes large prospective double-bind randomized trials are necessary.

Figure 1

Thrombin generation in a disrupted atheroma. After plaque rupture, local inflammation leads to exposure of TF to the surrounding blood, initiating thrombin generation. Activated platelets release active components from the cytosol, which induces the externalization of phosphatidylserine through the flip-flop mechanism. Platelets exerts a regulatory function by serving as a source of inflammatory mediators and interacting with circulating white cells. Local blood flow changes in the culprit artery increase in situ prothrombotic conditions. Local fibrinolysis release thrombin-bound fibrin and contribute to thrombus growth.

Figure 2

Reducing inflammation with anti-inflammatory drugs and lower doses of standard therapies (heparin, aspirin, clopidogrel, and/or new antithrombotic drugs, prasugrel, dabigatran, rivaroxaban) could diminish thrombin formation and prevent thrombus growth with less frequent bleeding. This represents a possible alternative to current antithrombotic therapy offering similar efficacy and less bleeding complications.