Infective Endocarditis and Antithrombotic Therapy

Abstract

Background: Incidence of infective endocarditis (IE) is progressively raising because of the increasing number of cardiovascular invasive procedures, support treatment and devices, awareness in the medical community, and improved diagnostic modalities. IE pathophysiology is a unique model of immunothrombosis, and the clinical course is often complicated by either embolic or hemorrhagic events. Managing antithrombotic treatment is challenging and the level of supporting evidence scant. The aim of this review was to discuss and present the embolic and bleeding complication associated with IE and review the available evidence on antithrombotic treatment in patients with IE with and without a previous indication to antithrombotic drugs.

Summary: Embolic events occur in 20-40% of patients with IE and are associated with high morbidity and mortality. Acute ischemic stroke is the most common neurological complication. A beneficial effect of antithrombotic therapy in preventing ischemic stroke for patients with IE has never been formally tested in adequately powered randomized clinical trials. Atrial fibrillation is a common complication associated with severe infections, requiring anticoagulation. Furthermore, patients with IE have a high risk of unprovoked and anticoagulation treatment-related bleeding. In particular, intracerebral bleeding is the most severe complication in about 5% of patients with IE. Single antiplatelet therapy with low-dose aspirin after hospitalization for IE has been shown to reduce causes mortality within 90 days without an increase of hemorrhagic strokes. In the absence of bleeding complications, recent guidelines recommend to maintain low-dose aspirin. No data are available on the management of patients with IE while on dual antiplatelet therapy.

Key messages: Several gaps in knowledge remain about antithrombotic management in patients with IE and most of the evidence relies on observational studies. Individualized strategies based on clinical evaluation, comorbidities, patient engagement, and shared decisions strategies are encouraged.

Keywords: Anticoagulant; Antiplatelet drugs; Bleeding complications; Infective endocarditis.

Fig. 1.

Schematic representation of the pathophysiology of aortic valve endocarditis, the most common clinical complications and the summary of the current recommendations in patients with preexisting indication to antithrombotic therapy. Upper panel: as result of invasive or semi-invasive procedures, some bacteria can access to the bloodstream and join directly to damaged or inflamed cardiac valve endothelium. The innate immune response is the first mechanism for host defense. Indeed, the infected endothelium switches into a prothrombotic state and express cytokines and chemokines involved in the recruitment and activation of platelets and leukocytes in the attempt to contain the infection. Activated platelets bind bacteria and boost neutrophil activation with neutrophil extracellular traps formation (NET). These innate immune cells together with killed bacteria (gray) components also promote the initiation of the coagulation cascade by activation of the extrinsic and intrinsic pathway. The exposure of tissue factor by monocytes, infected endothelial cell and by subendothelial matrix in cases of endothelial damages activates the coagulation extrinsic pathway. The intrinsic and extrinsic pathways converge in the common pathway that begins with the conversion of prothrombin into thrombin. Middle panel: the thrombin converts soluble fibrinogen into insoluble fibrin strands, which, on the one hand, act as a scaffold for platelets and white blood cells that fuel local inflammation and on the other hand prevent further bacterial spread by sealing off the infected tissue. Lower panel: emboli from the infected valve may reach the brain, spleen, myocardium, and the kidney as well as give rise to a mycotic aneurysm in different vascular beds. Treatment with oral anticoagulant drugs should be suspended at least during the first 2 weeks from the IE diagnosis, as the bleeding risk is high and because of possible the need of heart surgery. Antiplatelet therapy should be discussed on an individual basis.