Can patients with infectious endocarditis be safely anticoagulated?

How great is the benefit or the potential harm?

Some experts argue that the incidence of ischemic stroke with hemorrhagic transformation in patients with infectious endocarditis receiving anticoagulation is overestimated. According to this view, the beneficial effects of anticoagulation at least counterbalance the potential harmful effects.

In addition to the studies cited above, recent studies have shown that patients on anticoagulation tend to have smaller vegetations and fewer cerebrovascular complications.^11–13 Snygg-Martin et al¹¹ and Rasmussen et al¹² found not only that cerebrovascular complications were less common in patients already on anticoagulation at the time infectious endocarditis was diagnosed, but also that no increase in the rate of hemorrhagic lesions was reported.

These were all nonrandomized studies, and most of the patients in them had native valve infectious endocarditis diagnosed at an early stage. Importantly, these studies found that the beneficial effects of anticoagulation were only present if the patient was receiving warfarin before infectious endocarditis was diagnosed and antibiotic therapy was initiated. No benefits from anticoagulation were demonstrated once antimicrobial therapy was begun.

Similarly, Anavekar et al¹⁴ showed that embolic events occurred significantly less often in those who were currently on continuous daily antiplatelet therapy, suggesting that receiving antiplatelet agents at baseline protects against cardioembolic events in patients who develop infective endocarditis. However, the only randomized trial examining the initiation of antiplatelet therapy in patients diagnosed with infectious endocarditis receiving antibiotic treatment showed that adding aspirin did not reduce the risk of embolic events and was associated with a trend toward increased risk of bleeding.¹⁵

A recent large cohort study suggested that infectious endocarditis patients who receive anticoagulation therapy may have a higher incidence of cerebrovascular complications (hazard ratio 1.31, 95% confidence interval 1.00–1.72, P = .048), with a particular association of anticoagulation therapy with intracranial bleeding (hazard ratio 2.71, 95% confidence interval 1.54–4.76, P = .001).¹⁶

Another provocative link supported by the same study was a higher incidence of hemorrhagic complications with anticoagulation in patients with infectious endocarditis caused by Staphylococcus aureus, an association also suggested by older data from Tornos et al,⁸ but not seen in a study by Rasmussen et al.¹²

Continuing anticoagulation is an individualized decision

The benefit or harm of anticoagulation in patients with infectious endocarditis may be determined at least in part by a complex mix of factors including the valve involved (embolic events are more common with mitral valve vegetations than with aortic valve vegetations), vegetation size (higher risk if > 1 cm), mobility of vegetations, and perhaps the virulence of the causative organism.^16,17 The fact that antimicrobial therapy obviates any beneficial effect of anticoagulation speaks strongly against starting anticoagulation therapy in infectious endocarditis patients with the sole purpose of reducing stroke risk.

Without large randomized trials to better delineate the risks and benefits of continuing preexisting anticoagulation in all patients with infectious endocarditis, patients already receiving anticoagulants need a careful, individualized risk-benefit assessment. Current guidelines agree that newly diagnosed infectious endocarditis per se is not an indication for anticoagulation or aspirin therapy (Table 1).^1–3