Apixaban in renal insufficiency: successful navigation between the Scylla and Charybdis

Anticoagulation for stroke prevention in atrial fibrillation has traditionally been performed by vitamin K antagonists. Although effective under optimal conditions, the imminent risk of severe haemorrhage is a major cause for substantial underutilization of these drugs, even in patients at high risk of thrombo-embolic events. The recent introduction of the direct thrombin inhibitor dabigatran, as well as the oral factor Xa inhibitors rivaroxaban and apixaban ( Figure 1 ) has resulted in a paradigm shift regarding the treatment of these patients. While large-scale clinical trials including Re-LY, ROCKET-AF, and ARISTOTLE have (essentially) all indicated superiority of the respective substance compared with warfarin in stroke prevention, these agents were equally shown to be superior with respect to bleeding events, especially major, life-threatening, and intracranial haemorrhage.1–3 The initial enthusiasm associated with these novel agents was, however, dampened shortly after their introduction when reports of major haemorrhages surfaced, indicating that an unrestricted and injudicious use may put certain patients at an elevated risk for adverse events. Indeed, it quickly became clear that especially dabigatran, which is 80% renally cleared, has a significant potential for severe bleeding in patients with reduced renal function. Figure 1. Point of action of novel oral anticoagulants in the coagulation cascade. See text for details. VKA, vitamin K antagonist. Adapted from Steffel and Braunwald.Patients with renal insufficiency, however, are problematic for any kind of anticoagulant treatment due to the increased risk for both thrombo-embolic and bleeding events in this situation.4 A recent cohort study once more identified reduced renal function as an independent predictor of cerebral ischaemic events, with a continuous increase in risk with decreasing kidney function.5 This is even further potentiated in patients with end-stage renal disease as well as those on dialysis. In …