Immunosuppressive drugs, such as corticosteroids and rituximab, are neither thought to be necessary in the acute phase of VTE in APS nor effective in preventing recurrent VTE associated with aPLs, except for resistant APS [14–16], and in the case of catastrophic APS. Combined VKA and acetylsalicylic acid (ASA) have been proposed in patients with APS and arterial events [17]. However, since the evidence of an increased efficacy of this association is lacking and the increased risk of bleeding is proven, a careful assessment of the patients’ bleeding risk should be performed before starting this regimen. Statins, hydroxychloroquine, or LMWH has also been suggested in patients with recurrent thrombosis during VKA, provided that any possible attempt to optimize the quality of VKA treatment, in order to obtain a good time in therapeutic range, has been made (Table 15.2).

The limitation and, in some cases, the difficulty to correctly manage VKA therapy have driven the search for new oral anticoagulant drugs (NOA). To date, three NOA have been licensed by FDA and EMA for the prevention of VTE in patients undergoing major elective orthopedic surgery and of stroke and systemic embolism in patients with atrial fibrillation: the direct inhibitor of coagulation factor IIa dabigatran etexilate and the direct inhibitors of factor Xa rivaroxaban and apixaban [18]. Other NOA are currently under investigation (edoxaban, betrixaban, others) and will probably be available in a few years. Rivaroxaban has already been licensed also for patients with VTE, both for the acute treatment and for the secondary prophylaxis. These agents represent a major advance as, unlike VKA, they do not interact with diet and alcohol intake and have few reported drug interactions affecting anticoagulant intensity. Furthermore, laboratory monitoring is not routinely required due to their predictable anticoagulant effects. Table 15.3 summarizes the main pharmacological characteristics of NOA already available in Europe for clinical use.

The efficacy and safety of NOA in the prevention of stroke or systemic embolization in patients with non-valvular atrial fibrillation have been demonstrated in large phase III clinical trials, all showing that these drugs are as effective as warfarin, with a similar incidence of major bleeding [19–21]. Of particular relevance is the lower incidence of intracranial hemorrhage in patients taking NOA than in those taking VKA. Conversely, the rate of GI bleeding is higher in the former group than in the latter.