New oral anticoagulants in addition to single or dual antiplatelet therapy after an acute coronary syndrome: a systematic review and meta-analysis

Abstract

BackgroundOral anticoagulation in addition to antiplatelet treatment after an acute coronary syndrome might reduce ischaemic events but increase bleeding risk. We performed a meta-analysis to evaluate the efficacy and safety of adding direct thrombin or factor-Xa inhibition by any of the novel oral anticoagulants (apixaban, dabigatran, darexaban, rivaroxaban, and ximelagatran) to single (aspirin) or dual (aspirin and clopidogrel) antiplatelet therapy in this setting.Methods and resultsAll seven published randomized, placebo-controlled phase II and III studies of novel oral anticoagulants in acute coronary syndromes were included. The database consisted of 30 866 patients, 4135 (13.4%) on single, and 26 731 (86.6%) on dual antiplatelet therapy, with a non-ST- or ST-elevation acute coronary syndrome within the last 7–14 days. We defined major adverse cardiovascular events (MACEs) as the composite of all-cause mortality, myocardial infarction, or stroke; and clinically significant bleeding as the composite of major and non-major bleeding requiring medical attention according to the study definitions. When compared with aspirin alone the combination of an oral anticoagulant and aspirin reduced the incidence of MACE [hazard ratio (HR) and 95% confidence interval 0.70; 0.59–0.84], but increased clinically significant bleeding (HR: 1.79; 1.54–2.09). Compared with dual antiplatelet therapy with aspirin and clopidogrel, adding an oral anticoagulant decreased the incidence of MACE modestly (HR: 0.87; 0.80–0.95), but more than doubled the bleeding (HR: 2.34; 2.06–2.66). Heterogeneity between studies was low, and results were similar when restricting the analysis to phase III studies.ConclusionIn patients with a recent acute coronary syndrome, the addition of a new oral anticoagulant to antiplatelet therapy results in a modest reduction in cardiovascular events but a substantial increase in bleeding, most pronounced when new oral anticoagulants are combined with dual antiplatelet therapy.

2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS

“…516 Co-prescription of OAC with antiplatelet therapy, in particular triple therapy, increases the absolute risk of major haemorrhage. 445 519 The addition of a NOAC increased the bleeding risk by 79-134%, while reducing recurrent ischaemic events only marginally in patients without AF. OAC monotherapy, and not combination therapy with antiplatelets, is recommended in AF patients with stable CAD but without an ACS and/or coronary intervention in the previous 12 months.…”

Therapeutic strategies for atherosclerosis and atherothrombosis: Past, present and future

“…Two direct thrombin inhibitors, dabigatran and ximelagatran, have been tested. Dabigatran only afforded minor effects on cardiovascular events but significantly increased the risk of bleeding (62). Ximelagatran showed an additional reduction in cardiovascular events on top of aspirin, but was withdrawn from the market due to liver toxicity (63).…”

Prosthodontics: Tenacious lump of calculus

“…1 Clinical trials elucidated a dose-dependent increase in major bleeding events, including internal (eg intracranial), with apixaban and rivaroxaban when combined with dual antiplatelet therapy. 2 Since August 2015 recommendations by the Scottish Dental Clinical Effectiveness Programme (SDCEP) in relation to combined antiplatelet and NOACs dual therapy do not advise a specific course of action and they only indicate a need for consultation with a general medical practitioner or specialist. 3 Consultation with an anticoagulation clinic or clinical haematologist is always necessary prior to dental surgery for patients in combined dual anticoagulant therapy due to considerably higher risk of bleeding.…”

“…1 Adverse drug reactions (ADRs) to cardiovascular medication were outlined recently in the literature. 2,3 The prevalence of oral manifestations of ADRs is not fully known, and the pathophysiological mechanisms for which these occur have yet to be fully elucidated; there have been reports in the literature associating oral ADRs to simvastatin use.…”