Optimal antiplatelet and anticoagulant therapy in patients with oral anticoagulation in coronary stenting

Chronic oral anticoagulation (OAC) is necessary in patients with mechanical heart valves and in most patients with atrial fibrillation (AF). A large subgroup of these patients has concomitant coronary artery disease (CAD). When these patients have to undergo percutaneous coronary intervention (PCI), additional dual antiplatelet treatment (DAPT) with aspirin and a P2Y12 inhibitor becomes indicated to prevent stent thrombosis. In a rapidly ageing community, the number of patients suffering both AF and CAD is steadily increasing. Up to 2012 these patients were treated with the so-called triple therapy that is the combination of aspirin, clopidogrel and a vitamin K antagonist (VKA). However, this triple therapy also has its downsides. There is an association with an annual bleeding risk of up to 45% and bleeding is the Achilles-heel of triple therapy because it is the associated with an increased mortality risk. This thesis is based upon the clinical problem in this high-risk patient group (AF & PCI) that we encountered in 2007-2008 when patients had a high bleeding tendency when treated with triple therapy. We set out to decrease the bleeding risk without increasing the risk of stent thrombosis. Although triple therapy is still recommend by the guidelines, these recommendations are based on expert opinion and not on randomised trials. In this thesis we provide evidence that suggests that the increased bleeding risk outweighs the efficacy (preventing stent thrombosis, myocardial infarction (MI), stroke and thromboembolism) benefit of triple therapy in these patients and we present a possible new strategy of VKA and a P2Y12 inhibitor alone. The results of this randomised WOEST trial were presented in the hot line session of the 2012 annual meeting of the European Society of Cardiology in Munich and published in the Lancet. Second, we focus on the possible pitfall of VKA as it may modify the clopidogrel drug responsiveness and efficacy. However, the clinical impact of this finding on the risk of atherothrombotic events in patients on long term OAC undergoing PCI is unclear. Further investigation on this topic is needed. Third, the optimal peri-procedural PCI strategy in patients on OAC is highlighted. In a sub-analysis of the WOEST study, uninterrupted oral anticoagulation was not associated with an increase of bleeding or MACCE compared to bridging therapy. This study supports the current guidelines to adopt a peri-procedural uninterrupted oral anticoagulation strategy in patients on long term OAC who undergo PCI. Finally, we focus on stent choice in patients on OAC who undergo PCI. For patients on OAC who need to undergo PCI, guidelines (based on expert opinion) recommend the use of bare metal stents (BMS) but a sub-analysis of the WOEST trial showed that in patients treated with OAC who undergo PCI the implantation of DES was not associated with an increase of bleeding or ischemic events compared to BMS. The use of DES was associated with a significantly lower rate of TVR and therefore the use of DES seems a reasonable option in patients on long term OAC who undergo PCI.