The good, the bad, and the ugly: triple therapy after PCI in patients requiring chronic anticoagulation.

A percutaneous coronary intervention presents unique challenges to the antithrombotic management of patients requiring chronic anticoagulation. Warfarin is often discontinued several days before a percutaneous intervention, exposing patients to the risk of potentially life-threatening thrombo-embolic complications. In contrast, bridging the period after the intervention until a therapeutic INR is reached again often requires additional anticoagulation with heparin, greatly increasing the risk of in-hospital bleeding complications. One solution to this problem is to consider a transradial approach, which not only obviates the need for temporarily discontinuation of anticoagulation therapy, but also avoids having to administer additional heparin while restarting warfarin in patients already receiving dual antiplatelet therapy. Finding the ideal chronic antithrombotic combination after hospital discharge appears to be an even more challenging problem. Triple therapy, i.e. dual antiplatelet therapy and warfarin, appears to be the ideal approach after PCI in patients requiring chronic anticoagulation: aspirin plus clopidogrel avoids stent thrombosis, whereas warfarin prevents thrombo-embolism. Unfortunately, this combination clearly increases the risk of bleeding complications during follow-up after stenting. To date, it remains unclear whether we have good alternative antithrombotic strategies for this growing patient population to a large extent because of the absence of the study data. All boils down to finding a perfect balance between risk of stent thrombosis and thrombo-embolic complications and the risk of major bleeding. Unfortunately, the present study by Karjalainen et al. indicates that this balance is very delicate and requires treading a very thin line dictated by careful weighing of all risk factors in each individual patient. Before the advent of thienopyridines, aspirin plus oral anticoagulation was the standard antithrombotic regimen after stenting. This combination is still often used after stenting in patients requiring chronic anticoagulation. A recent meta-analysis, nevertheless, indicates that the combination of warfarin and aspirin after PCI is associated not only with a higher risk of stent thrombosis or myocardial infarction, but also with a higher incidence of serious bleeding complications. Can aspirin plus clopidogrel then be considered as an alternative regimen? Dual antiplatelet therapy is undoubtedly current evidence-based practice for the prevention of in-stent thrombosis, but does not adequately protect against thrombo-embolic complications. Nevertheless, not all patients requiring chronic anticoagulation have a similar risk of thrombo-embolic complications. Patients with a recent venous thrombo-embolic event or with mechanical prosthetic heart valves, especially tilting-disc aortic valves and valves in the mitral position, are at very high risk for thrombo-embolism. In contrast, the thrombo-embolic risk is probably somewhat less in most patients with atrial fibrillation or dilated left ventricle or an aortic prosthetic valve, depending on age and co-morbidities. Consequently, it appears to be reasonable to adjust the need or extent of anticoagulation to the perceived thrombo-embolic risk in patients after coronary stenting. More frequent lab analyses might also be helpful to ensure international normalized ratio (INR) values well within recommended evidence-based ranges. Likewise, chronic aspirin doses should also be kept within the 75– 100 mg range as recommended by the ESC guidelines. To date, only a handful of small retrospective studies have addressed the safety of triple therapy. Unsurprisingly, most find an increased bleeding risk. One study in elderly patients undergoing PCI found a 1.9 times higher risk of bleeding with triple therapy (95% CI 1.3–2.9). Another study assessing triple therapy after primary PCI for ST-elevation myocardial infarction even reported an unacceptably high transfusion rate of 21% at 1-year follow-up. However, major bleeding complications remain a serious concern. Even nuisance bleedings during long-term follow-up can result in a catastrophe, because patients or their physician might be tempted to stop aspirin, clopidogrel, or the anticoagulant. Permanent discontinuation of either aspirin or clopidogrel after a short and usually innocent episode of bleeding will undeniably increase the risk of stent thrombosis. Karjalainen et al. report their retrospective study on antithrombotic strategies after coronary stenting in 239 patients requiring long-term oral anticoagulation, the largest study on triple therapy to date. Atrial fibrillation The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology