Practice Update: Cardiology

AHA 2016 31

Full-dose oral triple therapy with DAPT and full-dose anticoagulation should be avoided in patients with atrial fibrillation Results of PIONEER to date lead to the conclusion that abandoning full-dose triple therapy is warranted in patients with atrial fibrillation. This conclusion was explained in a discussion of PIONEER at AHA 2016. D eepak L. Bhatt, MD, MPH, of Brigham and Women’s Hospital, Boston, Massachusetts, explained that one of the most common conundrums in all of cardiovascular medicine

provide similar efficacy and reduced bleeding versus triple therapy (dual antiplatelet therapy plus full-dose vitamin K antagonism). Curiously, a signal of less ischaemic/thrombotic complications was suggested with double therapy, though these two trials were not powered for efficacy endpoints. It remained possible, however, that excess bleeding with triple therapy overwhelmed any potential gain in efficacy. Furthermore, the role, if any, of the novel oral anticoagulants in place of vitamin K antagonists such as warfarin remained poorly characterised. Interestingly, even when the duration of full dose triple therapy was 6 weeks in ISAR-TRIPLE, a large percentage of the bleeding had already occurred. Thus, abbreviating the course of full-dose triple therapy does not diminish the risks of bleeding as much as we would like to believe. If a patient passes this early potent bleeding stress test, the subsequent risk of bleeding is lower, but may still be substantial in terms of cumulative risk over time. These early and late bleeding risks seem to be particularly high in older patients. In the PIONEER Atrial Fibrillation – Percutaneous Coronary Intervention trial, 2124 stented patients with atrial fibrillation were randomised to one of three groups: • Group 1: reduced-dose rivaroxaban 15 mg daily plus a P2Y12 for 12 months. • Group 2: rivaroxaban 2.5 mg BID with stratification to a prespecified duration of dual antiplatelet therapy of 1, 6, or 12 months. • Group 3: the control arm of dose-adjusted vitamin K antagonism daily with a similar dual antiplatelet therapy stratification as above. The primary endpoint of the post hoc analysis, all-cause mortality or recurrent hospitalisation due to an adverse event, was significantly lower in both experimental arms than in the control arm: 34.9% in Group 1 and 31.9% in Group 2 vs 41.9% in Group 3. Mortality rates were similar in the three arms. The salutary effects seen in Group 1 and Group 2 were due to reductions in hospitalisations for both bleeding and cardiovascular causes, with no significant effect on other types of hospitalisations. No significant differences were observed between the two experimental arms. Some have speculated that in the patient in whom conventional full-dose triple therapy is contemplated, such as the patient with atrial fibrillation who harbours an acute coronary syndrome and/ or is undergoing a percutaneous coronary intervention, that left atrial appendage closure may provide the best option to address thromboembolic risk and bleeding simultaneously. Large randomised trials are necessary to compare these closure devices against novel oral anticoagulants. These include the novel dosing regimens studied in PIONEER.

pertains to the care of patients with atrial fibrillation who need percutaneous coronary intervention. Both dual antiplatelet therapy and oral anticoagulant therapy seem necessary to reduce risks of stent thrombosis and thromboembolism, respectively. Intensifying the antithrombotic regimen, however, leads to more bleeding. A greater appreciation of bleeding has emerged in recent years. Fatal or intracranial bleeding would provide a direct causal pathway for the now well-known association between bleeding and death. Bleeding may be associated with partial or complete interruption or cessation of the various components of the antithrombotic regimen. Other medications, such as statins and beta blockers, are sometimes also stopped and may or may not be resumed. Transfusions, either appropriately or inappropriately, may be administered. Hospitalisations frequently occur around major bleeding episodes, and these can lead to a series of tests and procedures, may increase the risk of nosocomial infections, or lead to other adverse sequelae from hospitalisation. Thus, through direct and indirect pathways, bleeding requiring hospitalisation can cause major morbidity, including cardiovascular morbidity. Another development concomitant with advances in our understanding

of anticoagulation and the introduction of novel oral anticoagulants into widespread clinical practice has been the evolution in stenting. Second-generation drug-eluting stents constitute a major advance. In addition to offering low restenosis rates, they appear to lead to lower stent thrombosis rates than first-generation drug-eluting stents or even older bare metal stents. This reduction in stent thrombosis is apparent in late and very late stent thrombosis, but also has been demonstrated with respect to early stent thrombosis, at least with certain second- generation drug-eluting stents. Two modest-size randomised trials, the What is the Optimal antiplatElet and anticoagulant therapy in patients with oral anticoagulation and coronary StenTing? (WOEST) and Triple Therapy in Patients on Oral Anticoagulation After Drug Eluting Stent Implantation (ISAR-TRIPLE), have shown that double therapy (single antiplatelet therapy plus full-dose vitamin K antagonists) appeared to

© AHA/Edmund D. Fountain 2016

DECEMBER 2016