Optimal anticoagulation regimen in AF and CAD 1-year post-PCI undetermined
The efficacy of oral anticoagulation (OAC) alone without antiplatelet therapy in patients with atrial fibrillation (AF) and coronary artery disease (CAD) who have undergone percutaneous coronary intervention (PCI) remains to be seen, with findings of the OAC-ALONE* trial proving inconclusive, according to a study presented at the recent TCT 2018 symposium.
“This randomized trial did not establish noninferiority of OAC alone to combined OAC and antiplatelet therapy in patients with AF and stable CAD beyond 1 year after stenting,” said the authors.
Participants in this prospective, multicentre, open-label, noninferiority trial were 696 patients with AF and stable CAD (mean age 75 years, 85.2 percent male, mean CHA2DS2-VASc score 4.6) who had undergone PCI with stents. They were randomized to receive either OAC alone (warfarin or direct OACs) or in addition to single antiplatelet therapy (aspirin or clopidogrel) and were followed up for a median 2.5 years. Warfarin was the OAC used in most patients (75.2 percent).
The primary outcome – a composite of all-cause mortality, myocardial infarction (MI), stroke, or systemic embolism – occurred in 15.7 and 13.6 percent of patients on OAC alone and OAC plus antiplatelet therapy, respectively, with OAC alone not meeting noninferiority criteria to OAC plus antiplatelet therapy (hazard ratio [HR], 1.16, 95 percent confidence interval [CI], 0.79–1.72; p=0.20 for noninferiority and p=0.45 for superiority). [TCT 2018, Late-Breaking Trials 4; Circulation 2018;doi:10.1161/CIRCULATIONAHA.118.036768]
When incidence of major bleeding was added to the composite, OAC alone was noninferior to OAC plus antiplatelet therapy (19.5 percent vs 19.4 percent, HR, 0.99, 95 percent CI, 0.71–1.39; p=0.016 for noninferiority and p=0.96 for superiority).
With regard to a composite of cardiovascular death, MI, ischaemic stroke, systemic embolism, and major bleeding, OAC alone demonstrated noninferiority to OAC plus antiplatelet therapy (16.0 percent vs 17.1 percent, HR, 0.92; p=0.009 for noninferiority and p=0.66 for superiority).
MI occurred in 2.3 and 1.2 percent of patients on OAC alone and OAC plus antiplatelets, respectively, stroke or systolic embolism in 3.8 and 5.5 percent, respectively, and major bleeding in 7.8 and 10.4 percent, respectively. Incidence of stent thrombosis was low (two patients on OAC alone).
“In patients with concomitant AF and stable CAD beyond 1 year after coronary stent implantation, the European Society of Cardiology guidelines have consistently recommended OAC without antiplatelet therapy,” said study author Dr Yukiko Nakano from the Kyoto University Graduate School of Medicine in Kyoto, Japan.
“However, in routine clinical practice, antiplatelet agents are still commonly used in combination with OAC beyond 1 year after coronary stenting, mainly due to concern related to risk of stent thrombosis after cessation of antiplatelet therapy,” said Nakano and co-authors.
“[As] there were numerically fewer MI and stent thromboses in the combined OAC and antiplatelet therapy group … continuation of single antiplatelet on top of OAC beyond 1 year after stenting might be preferable for AF patients with high thrombotic and low bleeding risk,” said the authors. “[H]owever, AF patients post-stenting are often elderly and thus, are at high risk of bleeding,” they said.
The primary endpoint results could have been due to early termination of patient enrolment leading to the study being underpowered to determine the outcomes, said the authors, highlighting that a major impedance to recruitment was reluctance among cardiologists to discontinue antiplatelet therapy for fear of stent thrombosis.
Larger randomized trials with adequate power are needed to “determine the optimal antithrombotic regimen in this population”, they said.