In patients with atrial fibrillation who have experienced MI or undergone percutaneous coronary intervention (PCI), treatment with a combination of direct oral anticoagulants (DOACs) and dual antiplatelet therapy (DAPT) could significantly decrease the risk of bleeding and other major thromboembolic events, according to research published ahead of print in the Journal of the American College of Cardiology.
The study, authored by Caroline Sindet-Pederson, MSc, and colleagues in the Department of Cardiology at Copenhagen University Hospital Herlev and Gentofte in Hellerup, Denmark, found the mix of DOACs and DAPT to be more protective than vitamin K antagonists (VKAs), which are commonly prescribed to AFib patients at an increased risk for stroke.
Those patients are typically recommended for lifelong anticoagulation therapy with either VKAs or DOACs like rivaroxaban, apixaban and edoxaban, Sindet-Pederson and co-authors wrote, but treatment is more complex if patients present with multiple cardiovascular complications.
“AF patients experiencing an MI or undergoing a PCI are concomitantly treated with an antiplatelet, such as aspirin, clopidogrel or both, because of an increased risk of coronary vascular events,” they said. “Dual or triple antithrombotic therapy may be effective in reducing the risk of thromboembolic events, but the risk of bleeding inherent to treatment has been shown to increase with combinations of antiplatelets and oral anticoagulants.”
The researchers drew from Danish nationwide registries to identify AFib patients who’d been admitted to hospitals in Denmark for MI or PCI between August 2011 and June 2017 and were treated with a combination of oral anticoagulants and antiplatelet therapy. The 3,222 individuals included in the study population were assigned to one of four treatment regimens: VKA with single antiplatelet therapy (SAPT), DOAC and SAPT, VKA and DAPT or DOAC and DAPT.
Patients were followed up with for 12 months or until an outcome was reached, but at the three-month mark Sindet-Pederson et al. said there was already a “significant difference” in the absolute risk of MI associated with DOAC and SAPT compared to VKA and SAPT. The absolute risk reduction of 1.53 percent suggested DOACs were a more effective treatment path—something that was echoed in the DAPT cohorts.
Compared with VKA and DAPT, DOAC and DAPT was associated with a decreased risk of bleeding at three months, with no significant difference in the absolute risk of all-cause mortality, stroke or MI in the population. The absolute risk difference in bleeding between the groups was 1.96 percent.
“Our data suggest that despite lack of trial evidence on the safety and effectiveness of DOAC versus VKA in combination with antiplatelets, DOACs seem safe and effective in real-world AFib patients following MI or PCI,” Sindet-Pederson and colleagues wrote.
Still, C. Michael Gibson, MS, MD, of Beth Israel Deaconess Medical Center in Boston, Massachusetts, said in a related editorial those conclusions should be interpreted with caution.
The study ignored something crucial, he and two co-authors said. A censoring period of seven days after hospital discharge means the Danish analysis didn’t capture in-hospital or early bleeding events during the highest-risk period after PCI.
The bleeding rate was also much lower in the DOAC and DAPT group than the DOAC and SAPT cohort—something Gibson and colleagues called “biologically implausible” if the two patient groups were similar. They suggested the inconsistency might be attributed to unidentified confounders.
“Although Sindet-Pederson et al. were able to confirm the increased bleeding risk associated with VKA-based triple therapy, a conclusion supported by prior registries and two randomized controlled trials, the analyses among DOAC and VKA-based dual therapies, which lack external validation from randomized controlled trials, should be interpreted with caution,” they said. “These limitations re-enforce the need for randomized data from large-scale national/international registries with unselected patients to combine the strengths of randomized trials with the generalizability of registries.”
After graduating from Indiana University-Bloomington with a bachelor’s in journalism, Anicka joined TriMed’s Chicago team in 2017 covering cardiology. Close to her heart is long-form journalism, Pilot G-2 pens, dark chocolate and her dog Harper Lee.