TOPLINE

A meta-analysis of five randomised controlled trials (RCTs) found that oral anticoagulation (OAC) monotherapy was associated with a significantly lower risk for net adverse clinical events (NACEs) and major bleeding than combination therapy comprising OAC plus a single antiplatelet therapy among patients with stable chronic coronary syndrome (CCS) who required long-term OAC; however, the risk for major adverse cardiovascular events (MACEs) and ischaemic outcomes did not differ significantly between the two strategies.

METHODOLOGY

• Researchers conducted a systematic review and meta-analysis of RCTs identified through searches of multiple databases up to February 2026 to compare OAC monotherapy with combination therapy (OAC plus single antiplatelet therapy) in patients with stable CCS who required long-term OAC.
• A total of five RCTs involving 5777 patients with stable CCS were included in the meta-analysis. The median follow-up duration ranged from 12 to 30 months across trials.
• CCS was defined according to each trial's prespecified inclusion criteria such as a history of percutaneous coronary intervention and/or coronary artery bypass grafting or angiographically documented coronary artery disease that did not require revascularisation.
• Across the included RCTs, OAC regimens comprised apixaban, dabigatran, edoxaban, rivaroxaban, and vitamin K antagonists. For combination therapy, OAC was most frequently paired with aspirin, followed by P2Y12 inhibitors, with only limited use of beraprost and sarpogrelate.
• The primary outcome was a NACE, a composite of ischaemic and bleeding events; key secondary outcomes included MACEs, major bleeding, and the composite endpoint of major or clinically relevant non-major bleeding.

TAKEAWAY

• Across all RCTs, OAC monotherapy was associated with a 39% lower risk for NACEs than combination therapy (hazard ratio [HR], 0.61; 95% credible interval [CrI], 0.43-0.85).
• Across all RCTs, OAC monotherapy was associated with a 53% lower risk for major bleeding than combination therapy (HR, 0.47; 95% CrI, 0.30-0.71). In four RCTs, OAC was also associated with a 53% lower risk for major or clinically relevant non-major bleeding (HR, 0.47; 95% CrI, 0.31-0.66).
• The risk for MACEs and cardiovascular and all-cause deaths did not differ significantly between OAC monotherapy and combination therapy across all RCTs. No significant difference was observed for myocardial infarction and ischaemic stroke across four RCTs each and unplanned revascularisation across three RCTs.
• In subgroup analyses, OAC monotherapy was associated with more favourable MACE outcomes among patients receiving direct OACs than among those receiving vitamin K antagonists (P for interaction = .02).

IN PRACTICE

"In stable CCS patients with concomitant indication for long-term OAC, OAC monotherapy significantly reduces bleeding events compared to combination therapy without evidence for a concomitant increase in ischemic risk. These findings provide supportive evidence for the current ESC [European Society of Cardiology] guideline recommendations and reinforce the current standard of care in this population," the researchers of the study wrote.

SOURCE

The study was led by Anastasios Tsarouchas, Cardiology and Intensive Care Medicine, Landesklinikum Mistelbach-Gänserndorf, Mistelbach, Austria. It was published online on August 11, 2026, in the European Journal of Preventive Cardiology.

LIMITATIONS

Variations in NACE and MACE definitions across trials may have introduced heterogeneity in the pooled analyses. Differences in the types and doses of anticoagulants used across trials may have contributed to variability in the findings. Follow-up was extended to a maximum of 30 months, limiting the assessment of longer-term outcomes.

DISCLOSURES

The study did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors declared having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.