Dual, not Triple Therapy Reduces Bleeding Events in AF Patients After PCI

Safi Khan, MD

Results of a new study are offering clinicians guidance on choosing between dual and triple therapy for adults with atrial fibrillation (AF) after percutaneous coronary intervention (PCI).

The study, which was a meta-analysis of 4 trials including nearly 8k patients, revealed dual therapy with a DOAC plus P2Y12 inhibitor resulted in less bleeding than triple therapy with a vitamin K antagonist plus aspirin and a P2Y12 inhibitor in adults with nonvalvular AF after PCI, but the impact on the risk of death and ischemic endpoints remains unclear.

With patients with ischemic heart disease and AF undergoing PCI presenting a unique treatment challenge, investigators from Johns Hopkins University and West Virginia University sought to compare the 2 approaches and its impact on bleeding, mortality, and ischemic outcomes. To do so, they conducted an analysis of trials examining the issue in multiple databases, including PubMed, EMBASE, and the Cochrane Library and ClinicalTrials.gov.

For inclusion in the analysis, studies had to be randomized controlled trials, report all of the aforementioned outcomes, and 50% or more of the participants needed to have received PCI. Trials were excluded if they were observation studies, registries, or post hoc analyses of randomized clinical trials. In total, 265 articles were screen for eligibility and 4 randomized clinical trials met inclusion criteria.

The 4 trials included, which were PIONEER AF-PCI, RE-DUAL PCI, AUGUSTUS, and ENTRUST-AF PCI, encompassed a total of 7953 patients. All 4 of the trials included were open-label and each included more than 1500 patients. DOACs examined include apixaban, rivaroxaban, dabigatran, and edoxaban.

Over a median follow-up period of 1 year, high-certainty evidence indicated dual therapy 3 was associated with lower risks for TIMI major bleeding (Risk Difference (RD) 0.013; 95% CI, 0.025-0.002), TIMI major and minor bleeding (RD 0.031; 0.049-0.012), and trial defined bleeding (RD 0.072; CI, 0.129-0.015) compared to those receiving triple therapy.

Additionally, low-certainty evidence showed dual therapy had an inconclusive effect on risks for all-cause mortality (RD 0.004; CI, 0.010-0.017), cardiovascular mortality (RD 0.001; CI, 0.011 to 0.013), myocardial infarction (RD 0.003; CI, 0.010-0.017), stent thrombosis (RD 0.003; CI, 0.005-0.010), and MACE compared to triple therapy. Investigators pointed out there were no statistically significant differences between the therapies in terms of intracerebral hemorrhage (RD 0.004; CI, 0.009-0.000).

In a related editorial, John Doherty, MD, of Jefferson Heart Institute in Philadelphia commended the study’s investigators and results for offering guidance on what can sometimes present a serious challenge for cardiologists.

“Are these separate meta-analyses compatible, and did Khan and colleagues get it right? I believe that the answer to both questions is yes. Because bleeding events are much more frequent than thrombotic events, even after pooling data from 4 trials, it is difficult to know definitively whether and to what extent thrombotic events are increased with (dual antithrombotic therapy),” Doherty wrote.

This study, “Dual Versus Triple Therapy for Atrial Fibrillation After Percutaneous Coronary Intervention,” was published in the Annals of Internal Medicine.