What is the best approach to antithrombotic therapy for patients with atrial fibrillation after undergoing percutaneous coronary intervention?

Among patients with atrial fibrillation who had undergone percutaneous coronary intervention, dual therapy with dabigatran and clopidogrel caused fewer major bleeding events than triple therapy with warfarin, aspirin, and clopidogrel. Either dose of dual therapy with dabigatran was superior to warfarin triple therapy with respect to bleeding events, and was noninferior with respect to thromboembolic prevention. The higher dose may be more appropriate for patients at high risk of thromboembolism, and the lower dose for those at higher risk of bleeding. (LOE = 1b)

Cannon CP, Bhatt DL, Oldgren J, et al, for the RE-DUAL PCI Steering Committee and Investigators. Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N Engl J Med 2017;377(16):1513-1524.  [PMID:28844193]

Randomized controlled trial (double-blinded)

Industry

Concealed

Outpatient (any)

These researchers recruited adults with nonvalvular atrial fibrillation who had undergone PCI including stent placement within the previous 5 days. The 2725 participants were randomized receive to 1 of 3 antithrombotic strategies: (1) dabigatran 110 mg twice daily plus clopidogrel 75 mg daily, (2) dabigatran 150 mg twice daily plus clopidogrel, or (3) triple therapy with warfarin to an international normalized ratio of 2 to 3 plus low-dose aspirin plus clopidogrel. Approximately 10% of patients received ticagrelor instead of clopidogrel. Participants had a mean age of 70 years. Randomization was stratified by age and location; dabigatran is not approved in the 150-mg dose for patients older than 80 years in some countries, so there were fewer patients in that treatment group than in the other 2 groups. This was a noninferiority trial for the comparison of the 2 dual therapy dabigatran groups with the current guideline-recommended triple therapy. Groups were balanced at the start of the trial (other than by age, as noted above) and analysis was by intention to treat. Between 0.5% and 4% of patients in each group were lost to follow-up or withdrew consent, and 13.0% to 16.6% stopped taking the study drugs during the trial period. Patients were treated for a mean of 12 months, and followed up for a total of 14 months. Major bleeding was less common in both of the dabigatran dual therapy groups than in the triple therapy group (5.0% vs 9.0% for the 110-mg dose; P < .001; number needed to treat [NNT] = 25, and 5.6% vs 9.0% for the 150-mg dose; P = .02; NNT = 29). Regarding the combined outcome of myocardial infarction, stroke, systemic embolism, death, or unplanned revascularization, the authors report that both of the dabigatran regimens were noninferior to triple therapy with warfarin. Although statistically "noninferior," the likelihood of this combined efficacy outcome was 11.8% in the 150-mg dabigatran group, 13.4% in the triple therapy group, and 15.2% in the 110-mg dabigatran group.