Dual therapy was found to be more effective in reducing the risk for bleeding in patients with atrial fibrillation who have undergone percutaneous coronary intervention, but may be associated with increased risk for ischemic events compared with triple therapy, according to the results of a systemic review and meta-analysis published in Annals of Internal Medicine.1

Atrial fibrillation is thought to occur in 5% to 10% of patients who have undergone percutaneous coronary intervention. In this patient group, choosing the most efficacious antithrombotic therapy may reveal difficult. Investigators aimed to determine whether dual or triple therapy is more appropriate for the management of atrial fibrillation in patients with coronary artery disease who had percutaneous coronary intervention. Dual therapy consists in a direct oral anticoagulants plus a P2Y12 inhibitor, and triple therapy, in a P2Y12 inhibitor, in combination with aspirin and a vitamin K antagonist.

The researchers performed a literature search of the PubMed, EMBASE, and Cochrane Library databases and of the ClinicalTrials.gov website from inception through December 2019. Websites for major cardiovascular and medical journals, as well as references of individual studies, were manually searched for additional relevant studies. Randomized clinical trials in which dual and triple therapy were compared in this patient population were included for analysis.


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Of the 265 articles identified in the literature search, 4 randomized clinical trials were selected for analysis (n=7953). The mean age ranged from 68.6 to 71.7 years and the percentage of women enrolled was between 23.6% and 30.7%. The median follow-up duration was 1 year (interquartile range, 0.87-1.04 years).

Dual vs triple therapy was associated with a lower risk for major bleeding (risk difference [RD], -0.013; 95% CI, -0.025 to -0.002). The effect of dual vs triple therapy on the risks for all-cause mortality (RD, 0.004; 95% CI, -0.010 to 0.017), cardiovascular mortality (RD, 0.001; 95% CI, -0.011 to 0.013), myocardial infarction (RD, 0.003; 95% CI, -0.010 to 0.017), and stent thrombosis (RD, 0.003; 95% CI, -0.005 to 0.010) were found to be inconclusive, based on low-certainty evidence. However, the upper limits of the confidence intervals were compatible with a potential increased risk for those outcomes in patients who received dual vs triple therapy.

The risks for intracerebral hemorrhage (RD, -0.004; 95% CI, -0.009 to 0.000) and stroke (RD, -0.003; 95% CI, -0.010 to 0.005) were comparable between dual and triple therapy.

Study limitations include the heterogeneity of study designs, particularly with regard to anticoagulant dosage and types of P2Y12 inhibitors used.

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“In adults with [atrial fibrillation] after [percutaneous coronary intervention], dual therapy reduces risk for bleeding compared with triple therapy, whereas its effects on risks for death and ischemic end points are still unclear,” the study authors concluded.1

In an accompanying editorial, John U. Doherty, MD, professor of cardiology and physician at Jefferson Heart Institute in Philadelphia, Pennsylvania commented on the clinical implications of these results with regard to balancing bleeding and thrombosis risk. “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 antiplatelet therapy].”2

Dr Doherty noted that, while the answer remains unclear, the field is rapidly evolving. “Lesion complexity, patient-specific bleeding risk, and whether stenting is elective or emergent are factors to weigh in determining the duration and intensity of combined anticoagulant and antiplatelet therapy. Navigating the competing risks remains a challenge. Stent technology is maturing, and which P2Y12 inhibitor to prescribe remains a question, especially when treatment with clopidogrel is unsuccessful. Stay tuned, because practice will surely continue to evolve.”2

References

  1. Khan SU, Osman M, Khan MU, et al. Dual versus triple therapy for atrial fibrillation after percutaneous coronary intervention: A systematic review and meta-analysis [published online March 17, 2020]. Ann Intern Med. doi:10.7326/M19-3763
  2. Doherty JU. Combined antiplatelet and anticoagulant therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention: Navigating between scylla and charybdis [published online March 17, 2020]. Ann Intern Med. doi:10.7326/M20-0572