Dual Versus Triple Therapy for Atrial Fibrillation After Percutaneous Coronary Intervention: A Systematic Review and Meta-analysis

Abstract

Background: The safety and effectiveness of dual therapy (direct oral anticoagulant [DOAC] plus P2Y12 inhibitor) versus triple therapy (vitamin K antagonist plus aspirin and P2Y12 inhibitor) in patients with nonvalvular atrial fibrillation (AF) after percutaneous coronary intervention (PCI) is unclear.

Purpose: To examine the effects of dual versus triple therapy on bleeding and ischemic outcomes in adults with AF after PCI.

Data sources: Searches of PubMed, EMBASE, and the Cochrane Library (inception to 31 December 2019) and ClinicalTrials.gov (7 January 2020) without language restrictions; journal Web sites; and reference lists.

Study selection: Randomized controlled trials that compared the effects of dual versus triple therapy on bleeding, mortality, and ischemic events in adults with AF after PCI.

Data extraction: Two independent investigators abstracted data, assessed the quality of evidence, and rated the certainty of evidence.

Data synthesis: Four trials encompassing 7953 patients were selected. At the median follow-up of 1 year, high-certainty evidence showed that dual therapy was associated with reduced risk for major bleeding compared with triple therapy (risk difference [RD], -0.013 [95% CI, -0.025 to -0.002]). Low-certainty evidence showed inconclusive effects of dual versus triple therapy on risks for all-cause mortality (RD, 0.004 [CI, -0.010 to 0.017]), cardiovascular mortality (RD, 0.001 [CI, -0.011 to 0.013]), myocardial infarction (RD, 0.003 [CI, -0.010 to 0.017]), stent thrombosis (RD, 0.003 [CI, -0.005 to 0.010]), and stroke (RD, -0.003 [CI, -0.010 to 0.005]). The upper bounds of the CIs for these effects were compatible with possible increased risks with dual therapy.

Limitation: Heterogeneity of study designs, dosages of DOACs, and types of P2Y12 inhibitors.

Conclusion: In adults with AF after PCI, dual therapy reduces risk for bleeding compared with triple therapy, whereas its effects on risks for death and ischemic end points are still unclear.

Primary funding source: None.

Figure 1.

Effect of dual versus triple therapy on TIMI major bleeding (top) and TIMI major and minor bleeding (bottom). AUGUSTUS = Open-Label, 2 × 2 Factorial, Randomized Controlled, Clinical Trial to Evaluate the Safety of Apixaban vs. Vitamin K Antagonist and Aspirin vs. Aspirin Placebo in Patients With Atrial Fibrillation and Acute Coronary Syndrome or Percutaneous Coronary Intervention; ENTRUST-AF PCI = Edoxaban Treatment Versus Vitamin K Antagonist in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention; GRADE = Grading of Recommendations Assessment, Development and Evaluation; PIONEER AF-PCI = Open-Label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention; RD = risk difference; RE-DUAL PCI = Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran vs. Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention; TIMI = Thrombolysis in Myocardial Infarction.

Figure 2.

Effect of dual versus triple therapy on all-cause mortality (top) and cardiovascular mortality (bottom). AUGUSTUS = Open-Label, 2 × 2 Factorial, Randomized Controlled, Clinical Trial to Evaluate the Safety of Apixaban vs. Vitamin K Antagonist and Aspirin vs. Aspirin Placebo in Patients With Atrial Fibrillation and Acute Coronary Syndrome or Percutaneous Coronary Intervention; ENTRUST-AF PCI = Edoxaban Treatment Versus Vitamin K Antagonist in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention; GRADE = Grading of Recommendations Assessment, Development and Evaluation; PIONEER AF-PCI = Open-Label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention; RD = risk difference; RE-DUAL PCI = Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran vs. Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.

Figure 3.

Effect of dual versus triple therapy on myocardial infarction (top) and stent thrombosis (bottom). AUGUSTUS = Open-Label, 2 × 2 Factorial, Randomized Controlled, Clinical Trial to Evaluate the Safety of Apixaban vs. Vitamin K Antagonist and Aspirin vs. Aspirin Placebo in Patients With Atrial Fibrillation and Acute Coronary Syndrome or Percutaneous Coronary Intervention; ENTRUST-AF PCI = Edoxaban Treatment Versus Vitamin K Antagonist in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention; GRADE = Grading of Recommendations Assessment, Development and Evaluation; PIONEER AF-PCI = Open-Label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention; RD = risk difference; RE-DUAL PCI = Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran vs. Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.

Figure 4.

Effect of dual versus triple therapy on major adverse cardiovascular events (top) and stroke (bottom). AUGUSTUS = Open-Label, 2 × 2 Factorial, Randomized Controlled, Clinical Trial to Evaluate the Safety of Apixaban vs. Vitamin K Antagonist and Aspirin vs. Aspirin Placebo in Patients With Atrial Fibrillation and Acute Coronary Syndrome or Percutaneous Coronary Intervention; ENTRUST-AF PCI = Edoxaban Treatment Versus Vitamin K Antagonist in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention; GRADE = Grading of Recommendations Assessment, Development and Evaluation; PIONEER AF-PCI = Open-Label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention; RD = risk difference; RE-DUAL PCI = Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran vs. Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.