A 55-year-old Caucasian male patient presented to the office for a follow-up visit. He was a former smoker with type 2 diabetes mellitus, hypertension, and hyperlipidemia who had an anterior wall myocardial infarction (MI) 15 months ago that was treated with percutaneous coronary intervention (PCI) with a drug-eluting stent to the left anterior descending artery. Non-obstructive coronary artery disease of the right coronary and left circumflex arteries was noted on the angiogram. He was also noted to have paroxysmal episodes of atrial fibrillation (AF) during the MI hospitalization. Echocardiography showed normal left ventricular systolic function. He was treated with aspirin 81 mg daily, ticagrelor 90 mg twice daily, and rivaroxaban 20 mg daily for the first month following the PCI, after which aspirin was discontinued. He did not have any hospitalizations since his initial presentation, and he has been compliant with his medical therapy. He does aerobic exercises for 1 hour 4 times a week without any limiting angina or dyspnea.
On exam, his BMI was 28, temperature was 98.6 °F, heart rate was 86 bpm, and blood pressure was 124/76 mmHg. The cardiovascular exam was otherwise unremarkable. His electrocardiogram (ECG) demonstrated normal sinus rhythm. Ambulatory ECG monitoring after the MI confirmed the presence of episodes of paroxysmal AF. His lipid panel showed a total cholesterol of 130 mg/dL: high-density lipoprotein of 42 mg/dL and low-density lipoprotein of 68 mg/dL. Hemoglobin A1c was 7.3%. His current medications were ticagrelor 90 mg twice daily, rivaroxaban 20 mg daily, metoprolol succinate 100 mg daily, atorvastatin 80 mg daily, metformin 1gm twice daily, and liraglutide.
Which of the following options would be the most appropriate choice of antithrombotic regimen for this patient in light of latest evidence?
The correct answer is: B. Stop ticagrelor and continue rivaroxaban monotherapy.
The PIONEER AF-PCI (An 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), 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), and AUGUSTUS (Antithrombotic Therapy After Acute Coronary Syndrome or PCI in Atrial Fibrillation) trialsstudying rivaroxaban, dabigatran, and apixaban, respectivelyhave all documented the safety of anticoagulation with a novel oral anticoagulant (OAC)/mono-antiplatelet therapy (dual therapy) in the first year after PCI in the setting of AF. The role of combination therapy with an anticoagulant and an antiplatelet agent for patients with stable ischemic heart disease (SIHD) and AF is not well established. Recent randomized controlled trial (RCT) results support antithrombotic monotherapy with an OAC in this population. An observational Danish registry-based study1 was the first to investigate this question, which was followed by the first RCT, the OAC-ALONE (Optimizing Antithrombotic Care in Patients with Atrial Fibrillation and Coronary Stent) trial.2 The OAC-ALONE trial failed to establish noninferiority of OAC alone compared with a regimen of OAC and single antiplatelet therapy because patient enrollment was prematurely terminated, leading to an underpowered sample size.2 More recent data from the AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial3,4 has shown clear noninferiority of rivaroxaban monotherapy compared to rivaroxaban plus an antiplatelet of choice (73% aspirin and 27% P2Y12 inhibitor) for patients with AF and SIHD at least 1 year after PCI or an acute coronary syndrome. Primary efficacy outcome was a composite of all-cause mortality, MI, stroke, unstable angina requiring revascularization, or systemic embolism. This study demonstrated superiority of rivaroxaban for major bleeding as the safety outcome and noninferiority for the efficacy outcome.
The other answer options presented are reasonable and are commonly used in clinical practice, but with the background of real-world data from the Danish study1 and RCT evidence from the OAC-ALONE2 and AFIRE4 trials, it is reasonable to consider OAC monotherapy in patients with AF and SIHD who are over 1 year from coronary revascularization or an acute coronary syndrome. The patient has paroxysmal AF with a CHA2DS2VASc score of 3 and therefore requires anticoagulation therapy. Only aspirin therapy is not appropriate (answer A). Many robust studies have shown efficacy and safety outcomes in favor of direct OACs compared to warfarin in patients with AF (answer E).5 Nevertheless, head-to-head clinical trials comparing warfarin therapy with direct OACs for AF with SIHD do not exist at this time. This patient has diabetes mellitus, which by itself is an indication for aspirin 81 mg daily per the present US Preventive Services Task Force guidelines given his additional risk factors for atherosclerotic vascular disease. But in the AFIRE trial,4 in predetermined subgroup analysis, monotherapy with rivaroxaban was noninferior to combination therapy with aspirin and rivaroxaban in patients with diabetes mellitus (answer C). There are no outcome data comparing apixaban with rivaroxaban in patients with SIHD with concomitant AF, so switching to apixaban to improve cardiovascular outcomes is not necessary at this time (answer D).5
Lamberts M, Gislason GH, Lip GY, et al. Antiplatelet therapy for stable coronary artery disease in atrial fibrillation patients taking an oral anticoagulant: a nationwide cohort study. Circulation 2014;129:1577-85.
Matsumura-Nakano Y, Shizuta S, Komasa A, et al. Open-Label Randomized Trial Comparing Oral Anticoagulation With and Without Single Antiplatelet Therapy in Patients With Atrial Fibrillation and Stable Coronary Artery Disease Beyond 1 Year After Coronary Stent Implantation. Circulation 2019;139:604-16.
Becker RC. Antithrombotic Therapy in Atrial Fibrillation and Coronary Artery Disease. N Engl J Med 2019;381:1169-70.
Yasuda S, Kaikita K, Akao M, et al. Antithrombotic Therapy for Atrial Fibrillation with Stable Coronary Disease. N Engl J Med 2019;381:1103-13.
Lopes RD, Heizer G, Aronson R, et al. Antithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation. N Engl J Med 2019;380:1509-24.