Rivaroxaban Monotherapy for Atrial Fibrillation in Coronary Artery Disease Patients
By Michael H. Crawford, MD, Editor
SYNOPSIS: For patients with atrial fibrillation and stable coronary artery disease, monotherapy was superior to dual therapy for preventing thrombotic and bleeding events and was associated with a lower mortality.
SOURCE: Naito R, Miyauchi K, Yasuda S, et al. Rivaroxaban monotherapy vs combination therapy with antiplatelets on total thrombotic and bleeding events in atrial fibrillation with stable coronary artery disease: A post hoc secondary analysis of the AFIRE trial. JAMA Cardiol 2022; Jun 15. doi: 10.1001/jamacardio.2022.1561. [Online ahead of print].
Investigators in Japan conducted the atrial fibrillation and ischemic events with rivaroxaban in patients with stable coronary artery disease (AFIRE) trial. For patients with AF and coronary artery disease (CAD), rivaroxaban monotherapy was associated with a lower risk of the first cardiovascular event and major bleeding event vs. standard combination therapy with an antiplatelet agent. However, subsequent clinical events were not taken into account, so the true burden of disease was not captured.
The aim of this post hoc secondary analysis of AFIRE was to test the hypothesis that rivaroxaban alone compared to combination therapy with an antiplatelet drug was associated with a lower incidence of total cardiovascular or bleeding events in patients with AF, CAD, and a CHADS2 score of 1 or higher. The authors excluded patients with stent thrombosis or poorly controlled blood pressure. Rivaroxaban 15 mg was given daily to those with a creatinine clearance of 50 mL/min or more and 10 mg/day to those with 15 mL/min to 49 mL/min. Antiplatelet medication could be either aspirin or a P2Y12 agent. The primary endpoint was the number of total bleeding and thrombotic events. The former included major bleeding and hemorrhagic stroke; the latter included ischemic stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause.
Between 2015 and 2017, researchers recruited 2,215 patients into the intention-to-treat cohort (mean age, 74 years; 21% women). They experienced 348 events (78% first events, 22% subsequent events over a 24-month follow-up. Total events on rivaroxaban monotherapy occurred in 12% vs. 19% on combination therapy (HR, 0.62; 95% CI, 0.48-0.80; P < 0.001). Total mortality was 3.7% on monotherapy and 6.6% on combination therapy (HR, 0.57; 95%CI, 0.39-0.83; P = 0.004). Thrombotic events were more frequent as first events (4.1%) vs. bleeding and mortality (3% for each). Bleeding was more common as a second event (6% vs. 4.5% for thrombosis and 4% for mortality). The authors concluded that for patients with AF and stable CAD, rivaroxaban monotherapy was associated with lower risks of thrombotic and bleeding events than combination therapy with an antiplatelet agent and was associated with a lower mortality rate. Eventual tapering of antiplatelet therapy in favor of antithrombic monotherapy should be considered for stable CAD patients.
This secondary analysis of the AFIRE study confirms the original conclusion that rivaroxaban monotherapy is superior to combination therapy with an antiplatelet drug for lowering the risk of cardiovascular and bleeding events. In fact, the AFIRE study ended prematurely because of the higher mortality rate in the combination group. Interestingly, the risk of death was higher as a proportion of subsequent events (48%) vs. first events (28%). Thus, death probably was underestimated in AFIRE. Also, AFIRE demonstrated mortality rates are higher with bleeding events vs. thrombotic events.
Today, many clinicians might elect to abandon triple therapy in AF post-percutaneous coronary intervention (PCI) patients at some point during the first-year after PCI. The timing depends on the risk of thrombotic events in each particular patient. Perhaps this logic should be applied to the decision for mono vs. dual therapy in each stable CAD patient. The only problem with that approach is there are not well-accepted methods for determining thrombotic event risk in stable CAD patients. After the acute phase of a CAD event, bleeding becomes progressively more of an issue compared to a thrombotic event, and bleeding is associated with a higher mortality rate than subsequent thrombotic events. Thus, even dual therapy, let alone triple therapy, becomes an issue regarding bleeding risk as more time passes. As thrombotic risk decreases, more attention to bleeding risk is warranted. The challenge is deciding when the transitions should occur. Currently, the best approach is shared decision-making with patients. Clinicians should consider all the risks associated with CAD and AF, along with the risk of the drugs and the available trial data.
For patients with atrial fibrillation and stable coronary artery disease, rivaroxaban monotherapy was superior to dual therapy for preventing thrombotic and bleeding events and was associated with a lower mortality.
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