Switching DOACs: The finer points in safety and efficacy from the ATHENS study

Direct oral anticoagulants (DOACs), such as apixaban and rivaroxaban, are commonly prescribed to mitigate risks of stroke and systemic embolism. This class of medications has a strong evidence base from clinical trials and real- world studies affirming their efficacy and safety.^1,2

However, due to various reasons, such as side effects, drug interactions, or idiosyncratic preferences, there are times when patients switch between these medications. Understanding the efficacy and safety of continuing versus switching between these drugs is vital for adequate anticoagulation and reducing complications like stroke and major bleeding events.³

The real-world study Assessment of Health and Economic Outcomes in NOAC Switchers (ATHENS) delved into the safety implications of continuing or switching between apixaban and rivaroxaban. Comparison of outcomes in patients who either continued or switched between these two anticoagulants provided key insights that can better inform patients and providers alike.³

The ATHENS Study

The ATHENS study was a large, real-world analysis designed to evaluate primary safety outcomes that included stroke or systemic embolism, and major bleeding events, including gastrointestinal (GI) bleeding, ischemic stroke, hemorrhagic stroke, and other major bleeding events in patients treated with apixaban or rivaroxaban. The study focused on four groups of patients: those who were on apixaban throughout the study, those who remained on rivaroxaban, and patients who switched between the two—either from apixaban to rivaroxaban or vice versa. Key findings from the study provided deep insights into the efficacy and safety of the two medications and the clinical implications of switching between them.3

Switching from Apixaban to Rivaroxaban

Compared to those who continued apixaban, patients who switched from apixaban to rivaroxaban were shown to have significantly higher risks of stroke and systemic embolism, specifically, ischemic and hemorrhagic stroke. These patients were also more prone to major bleeding events, including GI bleeding, than those who maintained apixaban.³ (See Table below)

                                                            Switching from Apixaban to Rivaroxaban vs Apixaban Continuers
 

‡Confidence Interval for SE was truncated.

Switching from Rivaroxaban to Apixaban

On the other hand, patients who started on rivaroxaban and shifted to apixaban had a similar risk of stroke and systemic embolism compared to those who continued rivaroxaban. Notably, those who switched from rivaroxaban to apixaban showed a lower risk of major bleeding, including GI and other major bleeding events.³ (See table below)


^{§Proper hazard ratio and confidence interval were not obtained due to one group having 0 event. There are no available head-to-head trials among DOACs, so direct comparisons cannot be made.}

Clinical Implications

Data from the ATHENS study shows that there are clinically significant efficacy and safety issues in switching between DOACs, specifically between apixaban and rivaroxaban. Such practice must be informed by a strong evidence base like the data from the ATHENS study and clinicians must be prudent in considering these in their clinical decision making.³

The ATHENS study highlights the value of maintaining, and switching to apixaban therapy, to minimize both stroke and bleeding risks, which should provide essential guidance for physicians and patients who need anticoagulation therapy, in navigating treatment decisions.³