DOACs Good for Secondary Prevention in Older A-fib Patients, Real-world Numbers Affirm

Older patients with A-fib who are discharged after an acute ischemic stroke fare better when they’re started on a direct oral anticoagulant (DOAC) rather than warfarin, new real-world data show, providing support for the preference given to the newer agents in clinical guidelines.

Stroke survivors who received a DOAC at discharge had a greater number of days spent at home and out of a hospital or skilled nursing facility in the year after their event (mean 287.2 vs 263.0 days; adjusted difference 15.6 days), as well as a lower MACE risk during follow-up (34.0% vs 40.4% per year; adjusted HR 0.89; 99% CI 0.83-0.96), researchers led by Ying Xian, MD, PhD (Duke Clinical Research Institute, Durham, NC), report.

Several secondary outcomes also favored DOAC treatment, which was dinged only by a slightly higher risk of GI bleeding compared with warfarin therapy (5.4% vs 5.1% per year; adjusted HR 1.14; 95% CI 1.01-1.30).

The study, published online July 22, 2019, in JAMA Neurology, “provides some real-world evidence that those DOACs are actually working pretty well in community practice,” Xian told TCTMD, noting that their benefits across a variety of endpoints outweigh the increased risk of GI bleeding.

Thus, these results support advice in practice guidelines to go with DOACs over warfarin in most scenarios, Xian said: “The findings from our study actually provide additional evidence that DOACs should be considered as the first-line [treatment] over warfarin, at least for secondary stroke prevention.” That, he added, is dependent on the patient’s ability to pay, because “of course, those DOACs are more expensive than warfarin.”

Jonathan Piccini, MD (Duke Clinical Research Institute), who was not involved in the study, noted that controversy surrounded the DOACs when they first came out, with concerns raised about the methodology of the pivotal trials, the quality of the warfarin therapy in the control arms, increases in GI bleeding, and the lack of antidotes.

“And yet, study after study after study has shown that these medications lead to substantial benefit, and I think that most providers, if you ask them—‘If you had a family member with atrial fibrillation who required stroke prevention therapy, would you want them to be on warfarin or a direct-acting oral anticoagulant?’—I think it’s pretty clear that a direct oral anticoagulant is a much better therapy,” Piccini said.

He pointed out that the benefits of DOACs are particularly pronounced in older patients, who have greater overall risks of both ischemic and bleeding events.

“There have been lots of studies that have shown that one of the most potent predictors of intracranial bleeding is age, so if you’re going to recommend a drug [whose] primary benefit is a significant reduction in intracranial bleeding, yes, the elderly is exactly the patient population that you would expect to benefit,” Piccini said.

Focusing on Patient-Centered Outcomes

The pivotal trials showed that DOACs are at least as good as warfarin when it comes to stroke prevention, findings that have been replicated in subsequent real-world studies. Much of that confirmatory research, however, has been done using administrative claims data and has not focused on patient-centered outcomes, Xian said.

To overcome some of those issues, he and his colleagues turned to the PROSPER study, which is based on the Get With The Guidelines-Stroke clinical registry from the American Heart Association/American Stroke Association. The researchers also pulled in Medicare claims data. This analysis included 11,662 patients who had A-fib, were discharged from one of 1,041 hospitals after an acute ischemic stroke between October 2011 and December 2014, and were newly started on oral anticoagulation. Median patient age was 80, and more than half (56.3%) were women.

Overall, 34.7% of patients were discharged on a DOAC, which at the time included dabigatran (Pradaxa; Boehringer Ingelheim), rivaroxaban (Xarelto; Bayer/Janssen), and apixaban (Eliquis; Bristol-Myers Squibb). The rest received warfarin. Patient characteristics were mostly similar in the two groups, except for lower median stroke severity and unemployment in the DOAC-treated cohort.

After using propensity score-overlap weighting to adjust for differences between groups, the investigators found that outcomes favored DOAC treatment. In addition to more time spent at home and a lower MACE risk, patients who received one of the newer agents instead of warfarin also had lower risks of all-cause death, all-cause and CV readmission, hemorrhagic stroke, and hospitalization with bleeding. GI bleeding was more frequent with DOAC treatment, but there were no differences in fatal bleeding, ischemic stroke readmission, or systemic embolism.

“Overall, these findings indicate that DOACs have a favorable risk-benefit profile compared with warfarin for secondary prevention in patients with ischemic stroke and atrial fibrillation,” the authors write.

Piccini said the findings are consistent with the prior randomized trials testing DOACs versus warfarin.

In the future, Xian said, it would be helpful to break the findings down further by type of DOAC in order to better inform treatment choices for patients with A-fib who have had a stroke.