Edoxaban Looks Good for Asians With A-fib in Real-world Analysis

The NOAC topped warfarin for safety and efficacy, with one expert saying the study boosts confidence for edoxaban in this population.

Edoxaban Looks Good for Asians With A-fib in Real-world Analysis

Edoxaban is associated with better efficacy and safety when compared with warfarin for stroke prevention in Korean individuals, an analysis of health claims data indicates.

New users of the once-daily non-vitamin K antagonist oral anticoagulant (NOAC) had lower risks of ischemic stroke, all-cause death, intracranial hemorrhage (ICH), and hospitalizations for GI or major bleeding over fairly limited follow-up, according to researchers led by So-Ryoung Lee, MD (Soon Chun Hyang University Hospital Seoul, Korea).

Those results were generally consistent across various subgroups, they report in a study published online ahead of the August 21, 2018, issue of the Journal of the American College of Cardiology. Of note, edoxaban did not appear to perform any worse in patients with a creatinine clearance above 95 mL/min, who the US Food and Drug Administration says should not receive the drug due to the potential for reduced efficacy.

“Additional studies are necessary to assess the effectiveness and safety of various edoxaban dose regimens in subgroups of Asian patients defined by age, sex, renal function, and frequently encountered comorbidities,” Lee et al write.

The study suggests greater benefits from using edoxaban than were found in the pivotal ENGAGE AF-TIMI 48 trial, which showed that the NOAC was noninferior to warfarin in terms of preventing stroke or systemic embolism and superior in terms of lowering risks of major bleeding and cardiovascular death.

Peter Kowey, MD (Lankenau Medical Center, Wynnewood, PA), who was not involved in the study, told TCTMD that the intrinsic limitations of observational studies, like residual confounding, need to be taken into account when interpreting the results. In particular, he said, propensity matching—which was used by Lee et al—cannot fully compensate for factors that go into a physician’s choice of one agent over another.

That said, there probably is some advantage to using edoxaban over warfarin in patients with A-fib, Lowey told TCTMD, adding that he was not surprised to see differences in ischemic stroke and bleeding.

Doctors should integrate information both from randomized clinical trials and robust real-world data sets when making treatment decisions, he said.

“I think you can gain some confidence from these kinds of experiences that edoxaban is going to behave pretty well in this population,” Kowey said. “You can’t make any argument here that it’s any worse than warfarin and it appears in some of the analyses to be better. Given what we learned from ENGAGE, if you supplement this information with that information, I think it should give people a lot of encouragement that this is a good drug.”

Missing Real-world Data

Asian patients have been underrepresented in the pivotal NOAC trials, and although subsequent real-world studies have suggested that the agents are safe and effective in Asian populations, there has been a lack of such analyses for edoxaban (Savaysa; Daiichi Sankyo), the fourth NOAC to come to market in the United States after dabigatran (Pradaxa; Boehringer Ingelheim), rivaroxaban (Xarelto; Bayer/Janssen), and apixaban (Eliquis; Bristol-Myers Squibb).

For the current study, Lee and colleagues examined claims data from the Korean National Health Insurance Service database on patients with A-fib starting anticoagulation between 2014 and 2016. After propensity matching, the analysis included 4,061 edoxaban users and 12,183 warfarin users. Overall, the median age was 72 and the median CHA2DS2-VASc score was 3.

During a median follow-up of 0.3 years for edoxaban users and 0.9 years for warfarin users, edoxaban was associated with lower risks of all six efficacy and safety outcomes examined.

Outcomes After Propensity Matching

 

Edoxabana

(n = 4,061)

Warfarina

(n = 12,183)

HR (95% CI)

Ischemic Stroke

3.22

3.89

0.69 (0.49-0.96)

All-Cause Death

5.59

6.63

0.72 (0.55-0.92)

ICH

0.66

1.59

0.41 (0.18-0.79)

GI Bleeding

1.65

2.02

0.60 (0.36-0.93)

Major Bleeding

2.32

3.56

0.53 (0.35-0.77)

Ischemic Stroke/ICH/All-Cause Death

8.90

11.20

0.67 (0.54-0.81)

aRates per 100 person-years.

Two different doses of edoxaban—30 or 60 mg once daily—were used in the study, with 56% of patients receiving the lower dose. The researchers evaluated outcomes of each versus warfarin. Rates of all of the outcomes favored edoxaban regardless of dose, although not all of the differences reached statistical significance after propensity matching.

Randomized vs Observational Data

The authors say the findings may differ somewhat from those of ENGAGE AF-TIMI 48 because of the inclusion of only Asian patients, who have a smaller average body size than Western patients. In addition, warfarin control has been shown in other studies to be worse in Asian versus Western populations, which could have made edoxaban look better in the various comparisons.

Kowey noted that there have been lingering questions about whether Asians differ from Caucasians in how they metabolize drugs and in their drug requirements, with some researchers, especially from Japan, arguing that Asians don’t need to use anticoagulant doses as high as those used by people of other races and ethnicities.

This has not been confirmed, but it is possible that the greater benefits seen in this analysis relative to ENGAGE AF-TIMI 48 could be related to higher drug exposure in this Asian patient population, Kowey said.

He pointed out that information like this from observational analyses—which doctors are going to see more and more of in the future—should be considered supplementary to data from randomized trials. “They’re both pieces of evidence that doctors can process when they’re making a decision about what anticoagulant they want to use,” he said.

In an accompanying editorial, Shinya Goto, MD, PhD, and Shinichi Goto, MD, PhD (Tokai University School of Medicine, Isehara, Japan), also highlight the complementary role these analyses can play.

“Lee et al’s data provide an important opportunity to validate the global trial results in a regional ‘real-world’ setting,” they write. “This type of regional validation of global trials in East Asia is important due to the perception that East Asian patients differ from other patient populations with regard to the use of anticoagulants.”

 

Sources
Disclosures
  • The study was supported by the Korean National Research Foundation of Korea funded by the Ministry of Education, Science, Technology and the Korean Healthcare Technology R&D project funded by the Ministry of Health & Welfare and sponsored by Daiichi Sankyo.
  • Lee and Shinichi Goto report no relevant conflicts of interest.
  • Shinya Goto reports having received a Grant-in-Aid for Scientific Research in Japan; having received a contracted research grant from Ono and independent research grants from Sanofi, Bristol-Myers Squibb, Pfizer, Astellas, and Daiichi Sankyo; having served as a member of the data safety committee for the ENGAGE AF-TIMI 48 trial; and serving as an associate editor for Circulation.
  • Kowey reports having consulted for all of the major manufacturers of oral anticoagulants, including Daiichi Sankyo.

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