Another NOAC Flops for Prevention After Cryptogenic Stroke

Dabigatran (Pradaxa) was no better than aspirin for secondary stroke prevention in non-lacunar cryptogenic strokes, the RE-SPECT ESUS trial showed.

Recurrent stroke rates came out similar for patients with a recent history of embolic stroke of undetermined source randomized to the non-vitamin K antagonist oral anticoagulant (NOAC) as for those on placebo (4.1% vs 4.8% per year, HR 0.85, 95% CI 0.69-1.03).

The same was observed for ischemic strokes (4.0% vs 4.7% per year, HR 0.84, 95% CI 0.68-1.03), reported researchers led by Hans-Christoph Diener, MD, PhD, of University Hospital Essen in Germany.

Whereas major bleeding was similarly likely between groups (1.7% vs 1.4% per year, HR 1.19, 95% CI 0.85-1.66), there were more clinically-relevant non-major bleeds with dabigatran (1.6% vs 0.9% per year, HR 1.73, 95% CI 1.17-2.54).

Data from the trial’s 19-month follow-up were published in the May 16 issue of the New England Journal of Medicine. Preliminary report of the results came out at the World Stroke Congress in 2018.

“Post hoc analysis suggested that dabigatran may have had an effect on stroke recurrence after 1 year, but no inferences can be made because of the post hoc nature of the analysis. A possible explanation for this temporal pattern might be a progressive increase in the occurrence of asymptomatic, undetected atrial fibrillation [Afib] and other cardiac sources of embolism over time,” Diener and colleagues noted.

Another NOAC, rivaroxaban (Xarelto), was also shown to be no better than aspirin in preventing recurrent strokes in a similar population in NAVIGATE ESUS.

The 5,390 adults randomized in RE-SPECT ESUS received either dabigatran (150 mg or 110 mg twice daily depending on age and kidney function) or aspirin (100 mg once daily).

Study participants had had non-lacunar ischemic strokes — with less than 50% stenosis in arteries supplying the territory, as well as no Afib lasting more than 6 minutes or any other identifiable source of emboli — in the 3 to 6 months prior to enrollment.

Mean age was 64.2 years, and 36.9% of the cohort were women.

Trial investigators reported similar baseline characteristics between groups, except the dabigatran group was 0.6 years older on average.

“In our trial, extended ECG monitoring after randomization was performed in only 14% of patients; therefore, we do not have a systematic assessment of the occurrence of atrial fibrillation,” Diener’s group acknowledged.

That said, the strengths of RE-SPECT ESUS included its large sample size and sufficient stroke events to match expectations from the power calculation for the trial, according to the investigators.

last updated 05.16.2019