NOACs Linked to Lower Stroke Risk Compared to Warfarin

Non‐vitamin‐K oral anticoagulants (NOACs) have been observed to be associated with a lower risk of both fatal and disabling, as well as non-disabling, stroke compared to warfarin.

Those given NOACs had no difference in the cases of fatalities due to stroke (odds ratio [OR], 0.90; 95% CI, 0.75—1.13; I² = 0%), with a point estimate in favor of them compared to warfarin. Meta-analysis revealed significantly superior data for NOACs (OR, 0.77; 95% CI, 0.66—0.89; I² = 21%) for fatal or disabling stroke as well as nondisabling stroke (OR, 0.85; 95% CI, 0.73—0.98; I²= 2%).

The review consisted of 5 phase 3 randomized controlled trials of NOACs— ARISTOTLE, ENGAGE-AF-TIMI 48, RE-LY, ROCKET AF, and SPORTIF V—conducted by Michelle Canavan, PhD, HRB Clinical Research Facility, National University of Ireland, and colleagues. The trials included 75,512 participants, of which 44,321 were randomized to NOACs and 31,191 were randomized to warfarin.

“This study suggests that optimally prescribed NOACs are associated with a lower risk of fatal, disabling or non-disabling stroke compared to warfarin,” Canavan and colleagues wrote. “Further study is required to identify if this reduction in stroke severity in NOACs compared to warfarin is seen in ischemic stroke populations.”

In 4 of the trials, NOACs were evaluated how they are usually prescribed, with acute stroke reported in 1403 (1.86%) participants in total, of which 787 (1.04%) were in the NOAC group and 616 (0.82%) in the warfarin group. In the NOAC group, 386 (0.51%) had a fatal or disabling stroke, while 401 (0.53%) had nondisabling. In the warfarin group, 367 (0.49%) experienced fatal or disabling, 249 (0.33%) had non-disabling stroke.

In total, 1170 fatal or disabling strokes were reported, of which the 666 participants (0.88%) were NOAC patients compared to 504 (0.67%) warfarin patients (OR, 8.6; 95% CI, 0.76—0.97; I² = 51%). The relative risk reduction (RRR) was 0.07% , absolute risk reduction (ARR) was 0.11%, and number needed to treat (NNT) 884.

When analyzing fatal or disabling strokes alongside the total number of strokes (n = 2393; 3.17% of total participants) there was no significant difference between the groups (OR, 0.98; 95% CI, 0.83—1.16; I² = 0%).

“Although we speculated that NOACs may have a lesser effect on severe stroke, compared to warfarin, our findings refuted our hypothesis,” Canavan and colleagues noted. “Our analysis suggests that there may be a greater reduction in stroke severity in those appropriately prescribed NOAC therapy compared to warfarin.”

Follow up revealed 1213 cases of non-disabling stroke (1.6% of total participants; 50.7% of all strokes), with no significant difference demonstrated in nondisabling strokes among participants randomized to NOAC (0.93%; n = 706) compared to warfarin (0.67%; n = 507), for an OR of 0.92 (95% CI, 0.82—1.04; I² = 21%). The RRR was 0.11%, ARR was 0.17% and NNT was 590—when assessed among the total number of strokes, there was no significant difference demonstrated between the 2 groups (OR 1.05; 95% CI, 0.89—1.24; I² = 6%).

Additionally, case fatality similar between groups, with the NOAC group reporting a rate of 18.6% (n = 444) compared to warfarin’s 14.2% (n = 341) for an OR of 0.90 (95% CI, 0.75—1.09; I² = 18%).

In the context of intracranial hemorrhage (ICH), prior meta‐analysis has suggested that NOAC anticoagulation can lower the risk of compared to warfarin. Across the 5 trials included in this assessment, 2613 ischemic strokes and hemorrhages were reported, of which 26.83% (n = 701) were ICH events and 73.17% (n = 1912) were ischemic events. The NOAC group reported ICH in 39.09% (n = 274) of patients compared to 60.91% (n = 427) in the warfarin group. Of the ischemic events, 61.87% (n = 1183) were in the NOAC group and 38.13% (n = 729) were in the warfarin group.

“Our meta-analysis supports the favorable trend towards NOACs not only in stroke fatality but in stroke severity,” the authors detailed. “We recognize that although our findings were significant the low ARR and high NNT indicate that further targeted research is needed, and certainly the impact of reversal agents and antidotes on stroke associated disability will be of great relevance in this field.”

REFERENCE

Costello M, Murphy R, Judge C, et al. Effect of non‐vitamin‐K oral anticoagulants on stroke severity compared to warfarin: a meta‐analysis of randomized controlled trials. Eur J Neurol. Published online November 27, 2019. doi: 10.1111/ene.14134.