Ticagrelor Doesn’t Beat Aspirin for Secondary Prevention After Stroke-TIA: SOCRATES

For patients with nonsevere acute ischemic strokes or high-risk transient ischemic attacks (TIAs), taking ticagrelor does not reduce the rate of stroke, MI, or death compared with aspirin through 90 days of treatment, the SOCRATES trial has found.

Although ticagrelor was shown to be well tolerated in this patient population, with no increase in bleeding relative to aspirin, there is no suggestion that it should be used as an alternative treatment, lead author S. Claiborne Johnston, MD, PhD (University of Texas at Austin), told TCTMD.

“We don’t have evidence that we should do that based on the way the trial was designed,” said Johnston, who reported the results at the European Stroke Organisation Conference in Barcelona, Spain. The findings were published simultaneously online in the New England Journal of Medicine.

Larry Goldstein, MD (University of Kentucky, Lexington), who commented on the study for TCTMD, agreed that ticagrelor should not be used in this setting based on these neutral results, pointing out that aspirin costs just “pennies a day.”

“It’s certainly disappointing that a different approach didn’t lead to improved patient outcomes, which is why we do these things,” Goldstein said.

One positive aspect, however, is that ticagrelor did not increase major bleeding, which has been a problem with some of the other more aggressive antiplatelet regimens, he said.

Need for Therapies to Reduce Residual Risk

Aspirin is commonly used for secondary prevention after ischemic stroke or TIA, but the rate of recurrent stroke remains high at about 10% to 15% through the first 90 days. Over the long term, aspirin—which carries risks of bleeding and adverse GI effects—cuts the rate of new ischemic events by only 22% compared with no treatment, highlighting the need for more effective strategies.

The SOCRATES trial, which was conducted at 674 centers in 33 countries, compared ticagrelor (Brilinta; AstraZeneca) and aspirin monotherapy in 13,199 patients with nonsevere, noncardioembolic acute ischemic stroke or high-risk TIA who had not received thrombolytic therapy and could be randomized within 24 hours of symptom onset. Ticagrelor was administered as a 180-mg loading dose followed by 90 mg twice daily through 90 days. Aspirin was given as a 300-mg loading dose followed by 100 mg daily.

Through 90 days, the rate of any stroke, MI, or death (primary endpoint) was 6.7% with ticagrelor and 7.5% with aspirin (HR 0.89; 95% CI 0.78-1.01), and that finding was consistent across patient subgroups.

The main secondary endpoint was ischemic stroke, and there was a marginally significant difference favoring ticagrelor (5.8% vs 6.7%; HR 0.87; 95% CI 0.76-1.00). All stroke also occurred at a lower rate with ticagrelor (5.9% vs 6.8%; HR 0.86; 95% CI 0.75-0.99). However, because the primary endpoint of the trial did not show a significant difference between the arms, the analyses of secondary endpoints should be considered exploratory, researchers said.

Although efficacy was not shown, ticagrelor proved to be safe, with no differences between the ticagrelor and aspirin arms in terms of major bleeding (0.5% vs 0.6%), intracranial hemorrhage (0.2% vs 0.3%), and fatal bleeding (0.1% in each group). All other major safety endpoints were similar in both groups, although dyspnea—a known side effect of ticagrelor—occurred more frequently in patients taking that drug (6.2% vs 1.4%).

Hint of Benefit?

While there were no significant interactions identified in subgroup analyses, there appeared to be an advantage for ticagrelor among patients who were taking aspirin at the time of their event (about one-third of trial participants). Because it takes several days for aspirin’s effects to wear off, patients assigned to ticagrelor in that subgroup were effectively taking dual antiplatelet therapy for a short period of time.

Johnston said that suggests that patients already taking aspirin when they have a stroke or TIA “may be a group that someone should evaluate further. Again, I’m not making any recommendations that anybody with acute stroke or TIA be treated with ticagrelor. This trial does not support that. But it’s just intriguing to think about whether follow-up studies should be done with specific subgroups.”

Related Stories:

• PLATO Substudy: ACS Patients with Prior Stroke at No Disadvantage with Ticagrelor
• After Minor Stroke/TIA, Dual Antiplatelet Therapy Reduces Recurrent Stroke vs. Aspirin
• Ischemic Stroke Patients on Prior Antiplatelet Therapy Fare Better After Thrombolysis