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For acute ischemic strokes, early treatment with ticagrelor (Brilinta) and aspirin was better than aspirin alone for secondary prevention, the THALES trial showed.

In people with mild-to-moderate acute ischemic stroke or transient ischemic attack (TIA), the composite outcome of stroke or death in the 30 days after randomization favored a 30-day regimen of ticagrelor plus aspirin over aspirin alone (5.5% vs 6.6%, HR 0.83, 95% CI 0.71-0.96).

This was driven by fewer ischemic strokes (5.0% vs 6.3%, HR 0.79, 95% CI 0.68-0.93), with no significant difference in mortality rates between groups (0.7% vs 0.5%, HR 1.33, 95% CI 0.81-2.19). Disability rates didn't differ significantly.

The dual antiplatelet group experienced more severe bleeding by GUSTO criteria (0.5% vs 0.1%, HR 3.99, 95% CI 1.74-9.14) and more intracranial hemorrhage (0.4% vs 0.1%, HR 3.33, 95% CI 1.34-8.28), reported the investigators, led by S. Claiborne Johnston, MD, PhD, of Dell Medical School of the University of Texas at Austin.

A full manuscript of the study was published in the July 16 issue of the . Topline data were by trial sponsor AstraZeneca.

"The benefit from treatment with ticagrelor-aspirin as compared with aspirin alone would be expected to result in a number needed to treat of 92 to prevent one primary-outcome event and a number needed to harm of 263 for severe bleeding," the researchers concluded.

"Based on these results, plus the higher severe bleeding with ticagrelor, and greater expense, I don't think ticagrelor will replace clopidogrel [Plavix] as part of the dual antiplatelet regimen used after high risk TIA or minor stroke," commented James Grotta, MD, of Memorial Hermann-Texas Medical Center in Houston.

The directly comparing ticagrelor against clopidogrel as the add-on to aspirin is ongoing. Until then, it is "hard to compare" these drugs without a head-to-head comparison, Grotta said.

Nevertheless, the and CHANCE studies suggested larger relative reductions in the risk of recurrent ischemic stroke with clopidogrel-aspirin compared to THALES' ticagrelor-aspirin, according to Peter Rothwell, MD, PhD, of University of Oxford, England, writing in an .

Moreover, the risk in major bleeding was increased to a greater extent with the ticagrelor combination than the clopidogrel one, particularly with respect to intracranial hemorrhage, Rothwell continued.

Finally, clopidogrel-aspirin resulted in a significant reduction in risk of disabling or fatal stroke versus aspirin alone in a pooled analysis of the POINT and CHANCE trials, whereas ticagrelor-aspirin did not achieve the same in THALES, he noted.

Grotta said he would have expected the ticagrelor-aspirin combination to have produced greater benefit over aspirin than what was seen with clopidogrel-aspirin given the for clopidogrel response.

"Regardless of which combination of antiplatelet drugs is favored for the high-risk minority, all patients should receive aspirin immediately after TIA unless aspirin is contraindicated. Too many patients are sent home from emergency departments without this simple treatment that substantially reduces the risk and severity of early recurrent stroke," Rothwell urged.

included 11,016 participants who presented with acute ischemic stroke (NIH Stroke Scale score 5 or less) or high-risk TIA at 414 sites in 28 countries who were not undergoing thrombolysis or thrombectomy.

People were randomized within 24 hours after symptom onset. They either received a 30-day regimen of ticagrelor (180-mg loading dose, followed by 90 mg twice daily) plus aspirin (300-325 mg on the first day, followed by 75-100 mg daily) or matching placebo plus aspirin.

Baseline characteristics were similar between study arms. Mean age was 65 years, and 39% of the participants were women.

People already on aspirin before their index stroke or TIA accounted for 13% of the group.

Johnston and colleagues noted the limited generalizability of THALES to excluded populations, namely those with more severe strokes, cardioembolic strokes, and people who had treatment initiated more than 24 hours after symptom onset. Patients with a history of atrial fibrillation were also excluded.

"The bleeding risk associated with ticagrelor and aspirin might exceed the benefit among lower-risk patients who make up the majority in practice, and so the current trial results should not be overgeneralized," Rothwell cautioned.

Ticagrelor was first approved by the FDA in 2011 for the indication of thrombotic event risk reduction in people with acute coronary syndrome.

Last month, the P2Y12 inhibitor won an expanded indication to reduce risk of a first heart attack or stroke in high-risk patients with coronary artery disease.

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