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FDA granted ticagrelor (Brilinta) an indication for secondary prevention in stroke and high-risk transient ischemic attack (TIA), AstraZeneca announced.

The P2Y12 inhibitor is to be used as part of a dual antiplatelet regimen along with a daily maintenance dose of 75-100 mg aspirin for the reduction of recurrent stroke risk.

The expanded indication was based on the THALES trial, which was published in July in the New England Journal of Medicine.

In the trial with more than 11,000 participants, minor stroke and TIA patients randomized to ticagrelor plus aspirin had lower 30-day composite stroke and death rates than those randomized to aspirin alone (5.5% vs 6.6%, HR 0.83, 95% CI 0.71-0.96).

The benefit had been 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).

Ticagrelor did, however, lead to more severe bleeding (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).

THALES investigators estimated a number needed to treat (NNT) of 92 to prevent one stroke or death and a number needed to harm of 263 for severe bleeding.

"One in four patients who have had a stroke will experience a second one, with the risk particularly high within the first 30 days. The approval of Brilinta in combination with aspirin is an important advancement to reduce the risk of recurrent stroke and much-awaited good news for physicians and patients," said THALES lead investigator S. Claiborne Johnston, MD, PhD, of the University of Texas at Austin, in a .

Following FDA approval of the new indication, Johnston's group released a secondary analysis of THALES, which showed ticagrelor associated with fewer disabling strokes, from either the progression of the index event or a new stroke.

Incidence of recurrent disabling stroke (with modified Rankin Scale [mRS] scores 2+) or death at 30 days reached 4.0% in the ticagrelor plus aspirin group and 4.7% of those taking aspirin alone (HR 0.83, 95% CI 0.69-0.99).

The NNT was 133 to prevent one disabling stroke or death and 112 to prevent one disabling or fatal ischemic stroke, the investigators reported in in conjunction with presentation at the .

The reduction of disabling stroke was consistent across prespecified subgroups with the exception of people with diabetes. This finding may be due to chance or could reflect hypofibrinolysis in these individuals, Johnston and colleagues suggested.

Ticagrelor did not significantly reduce recurrent non-disabling strokes (mRS 0-1) or death at 30 days in the trial (1.3% vs 1.6%, HR 0.79, 95% CI 0.57-1.08).

Overall, treatment with ticagrelor was associated with less disability when recurrent strokes did occur. In patients with recurrent ischemic stroke, the resulting disability burden favored ticagrelor over aspirin alone (OR 0.77, 95% CI 0.65-0.91).

Independent predictors of recurrent disabling stroke were baseline NIH Stroke Scale score 4 to 5, ipsilateral stenosis of at least 30%, Asian race, older age, and higher systolic blood pressure.

Johnston's team cautioned that residual confounding was possible in the secondary analysis. There was also no disability assessment at day 90, though authors argued that 30-day mRS is highly correlated with 90-day mRS scores.

Ticagrelor's new indication for stroke prevention joins its other existing indications: reduction of risk of cardiovascular death, MI, and stroke in patients with acute coronary syndrome or a history of MI; and reduction of the risk of a first MI or stroke in high-risk patients with coronary artery disease.

Notably, ticagrelor is more expensive than clopidogrel (Plavix), another P2Y12 inhibitor used in secondary stroke prevention.

Unlike ticagrelor, however, clopidogrel did not significantly reduce disabling ischemic strokes when added to aspirin in the . It took a pooling of the CHANCE and POINT trials to suggest such a benefit, Johnston and colleagues noted.

The directly comparing the two P2Y12 inhibitors is ongoing.

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