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Brilinta OK'd for Primary Prevention

— FDA expands indication beyond THEMIS trial that provided the data

by Crystal Phend, Senior Editor, 鶹ý

MedpageToday
Ticagrelor (Brilinta) over a computer rendering of coronary artery disease above FDA APPROVED

Ticagrelor (Brilinta) gained an indication expansion to reduce risk of a first heart attack or stroke in high-risk patients with coronary artery disease, .

FDA approval centered on the , which showed that adding the potent antiplatelet agent to aspirin for 36 months reduced cardiovascular death, myocardial infarction (MI), or stroke compared with aspirin alone (7.7% vs 8.5%, HR 0.90, 95% CI 0.81-0.99).

While that trial enrolled type 2 diabetes patients with a prior percutaneous coronary intervention (PCI), bypass surgery, or at least a 50% narrowing of a coronary artery (but no prior MI or stroke), the new indication approved Monday wasn't limited to diabetes patients.

Ticagrelor previously had indications in acute coronary syndrome and in secondary prevention in high-risk people with a prior MI; this is the first indication for the drug in those without a history of heart attack or stroke.

AstraZeneca also recently announced that ticagrelor (at 90 mg vs the 60 mg used in THEMIS) plus aspirin reduced the 30-day composite risk of stroke and death after an acute ischemic stroke or transient ischemic attack in topline results from the phase III THALES trial.

When the THEMIS trial results were released last year at the European Society of Cardiology (ESC) meeting and online in the New England Journal of Medicine, concerns about clinical impact centered on the bleeding risk seen in the trial.

The extended dual antiplatelet regimen with ticagrelor significantly increased TIMI major bleeding (2.2% vs 1.0%, HR 2.32) and intracranial hemorrhage (0.7% vs 0.5%, HR 1.71) over aspirin alone, albeit without more fatal bleeding.

At the ESC session, study discussant Colin Baigent, MD, of Oxford University in England, actually calculated 12 major bleeds for every eight death, MI, or stroke events prevented.

Adding the bleeding and efficacy endpoint together into an exploratory composite outcome of "irreversible harm" yielded a neutral result.

However, the prespecified substudy in patients with a history of PCI -- THEMIS-PCI -- showed a larger benefit from ticagrelor for the efficacy endpoint (7.3% vs 8.6%, HR 0.85, P=0.013) that overcame the elevated bleeding risk to yield a significant 15% net clinical benefit in preventing irreversible harms.

That subgroup was not addressed in the .