Brilinta (ticagrelor)

Approved: July 20, 2011 ^[1]

Brilinta is a reversible inhibitor of platelet aggregation and works by binding to the adenosine diphosphate (ADP) P2Y₁₂ receptor on the surface of the platelets ^[2] . The PLATO trial demonstrated Brilinta superiority over Plavix in heart attack and death prevention.  This, however, was seen when Brilinta was combined with aspirin doses of <100 mg ^[3].  One stipulation of Brilinta’s approval was a boxed warning mandated by the FDA stating: “Maintenance doses of aspirin above 100 mg reduce the effectiveness of Brilinta ^[2]”.   

Brilinta is the first reversible oral P2Y₁₂ receptor antagonist.  The irreversible binding of Plavix exhibits in a slow offset with a gradual recovery of platelet function.  Consequently, the effects of Plavix will last about 3-5 days after the drug is stopped due to the lifetime of the platelets ^[4]. Plavix is a prodrug that requires a two-step metabolic conversion to its active metabolite. Due to this process, the onset of action is relatively slow.  In contrast, Brilinta is not a prodrug and does not require metabolic activation to inhibit the P2Y₁₂ receptor.  Both Brilinta and Plavix undergo metabolism by CYP enzymes, resulting in formation of additional active metabolites.  Plavix is primarily metabolized through 2C19 whereas Brilinta uses the more common 3A4 pathway.  Involvement of the 3A4 pathway increases the risk for statin related adverse effects with doses of more than 40mg a day of either simvastatin or lovastatin. Monitoring of patient’s digoxin levels while on Brilinta is extremely important to avoid possible digoxin toxicity with initiation or change in Brilinta therapy ^{[2], [5]}. The most common non hemorrhagic event was dyspnea.  This was significantly higher than Plavix (13.8% versus 7.8%) ^[3][6].  The PLATO study showed that acute coronary syndrome patients treated with Brilinta had significantly decreased rates of death from vascular causes, myocardial infarction, or stroke versus Plavix ^[3][6].  The rates of major bleeding were not different between the two treatment groups.  However, there were significantly more patients in the Birlinta group with intracranial bleeding (p=0.06) ^[3][6]. Plavix has more convenient once daily dosing and is also ~ 20% cheaper.  Plavix costs around $5.66/ day and Brilinta around $7.24/day^[7].   

Will Brilinta find a place in therapy? Time will tell with the generic of Plavix, clopidogrel, due out in May of 2012 after being granted an additional 6 months to their patent due to pediatric exclusivity ^[8] .

1. "Brilinta." Daily Med. NIH, 20 July 2011. Web. 8 Aug. 2011.
2. "Brilinta." FDA. US Department of Health and Human Services, July 2011. Web. 8 Aug. 2011.
3. James, S., A. Akerblom, C. P. Cannon, et. al. "Comparison of Ticagrelor, the First Reversible Oral P2Y(12) Receptor Antagonist, with Clopidogrel in Patients with Acute Coronary Syndromes: Rationale, Design, and Baseline Characteristics of the PLATelet Inhibition and Patient Outcomes (PLATO) Trial." American Heart Journal 157.4 (2009): 599-605. Print.
4. Goodman, Louis S., Alfred Gilman, Laurence L. Brunton, John S. Lazo, and Keith L. Parker. "Clopidogrel." Goodman & Gilman's the Pharmacological Basis of Therapeutics. 11th ed. New York: McGraw-Hill, 2006. 1483. Print.
5. "Plavix." DailyMed. FDA, Sept. 2009. Web. 08 Aug. 2011.
6. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009;361:1045-57.
7. "AstraZeneca's Brilinta Drug Priced Above Plavix In US - WSJ.com." Business News & Financial News - The Wall Street Journal - Wsj.com. Wall Street Journal, 28 July 2011. Web. 08 Aug. 2011.
8. Bristol-Myers Squibb and Sanofi-aventis Announce U.S. FDA Decision to Grant Pediatric Exclusivity For PLAVIX®. Bristol-Myers Squibb. 25 Jan. 2011. Web. 8 Aug. 2011.