Headline: Brilinta Reduces Death Rates vs. Plavix in Acute Coronary Syndrome!
Tagline: But Not By Much, and at a High Cost.
July 20, 2011 AstraZenica received FDA approval for their new antiplatelet agent Brilinta (ticagrelor) for use in acute coronary syndrome. Brilinta joins an increasingly crowded market of antiplatelet agents that includes the longstanding leader in the class Plavix and Effient, which came to market July 10, 2009. Effient has not become terribly popular, likely due to its higher rate of bleeding complications including life threatening bleeding and an increased incidence of stroke in patients with previous stroke. These risks seem to have held sway over the modestly reduce rate of restenosis of coronary artery stents seen in Effient vs. Plavix patients when used post coronar artery stent placement.
The primary selling point of Brilinta is that in the PLATO clinical trial the mortality rate in patients with acute coronary syndrome was stastically significantly lower in patient using Brilinta (9.8%) vs. Plavix (11.7%) P<0.001. Patients on Brilinta had lower death rates from heart attack and stroke, but had higher rates of non-fatal bleeding complications. The reversible mechanism of action of Brilinta has its drawbacks though, requiring twice daily dosing vs. daily dosing with Plavix.
The primary issue with Brilinta is whether this statistically significant reduction in death rates in acute coronary syndrome is practically significant, and whether the potential drawbacks of twice daily dosing and the non-compliance issues this may engender will erode those benefits when used for longer periods of time. When the Plavix patent expires soon and generic clopidogrel becomes available the benefits of Brilinta and its current high cost of $7.24/day will need to be enough to make that cost difference palatable. Plavix has been an effective, well tolerated and extremely popular drug. It is the third highest gross sales drug in the US (2009 data) and is anticipated to be available as an inexpensive generic in about May 2012.
These are some of the pros and cons that patients and physicians will need to consider when making a decision between Plavix and Brilinta
|Long track record and well understood||Slightly lower death rate in acute coronary syndrome|
|Currently less expensive than Brilinta, soon to be much less expensive after generic Plavix is available May 2012.||No hepatic metabolism needed|
|Once Daily Dosing||Can be used with proton pump inhibitors|
|Slightly less effective in acute coronary syndrome||Higher cost, soon to be much higher|
|Loses efficacy used with Proton Pump Inhibitors||Twice daily dosing may reduce compliance|
|New drug, after market side effects to be determined|
|Efficacy reduced with aspirin doses >100 mg daily|
Brilinta, like Plavix and Effient works as a platelet aggregation inhibitor, but acts with a slightly different mechanism of action, binding at a site different from the ADP receptor it blocks. It is a reversible receptor inhibitor, and Brilinta, unlike Plavix does not require hepatic activation which may be a potential advantage in some patients. The importance of the hepatic metabolism issue in overall efficacy is unclear, and this may be just a theoretic issue of little clinical significance.
Brilinta currently has a black box warning similar to that with Plavix warning against use in patients with active bleeding, a history of intracranial hemorrhage, and tha bleeding should be suspected in any patient with hypotension who has had a recent procedure like CABG, coronary angiography or any other surgery. Unlike Plavix the black box warning also includes an increased risk of cardiovascular events if Brilinta is discontinued, making the twice daily dosing and compliance an even larger concern. The black box warning also noted the reduced effectiveness of Brilinta if aspirin at doses higher than 100 mg daily are used. This could easily be done inadvertently in patients taking OTC aspirin products. If you do not personally have a history with Aspirin usage, consider this resource about aspirin side effects.
An unexpected issue with Brilinta is a much higher incidence of dyspnea (13%) vs Plavix (7%).
In summary I expect Brilinta to be a niche product used in uncommon circumstances once clopidogrel becomes available as an inexpensive generic.