* Third of patients have gene variation that hampers drug
* Triple dose of clot preventer overcomes gene roadblock
By Lewis Krauskopf and Bill Berkrot
ORLANDO, Fla, Nov 16 High doses of the blood thinner Plavix can help heart patients overcome a common genetic variation that interferes with the widely used drug's anti-clotting effects, according to clinical data presented on Wednesday.
When doses were tripled or quadrupled, only 10 percent of patients with the gene variation did not respond, compared with half who failed to respond when given the common standard 75 milligram dose, according to a study released at the American Heart Association meeting in Orlando.
Almost one-third of the general population carries a variation in the CYP2C19 gene that makes it difficult to metabolize Plavix, known chemically as clopidogrel.
The data provide a "a rational framework for how to start to approach alternative dosing" for patients who have a "genetic roadblock," said Dr. Marc Sabatine, senior author of the study.
Plavix is the world's second-biggest-selling drug but is expected to lose U.S. patent protection next year, so the business implications may be minimal for manufacturers Bristol-Myers Squibb Co and Sanofi SA , which funded the study.
But the potential to use high doses of Plavix in this population with the genetic variation could hurt sales for newer rivals Effient, from Eli Lilly and Co , and Brilinta, from AstraZeneca Plc .
Lilly and Astra are expected to have a tougher time convincing doctors to use their drugs when cheaper generic versions of Plavix flood the market.
The study involved 335 patients who had suffered a heart attack or who had undergone procedures to open blocked heart vessels. Researchers found no significant increase in side effects as dosages increased.
But they cautioned the study was not designed to assess any clinical outcomes, only the effects on blood platelets.
Plavix prevents blood clots by blocking platelets from binding together in the blood.