O’Connor said genetic differences might also be at play, because African Americans more often harbor a gene variant that makes them less responsive to beta blockers than whites. His study was funded in part by ARCA biopharma, which is developing a genetically targeted beta blocker treatment.

Whatever the explanation for the geographical variation, it’s a problem drug developers would do well to tackle if they want their products to be approved by the U.S. Food and Drug Administration, according to O’Connor.

“This really goes beyond the beta blocker and heart failure story, it’s about how we conduct clinical trials,” he said. “I think the FDA gets nervous when they keep seeing these trends where, things may not look as good in the U.S.”

As a case in point, for a while it appeared the FDA might not approve drugmaker AstraZeneca’s new blood thinner Brilinta, because North American patients taking the drug did worse than patients on an older blood thinner - which wasn’t the case for European patients in the study.

AstraZeneca finally convinced the FDA the reason for the poorer results in North America might be related to the fact that aspirin interferes with Brilinta, and aspirin is more commonly used by heart patients in the U.S. than in Europe. The FDA approved Brilinta on July 21.

In an editorial in the same journal, Dr. Barry M. Massie, explains that many drug trials have now become “megatrials,” including several thousand patients in different countries.

That’s partly because current drugs and medical devices are so effective now that most advantages from new treatments will be miniscule. As a result, it requires lots of patients to show that potential benefits aren’t just a result of chance.

While Massie, of the VA Medical Center in San Francisco, calls the new findings “provocative,” he adds that American patients might still benefit from beta blockers.

“Most important, one cannot exclude the play of chance in these findings,” he writes.

SOURCE: Journal of the American College of Cardiology, online August 15, 2011.