A new study suggests Americans with heart failure may benefit less from recommended medications than patients in other countries.

The findings, which one doctor called “provocative,” point to an emerging problem in drug development: As research becomes increasingly international, the outcomes may be less dependable in individual countries.

In the new work, researchers drive that point home for drugs known as beta blockers, which gold-standard tests have shown can extend the life of people with heart failure.

Breaking those drug trials down by country, it turns out U.S. patients didn’t benefit appreciably, whereas the number of deaths during the trials fell by more than five in 100 in the rest of the world.

Lead researcher Dr. Christopher O’Connor, a cardiologist at Duke University Medical Center in Durham, North Carolina, said earlier studies had hinted of geographical differences in outcomes, but never as clearly as the new results.

Some five million Americans are living with heart failure, in which the heart fails to pump enough blood into the body. The condition is involved in about 300,000 deaths every year, according to the National Institutes of Health.

O’Connor’s study, released Monday in the Journal of the American College of Cardiology, represents the first sweeping look at how beta blocker trials may come to different conclusions depending on the nationality of the participants.

He and his colleagues pooled results from so-called randomized controlled trials - the strongest experimental design available to doctors - that included U.S. patients.

They found four trials - the MERIT-HF, the COPERNICUS, the CIBIS-2, and the BEST trials - with a total of some 9,000 participants, nearly half of them American.

During those studies, beta blockers cut deaths among non-U.S. patients by 36 percent, while there was no statistically reliable drop among U.S. patients.

While that doesn’t necessarily mean Americans don’t benefit at all, it does question heart failure treatment guidelines, which often rely on international trials.

“It raises some concerns,” O’Connor told Reuters Health. “If the patients have these differential treatment effects, we have to pay attention to it.”

There aren’t any clear-cut answers to why the outcomes vary by country.

It could be a question of different use of medications or devices to control heart failure, or it could be a chance finding because only one study included a large proportion of U.S. patients, the researchers write.