Improved stroke treatment a problem for drug trials

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Primary and recurrent stroke rates are falling, which is unarguably a positive trend. The declining numbers do complicate stroke research, however, because they mean studies must be larger, more expensive and more time-consuming.

A new analysis, published online May 2nd in Circulation, shows the average number of subjects in stroke recurrence studies has grown exponentially in the past 50 years, from a few hundred people in the 1960s to tens of thousands more recently.

Much of the increase stems from the fact that earlier studies were simply too small. "The studies from the '60s and '70s were woefully underpowered," Dr. Jeffrey Saver, director of the University of California, Los Angeles Stroke Center and the lead author of the new study, told Reuters Health.

But Dr. Saver and his colleagues found that declines in stroke recurrence also played a role. The mean annual recurrence rate dropped from 8.7% in the 1960s to 5.4% in the 1980s. By the 1990s, that figure had dropped by another 25%. The researchers calculated that stroke recurrence has been falling by about 1% each decade over the last 50 years.

"With each decline, we're needing to do larger and larger trials," said Dr. Saver. "It's very costly, and when a trial goes on for so long, there's a chance the results will no longer be relevant by the time the study is finished."

The phenomenon may also be negatively affecting trial results. The standard treatment outcome for stroke recurrence studies is reducing recurrence risk by at least 20%. If that risk is already declining independently, it becomes more difficult to achieve that outcome even with increases in the number of study participants.

"When a new drug comes along, it has to compete against that background effect," said Dr. Ralph Sacco, a stroke specialist at the University of Miami and the president of the American Heart Association.

Several recent stroke trials have failed in part because the researchers' predictions of what the recurrence rates would be were too high, Dr. Saver said.

Making matters more complicated, the decline in stroke recurrence may not be completely linear. In fact, Dr. Saver's results suggest the annual rate actually rose slightly between the 1990s and the 2000s. The percentage of study participants with diabetes also increased during that time, and diabetes is known to increase stroke risk.

"It's impressive how much blood pressure control has improved in the US," said Dr. Brent Egan, a stroke and hypertension researcher at the Medical University of South Carolina in Charleston who was not involved with the new study. "But, in general, the population is getting older and heavier, so there are some competing factors," he told Reuters Health.

Clearly, stroke studies are still needed, which means researchers will need to figure out ways to keep clinical trials from becoming unwieldy. One solution, said Dr. Sacco, may be to change the way treatments are evaluated - focusing, for instance, on quality of life measures instead of event-related outcomes such as mortality or stroke recurrence.

"More people are going to have strokes in the future, and there is still a lot of room for improvement in terms of treatment," he said.