It’s not often that a major clinical trial is stopped early because its preliminary results are so significant that the study’s investigators believe continuing the trial — and not letting everyone in the study benefit from the knowledge of those initial results — would be unethical.
But that’s what happened last Friday when federal health officials announced that the Systolic Blood Pressure Intervention Trial (SPRINT) was being ended a year early. The study had found, said the officials, that getting people to lower their systolic blood pressure to a more stringent target (120 mm Hg or lower) than the standard existing one (140 mm Hg or lower) could save lives.
Specifically, the study found that when people aged 50 or older with high blood pressure reached and maintained the lower rather than the existing blood pressure target, their relative risk of experiencing a cardiovascular “event” such as a heart attack or stroke fell by almost a third and their risk of dying prematurely from all causes fell by almost a quarter.
To reach that lower goal of 120 mm Hg, participants in the study took an average of three medications. Those in the standard group took an average of two medications.
Not yet published
“This study provides potentially lifesaving information,” said Dr. Gary Gibbons, director of the study’s primary sponsor, the National Heart, Lung, and Blood Institute (NHLBI), in a statement released to the press.
The key to that statement is “potentially.” For although these findings may very well prove to be an “important milestone” (as Gibbons also said) in our understanding and treatment of high blood pressure, we first need some more data — published data.
“This spring to the victory podium may have been premature,” he noted. “The judges — peer reviewers, editors, guideline authors, and other outside experts — haven’t had a chance to scrutinize the race.”
“It’s quite possible that SPRINT will eventually be viewed as a major, game-changing trial,” he stressed. “But there’s no way to know for sure until we see the full results.”
Here are just a few of the questions that Husten — and others — say need to be answered “before we can declare with confidence that the study delivers ‘potentially lifesaving information.’”
It was completely inappropriate to release the relative risk reductions without giving some idea of the absolute reduction in risk. It is simply impossible to assess the clinical significance of the trial finding without understanding this part of the story. [Here’s why.] (And let’s be honest: reporting relative risk reductions and not absolute risk reductions is one of the most common ways to hype a result.) …
We don’t know anything about the safety of the more aggressive regimen. This is a big concern because in recent years there’s been increasing awareness that many elderly people are suffering catastrophic falls when their blood pressure falls too low or too fast. …
We don’t know whether the lower target was effective in different subgroups. We do know that the SPRINT trial enrolled a high risk group of patients, but we don’t know yet, and it will take a lot of analysis to figure out, whether the results apply to a more general population, especially since there have been earlier trials in different populations that did not achieve the same result as SPRINT. …
‘The subject of enormous controversy’
“I think the NHLBI officials and investigators themselves gave the best reason why they should not have released the relative risk reductions: during the press conference they repeatedly stated that any concrete action based on the trial’s findings needed to await peer-reviewed publication,” Husten wrote. “I think it’s irresponsible for the NHLBI to say they have ‘potentially lifesaving information’ but then go on to say that no immediate changes are warranted until more complete results are available.”
There is “one point of comfort,” he pointed out. “We don’t need to worry too much at all about undue influence from the pharmaceutical industry. Nearly all the most common blood pressure drugs are now off patent.”
“But we do need to remember that blood pressure guidelines have been the subject of enormous controversy and contention in the last few years, and many of the SPRINT investigators have played an important role in these controversies,” Huston added. “And we do need to be concerned about the enormous tendency to turn otherwise healthy people into patients.”