This article is a collaboration between ڴŮ and:
The cardiovascular event and mortality reductions announced from the SPRINT Outcomes trial in topline results last week focused attention on blood pressure targets for the majority of hypertensive Americans but timing is now the question.
American Heart Association (AHA) president called the findings a for the organization's blood pressure targets for older adults compared with the relaxed standards suggested in 2013 by some members of a group originally set to update the JNC7 guidelines.
The AHA said it will include the findings in its guideline update already underway but noted that publication, expected in the next several months, will be necessary first. Many experts have also called for caution pending further details on safety.
For a veteran perspective on how SPRINT should play out in practice and guidelines -- and when -- ڴŮ spoke with , of the University of Alabama at Birmingham.
Oparil was principal investigator of one of the five clinical networks involved in SPRINT. She also served on writing committees for both the report supporting higher targets and a subsequent AHA/ACC statement re-emphasizing the sub-140 mm Hg target in coronary artery disease.
What follows is a lightly-edited version of that conversation.
ڴŮ: Could the SPRINT data be sufficient to unify professional society guidelines on blood pressure managment targets?
Oparil: "That is speculation, of course, because guidelines are supposed to take into account all the evidence that's available. This study only included people with hypertension over age 50 and who did not have diabetes, did not have a stroke previously, and did not have polycystic kidney disease. However, I think, because the results have been so outstandingly positive with respect to preventing cardiovascular disease outcomes and death, that yes, I think the study will influence practice broadly in the general population of hypertensive people."
MPT: When announcing the top-line results, you and other trial leaders cautioned that the SPRINT strategy should not be implemented in practice yet. It sets up a contradictory situation where you're widely publicizing the results but telling no one to act on it yet. How would you explain to clinicians why you set up this conflict for them?
Oparil: "I agree with you, you're asking me to explain a very confusing situation. The study has found that in the study population, which is fairly generalizable to most hypertensive persons in the United States, if you don't have diabetes and you're not real young, that getting the blood pressure to 120 produces a much greater effect in preventing cardiovascular events and preventing death than using the usual 140 goal. Now I think it's fair to say that's generalizable to the general population. I'm seeing patients in my own clinic tomorrow, which is not a SPRINT clinic, it's a regular clinic, and I will think harder about pushing the blood pressure lower in the older people. [Age] 50 to 65 isn't elderly in my book. But I think it does create a little bit of a problem for clinicians.
"We have to remember that in a randomized controlled trial, the clinic blood pressures are pretty accurate in the sense that these people are coming back visit after visit after visit, they're seen by the same coordinators who are very nice to them and don't upset them or anything, they have their blood pressure measured with an automated device according to AHA and international guidelines -- sitting quietly with your feet on the floor for 5 minutes, no smoking, no drinking coffee, no talking, no disturbance in the room. So those clinic blood pressures that we're seeing in SPRINT approach what ambulatory blood pressure or home blood pressure would be. If you're in a rushed clinic and you have inexperienced staff, you may be getting very high blood pressures, [artificially] high blood pressures, the white coat effect may be exaggerated. So if you try to push those clinic pressures down to 120, you may get into trouble. That's why you clinicians out there are as highly educated as you are and you use clinical judgment.
"The other mandate from the trial is that if it takes more than three or four drugs to get the blood pressure to 120, maybe you should think twice about pushing. There will be a lot of debate and a lot of discussion about that in the future and we're not trying to tell you we have the perfect answer for every patient and every provider."
MPT: The initial top-line announcement of the trial results was criticized for conveying relative but not absolute risk reductions. In retrospect, was that a mistake?
Oparil: "No, I don't think it was a mistake. It's not possible to analyze all the complicated data very, very quickly. The Data and Safety Monitoring Board, which is independent, advised the institute [NIH] -- , [MD,] the National Heart, Lung, and Blood Institute director -- that there was tremendous benefit in this study with respect to preventing cardiovascular disease events and death. The evidence of harm and the details on harm are really not available yet -- they're currently under analysis -- [but] were much less, so they recommended that the blood pressure intervention part of the trial be stopped. The trial goes on because people are being followed for various endpoints, like kidney endpoints. We don't know whether getting the blood pressure very low, to 120, might have some adverse effect on kidney function, and if so to what extent. Similarly, we don't know -- because nobody has ever studied this carefully -- whether getting the blood pressure very low will slow the decline of cognitive function or maintain normal decline of cognitive function or even delay the development of cognitive dysfunction. We are studying that by measuring cognitive function very carefully with questionnaires and detailed testing. The takes about an hour for each participant. A subcategory of patients get this detailed MIND test. And a subcategory of the subcategory gets an MRI, which measures both blood flow and the amount of brain that's there."
MPT: But in terms of not being able to analyze that quickly, in order to report a relative reduction you must know the absolute rate of events, at least for the primary endpoint. What's the rationale for not giving the actual rate?
Oparil: "Two things. We wanted to have as many endpoints available as possible up until August 20th, when the event recording or capture was supposed to stop. There hasn't been time for a thorough analysis of that. And the thought was that based on preliminary evidence based on the analyses by the statisticians the investigators in the trial say 'blah, public, this is the way it is,' reviewers of the manuscript once it's published question that and further analyses contradict that, that would create tremendous confusion. Dr. Gibbons was calling the shots here. We didn't have a decision-making role. [He] didn't want to jump the gun and make absolute pronouncements about what these rates are and the number needed to treat and so on. The real leaders up in Bethesda felt it was premature to do that. There is no effort to hide anything."
From the American Heart Association: