According to a recent news report a group of prominent heart failure doctors have eagerly embraced a lower blood pressure target of 120 mm Hg for heart failure patients based on the preliminary results of the SPRINT trial announced last month. But another equally prominent heart failure doctor says that it is far too early to apply the trial without seeing the full results. Just as important, he said, is the fact that the hypertension trial did not study heart failure patients, so any application of SPRINT to the heart failure population will be difficult at best.
SPRINT, you may recall, was the subject of a NIH press conference on September 11, during which it was announced that the trial had been stopped early after significant reductions in cardiovascular events and mortality had occurred in the group of hypertensive patients randomized to a blood pressure target of 120 mm Hg instead of the current 140 mm Hg. The full results of the trial will be presented for the first time at the American Heart Association meeting in November.
But the fact that almost no one has seen the full results hasn’t stopped many cardiologists and other experts from embracing the result. Most recently, at least three well-known heart failure experts publicly expressed support for the 120 mm Hg target for heart failure patients. The three– Margaret Redfield (Mayo Clinic), Ileaña Pina (Einstein College), and Clyde Yancy (Northwestern University)– spoke at the recent Heart Failure Society of American meeting, according to an article by Mitchell Zoler in Cardiology News.
“I think people were ready to do a reverse and accept a new, lower target,” the article quotes Redfield as saying. “We don’t have the [SPRINT] data yet, but it’s very unusual for the NHLBI to release trial information ahead of time, so it must be very dramatic.”
“The data and safety monitoring board had strict rules to govern early stopping,” said Yancy, who was himself a member of the SPRINT data and safety monitoring panel.
“I love the 120s; a 140-mm Hg target has always been too high for me,” said Piña.
When asked to comment Redfield and Piña stood by their comments, but asked for a clarification to state that their statements were provisional until they were able to see the full data.
But Milton Packer (University of Texas Southwestern Medical Center) said that he was tremendously surprised by these responses. “First,” he said, “we’ve learned over the years that it really would be important to see data before formulating an opinion.”
“Second,” said Packer, with a touch of sarcasm in his voice, “as far as I know SPRINT was not a heart failure trial.” SPRINT tested blood pressure targets in patients with hypertension. The trial “did not study different levels of blood pressure in patients with heart failure,” said Packer.
Packer said that “we actually have data from heart failure trials showing that drugs that lower blood pressure do not necessarily reduce mortality.” He cited studies with the blood-pressure lowering drugs prazosin and flosequinan; both lowered blood pressure, but prazosin did not reduce mortality and flosequinan had an adverse effect on survival. He also said that not all heart failure is alike. HFpEF (heart failure with preserved ejection fraction) is, in his view, a hypertensive disease, “so it may be reasonable to lower blood pressure to a target of 120 mm Hg in these patients. But for heart failure with reduced ejection fraction “we do not have any evidence for a blood pressure target. In fact, we have evidence that we should not be using blood pressure targets.”
Packer added: “I think we should hold the NIH to the same standards that we hold industry trials,” he said. “Would anyone recommend a major change in treatment without seeing the data just because a DSMB decided to stop a trial? Would anyone extrapolate the results to patients who were not even studied in the trial? I think we know better than that.”
Although the Cardiology News story clearly states that the opinions quoted in the story related to heart failure patients, it is possible that there may be some confusion in this regard. Asked to respond to how or whether SPRINT applies to heart failure patients, Clyde Yancy sent the following remarks:
We must be very clear on the question of BP targets in HF. For ambulatory heart failure with reduced ejection fraction we have no definitive data from trials or observational that an ideal target exists. Certainly avoiding hypotension is a pre-requisite for most studies (e.g., PARADIGM-HF) but identifying the ideal blood pressure in heart failure has been elusive. It is intuitive that an adequate blood pressure corresponds with a good prognosis but what defines adequate? And no study to date has treated patients to a goal blood pressure reduction.
In the acute decompensated HF space this question is addressed differently. A brilliant paper by Mihai Gheorghiade in JAMA several years ago defined with clarity that hypotension upon admission was associated with a striking increase in in-hospital mortality. That “cutpoint” was not at 90 mmHg (the conventional definition of hypotension) but at 110 mmHg.
In HFpEF, hypertension is oftentimes the most important co-morbidity and blood pressure reduction, (perhaps to the levels seen in SPRINT), is the goal but again, we don’t have agreed upon targets.
So the short version is this: to the best of my awareness, a target BP that defines best outcomes in ambulatory chronic heart failure has not been identified.