AHA: SPRINT Results Confirm Lower is Best BP Strategy

ORLANDO -- Lowering systolic blood pressure to a goal of 120 mm Hg in patients at high risk of cardiovascular events reduced the risk of heart attack, stroke, or death by 25% in the randomized SPRINT trial compared with the conventional target of 140 mm Hg, a robust benefit that many believe provides a convincing "lower is better" argument.

Over 3.26 years there were 243 deaths, heart attacks or strokes in the intensive treatment group for an event rate of 1.65% per year versus 319 events -- 2.19% per year -- in the control group, said Jackson T. Wright, MD, PhD, of University Hospitals, Case Western Reserve University in Cleveland, in an interview. Wright was lead investigator of the study.

Marc A. Pfeffer MD, PhD, of Harvard Medical School, who served as the discussant for SPRINT, called the study "a triumph" and noted that it represents the latest in a long series of studies have consistently found that high blood pressure is “bad” and lower BPs are better.

But Pfeffer said that getting BPs lower is not a job for the faint-hearted. "Don't expect your patients to say 'Thank you' when you tell them they need to take another pill."

Paul K. Whelton, MB, MD, PhD, of Tulane University in New Orleans, reported the much-awaited results from SPRINT [Systolic Blood Pressure Intervention Trial] at a late-breaking clinical trials session at the American Heart Association's Scientific Sessions here.

The trial recruited 9,361 people age 50 or older who had a baseline systolic pressure of 130 mm Hg or higher and randomly assigned them to an intensive intervention with a systolic goal of 120 mm Hg or to standard treatment with a systolic target of less than 140 mm Hg. After 3.26 years, the mean systolic pressure was 121.4 mm Hg in the intensive group versus 136.2 mm Hg in controls.

The study population was designed to be diverse: about a third were women, 30% African American, 28% older than 75.

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With intensive treatment the hazard ratio for the primary composite endpoint (MI, acute coronary syndromes, stroke, heart failure, or cardiovascular death) was 0.75 (95% CI 0.64-0.89, P<0.001). The number needed to treat to prevent a composite endpoint event was 61, while the NNT to prevent death from any cause was 90. Treating 172 people to a systolic target of 120 mm Hg prevented one cardiovascular death.

Whelton repeatedly pointed out that the SPRINT investigators achieved results "with ordinary, available drugs."

A major driver of the benefit, Whelton said, was a decrease in heart failure.

But the benefit came at a cost: 220 patients in the intensive treatment group had serious adverse events that were considered treatment related versus 118 patients in the control group (P<0.001).

Of note, the risk for adverse events did not differ significantly for those 75 or older, which had been a concern, Wright said, since many clinicians believe that lower targets present significant risk to the elderly. "That was not seen at all."

Wright said that it required an average of 2.8 drugs to achieve the lower target versus 1.8 drugs in the standard treatment group. The study protocol did not mandate specific drugs and all classes of antihypertensives were included in the formulary. (Takeda Pharmaceuticals International and Arbor Pharmaceuticals donated azilsartan as a single-agent pill and combined with chlorthalidone.)

Among the limitations of the SPRINT trial is the study population, which excluded persons with diabetes nor did it include "the most severe hypertensives," Wright said.

With the SPRINT results in hand, many cardiologists are openly calling for an overhaul of guidelines which have been in dispute for the last few years, especially after members appointed to the Eighth Joint National Committee (JNC8) published an "evidence-based guideline" recommending a systolic target of less than 150 mm Hg for elderly patients. The National Heart, Lung, and Blood Institute pointedly did not endorse that recommendation, nor has the AHA or American College of Cardiology.

James Stein, MD, of the University of Wisconsin School of Medicine in Madison, is one of the cardiologists who believe that it is now time to address the guideline controversy. The "results of SPRINT, along with last week's meta-analysis and persistent controversy surrounding the last HTN guidelines, now solidify the need for a HTN guideline re-do. The previous focus on higher targets was misguided and based on an overly narrow interpretation of the data," he wrote in an email.

But an even bigger challenge than getting guidelines updated will be implementation of lower targets in clinical practice, Stein wrote.

"How can we reproduce these highly favorable results in our practices in real patients who differ from trial participants and the setting of a clinical trial in meaningful ways? Key aspects will be patient selection (age over 50, higher CVD risk, BP >130 mm Hg), initial drug choice (usually combo therapy), and careful titration (monthly follow-up) as in SPRINT," he wrote.

Raymond Gibbons, MD, of the Mayo Clinic, in Rochester, Minn., said implementation will be a "system problem." Gibbons, who is a former president of the AHA, said that some health systems are already achieved remarkable rates of blood pressure control by implementing system-wide approaches.

For example, he said, Kaiser Permanente of Northern California increased compliance by switching to a mail order pharmacy. "Simply mailing the drugs rather than having the patient pick them up at the Kaiser pharmacy improved compliance," Gibbons said.

Although the results of the SPRINT study were officially released here and simultaneously published online in The Ne w England Journal of Medicine, the apparent benefit of targeting systolic pressures was trumpeted 2 months ago by the NHLBI when it halted the trial and released topline results.

But even with a notable lack of suspense about the results, the study is the centerpiece of the meeting, a standing confirmed by the decision to present the SPRINT findings in a separate standalone plenary session rather than the 10- to 15-minute time slots typically allotted to late-breaking studies -- treatment that Gibbons said was unprecedented.

Moreover, there are 11 SPRINT-associated papers being simultaneously published -- the study and six editorials or commentaries in NEJM, four perspectives in Hypertension, and a related paper in the Journal of the American College of Cardiology.

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