John Mandrola, MD

Disclosures

November 09, 2015

SPRINT investigators announced the results of their landmark study today at the American Heart Association (AHA) 2015 Scientific Sessions.[1]

What follows is my framing of the study and then three thoughts about applying its results to the real world—where I work. Deborah Brauser, my colleague at theheart.org on Medscape, has detailed coverage here.

Let's begin with the obvious: high blood pressure is not a disease; it is a risk factor for future disease. Life, or shall we say, not dying, is also a risk factor for future cardiovascular events.

SPRINT is an impressive trial that delivered definitive results in a diverse group of patients, including the elderly, women, and African Americans. Although SPRINT was terminated early, which can introduce bias, the large number of primary end points (n=564) provides reassurance that the findings are valid.

In the study, 9361 patients were randomized to either intense blood-pressure control with the goal of 120 mm Hg or standard care with a goal of 140 mm Hg.

SPRINT was a positive trial. Both the primary outcome, which was a composite of MI, acute coronary syndrome (ACS), stroke, heart failure, or cardiovascular death, and overall death were reduced by significant margins.

I don't like to speak of benefits in relative terms. Let's look at the absolute numbers from tables 2 and 3 of the New England Journal of Medicine paper.

Primary end point: There were 243 (of 4678) primary outcome events in the intense-treatment arm vs 319 (of 4683) in the standard-treatment arm. Over the 3.2 years of the trial, intense BP control prevented 76 events; the difference was 1.62% overall. The number needed to treat (NNT) was 61. The percent same result was 98.4%.

Overall death: There were 155 deaths from any cause in the intense-treatment arm (of 4678) vs 210  in the standard-treatment arm (4683). The difference was 1.2% or an NNT of 83. The percent same result was 98.8%.

Death from CV causes: There were only 37 CV deaths in the intense treatment arm vs 65 in the standard arm. The difference was 0.6% or an NNT of 167.

There were no significant differences in rates of stroke, MI, or ACS. Benefit in the primary outcome was driven most by heart-failure events and CV death. (I wonder why stricter blood-pressure control did not reduce coronary or stroke events.)

Adverse events overall: There were 1793 (38%) serious adverse events in the intensive group and 1736 (37.1%) in the standard group. So, no difference overall.

Adverse-events specifics: Investigators reported more hypotension, syncope, electrolyte abnormalities, and acute kidney injury in the invasive group. Falls with injury were not increased, and orthostatic hypotension was less frequent in the intensive arm.

We can't interpret these findings without going back to the methods.

Inclusion criteria: SPRINT included patients older than the age of 50, with high blood pressure and increased cardiovascular risk, which was defined by one of the following: actual blood vessel disease, chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] 20 to <60), Framingham risk greater than 15%, or age >75.

Exclusion criteria: Patients with diabetes and prior stroke were excluded. Patients with 1-minute standing BP less than 110 were also excluded.

Three Thoughts on Clinical Interpretation

In the days and weeks to come, many smart people will contribute to the conversation. Here are three issues that I feel are important.

Role of lifestyle: I searched the PDF document of the paper for the word, "lifestyle." It showed up only once. That is remarkable for a landmark paper in hypertension research. The average body-mass index (BMI) of study patients was nearly 30.

I am not naive to the challenge of helping patients improve their lifestyle, but there is ample evidence supporting the use of diet, exercise, sleep therapy, and alcohol moderation as potent BP-lowering agents. SPRINT investigators understandably used drugs to get BP to certain levels. That does not mean we must assume medication is the only way to achieve ideal BP. Instead, I think it's safe and wise to counsel patients that they can reap of the benefits of intensive blood-pressure control without necessarily taking more drugs.

If doctors do not take a leadership role in using diet and exercise as medicine, who will?

Role of shared decisions: Alongside the SPRINT article, the journal offered two editorials and a case presentation in which two experts opined as to whether an elderly woman should have her BP left alone or treated more aggressively.[2-4]

In thousands of words, I found no mention of discussing the trade-offs of the two strategies with patients. That deficiency is remarkable—and I hope it's due to the excitement of a big trial.

I reached out to Dr Richard Lehman (Oxford University, UK), and he offered this wisdom: "With participants of mean age 65+, quality of remaining life becomes increasingly important. . . . It will take some time for this to sink in and be computable in decision aids for individuals. But that must always be our aim—to be able to clearly explain to patients the benefits and harms of any particular strategy we propose."

Dr Harlan Krumholz (Yale University) had similar thoughts. "There are trade-offs that mean that we need to help people decide whether this option is best for them. The good news is that it is a terrific study and opens a new treatment option. It will not be easy to implement, as there is a lot of patient education involved in helping people make the right choice."

It's 2015; we are long past the era where doctors simply prescribe what they feel is best for people. When it comes to treating risk factors, not diseases, people are the experts in what is best for them. Some older patients may be willing to accept the risk of more aggressive treatment to get the benefits. Others, when told of the absolute benefits and risks, may not want the extra burden of therapy.

Role of patient selection: Although there are millions of people with high blood pressure, the SPRINT trial had specific entry and exclusion criteria. We must be careful extrapolating these results to patients. SPRINT-trial benefits apply to SPRINT-like patients.

Krumholz told me "we need more information about who stands to benefit most—and who least. [SPRINT] should not lead to lower targets being imposed on everyone."

Lehman agreed: "On the face of it, this seems like a really well-conducted trial, and it is astonishing to see such effect sizes over such a short time. Okay, the NNTs are still high, but actually BP treatment is lifelong, and so the extrapolated benefit could be much larger. In one way this is not good news, because I think the main effort of 'hypertension' research should be to get treatment better targeted at those who are most likely to benefit from it."

Please consider writing your thoughts in the comments section. This is an exciting time. There is a lot about SPRINT to digest. Conversation and thoughtful discourse will help us best apply this new knowledge to patient care.

JMM

Editor's note: An earlier version of this column incorrectly stated that orthostatic hypotension was more frequent in the intensive arm. It was less frequent.

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