JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
VOL. 67, NO. 5, 2016
ª 2016 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
PUBLISHED BY ELSEVIER
ISSN 0735-1097/$36.00
http://dx.doi.org/10.1016/j.jacc.2015.12.006
EDITORIAL COMMENT
SPRINT
To Whom Do the Results Apply?*
Alan H. Gradman, MD
F
or the past several years, many physicians have
findings from 17,085 participants in the National
been puzzled by the rapidly changing recom-
Health and Nutrition Examination Survey to the U.S.
mendations for the treatment of hypertension.
population to estimate the number of individuals
The belief that “lower is better” has been challenged,
whose treatment would be altered if the SPRINT
and emphasis has been placed upon the risks accompa-
results were implemented. Of the 16.8 million people
nying excessive blood pressure (BP) reduction. In most
who meet the SPRINT inclusion criteria, antihyper-
recent guideline revisions, higher thresholds for initi-
tensive therapy would be initiated or intensified in
ating treatment and less aggressive BP targets have
6.6 million with SBP 130 to 139 mm Hg. Additionally,
been adopted for patients with diabetes or chronic kid-
the authors project that 25.5 million U.S. persons age
ney disease (CKD) and the elderly (1). These decisions
>50 years with SBP >120 mm Hg are at increased CV
were prompted by meta-analyses of clinical trials,
risk. They speculate that if a BP target <120 mm Hg
retrospective studies relating on-treatment BP to clin-
is accepted as the treatment standard, these in-
ical outcomes, and ACCORD (Action to Control Cardio-
dividuals might also be candidates for treatment.
vascular Risk in Diabetes), a prospective trial in
diabetic patients in which treatment to a systolic blood
pressure (SBP) target of <120 mm Hg was not found to
be superior to a higher target of <140 mm Hg (2,3).
SEE PAGE 463
The results of SPRINT imply that the threshold for
treatment should be reduced to 130 mm Hg and
With the publication of the SPRINT (Systolic Blood
target SBP to <120 mm Hg in a large segment of the
Pressure Intervention Trial), the tide has reversed (4).
population, including 35% of patients with treated
SPRINT was the largest trial ever conducted that was
hypertension and 19% of untreated patients with BP
specifically designed to evaluate BP targets. In
130 to 139 mm Hg. The latter group consists of pa-
SPRINT, 9,361 subjects who were >50 years of age,
tients with CKD (estimated glomerular filtration rate
had SBP >130 mm Hg, and had evidence of high car-
20 to 60 ml/min/1.73 m2), coronary artery disease
diovascular (CV) risk were randomized to target BPs
(CAD), a 10-year risk of CV disease >15% as esti-
of <140 or <120 mm Hg. The choice of drugs for in-
mated by the Framingham Risk Score, and all in-
dividual patients was not specified. Patients assigned
dividuals >75 years of age with SBP >130 mm Hg.
to the lower SBP target exhibited a 25% reduction in
Patients with diabetes are not affected as they were
the primary composite endpoint of major CV events
not studied in SPRINT.
and 23% lower mortality compared with those randomized to an SBP <140 mm Hg.
A key clinical question relates to management
of treated hypertensive patients with SBP 130 to
In this issue of the Journal, Bress et al. (5) explore the
139 mm Hg. Is it necessary to prescribe additional
practical implications of SPRINT. They extrapolated
medication to further reduce BP? Certainly, the results of SPRINT do not apply to patients with resistant
hypertension, usually defined as the need for >3
*Editorials published in the Journal of the American College of Cardiology
antihypertensive agents including a diuretic. Drug-
reflect the views of the authors and do not necessarily represent the
resistant patients were excluded from SPRINT by a
views of JACC or the American College of Cardiology.
From the Department of Medicine, Temple University School of
Medicine, Philadelphia, Pennsylvania. Dr. Gradman has reported that
screening algorithm that set an upper SBP limit for
each patient on the basis of the number of drugs
he has no relationships relevant to the contents of this paper to
taken at baseline. For easier-to-treat patients, there
disclose.
are also reasons to be cautious regarding treatment
474
Gradman
JACC VOL. 67, NO. 5, 2016
FEBRUARY 9, 2016:473–5
To Whom Do the Results Apply?
intensification. In most hypertension studies, on-
increased risk of stroke (e.g., Asians), adherence to the
treatment SBPs between 130 to 139 mm Hg are asso-
SPRINT SBP target of <120 mm Hg is recommended.
ciated with the lowest frequency of CV events (except
Several categories of untreated patients with SBP
stroke) compared with values above and below this
130 to 139 mm Hg included in SPRINT are also
range (6). In patients with hypertension and CAD, a
candidates for treatment. In patients with CKD, CAD,
J-shaped relationship has been observed with higher
left ventricular hypertrophy, and/or heart failure,
incidence of myocardial infarction seen at lower dia-
use of appropriate class(es) of antihypertensive
stolic BP. In several studies, the on-treatment SBP
agents is justified, if not always mandated, by previ-
associated with the lowest risk of CV endpoints was
ous studies. The results of SPRINT reinforce evidence
>140 mm Hg (7).
documenting the favorable effects of neurohormonal
The results of SPRINT are those of a single study
antagonists and other agents in the therapy of these
conducted in a unique population that excluded
conditions. Treatment should be instituted in accor-
subjects with diabetes, cerebrovascular disease, and
dance with the SPRINT protocol.
drug-resistant hypertension. It included a high pro-
There is little evidence, however, to support
portion of patients with mild CKD and many elderly
routine antihypertensive therapy in adults $75 years
people with well-controlled hypertension. It enrolled
of age with SBP >130 mm Hg. Placebo-controlled tri-
untreated individuals not classified as hypertensive
als on which the treatment of hypertension in the
by conventional criteria. Unlike patients cared for by
elderly are based enrolled only subjects with baseline
most cardiologists, a relatively small proportion
SBP $160 mm Hg (9). Although risk reduction in
(16.7%) had established CV disease. The differing re-
SPRINT for subjects $75 years of age was substantial
sults of SPRINT and ACCORD, 2 studies of similar
(33%), the number of untreated patients must have
design conducted by the same research group evalu-
been small, as 92% of participants were receiving
ating the same BP targets, are likely due to the
antihypertensive drugs at baseline. Although the
composition of the 2 patient populations. Although
SPRINT results are consistent with the possibility of
the SPRINT results are likely valid for the study as a
significant benefit, they must be considered pre-
whole, its therapeutic implications cannot be auto-
liminary and insufficient to mandate universal drug
matically applied to every patient who met the in-
therapy. Treatment is definitely an acceptable option
clusion criteria. A patient may belong to a subgroup
given the safety and tolerability of available drugs.
(e.g., patients with CAD) that made a very small
Additional clinical trials specifically designed to
statistical contribution to the overall results. It is
evaluate the effects of BP reduction in older subjects
possible that a study conducted exclusively in that
with untreated SBP 130 to 160 mm Hg constitute an
subgroup would yield very different results.
important public health priority.
It is important to recognize that the choice of SBP
Because of the small number of untreated patients
target as <120 mm Hg in SPRINT was arbitrary. It is
studied, the results of SPRINT are also insufficient to
unfortunate that the JNC-7 (Seventh Joint National
mandate drug treatment for patients with SBP 130 to
Committee) target of <130/80 mm Hg, widely recom-
139 mm Hg and a high Framingham risk score. The re-
mended for high-risk patients prior to ACCORD, has
sults of TROPHY (Trial of Preventing Hypertension)
never been properly evaluated in clinical trials. In a
and 1 other study indicate that renin-angiotensin-
perspective regarding the SPRINT trial, JNC-7 Chair,
aldosterone system inhibitors delay progression to
Dr.
target
hypertension (BP $140/90 mm Hg) when BP is in this
of <130/80 mm Hg “for most patients who are over
range, although the studies were not statistically
50 years of age and do not have diabetes” (8). This
powered to evaluate endpoint reduction (10). Many
makes sense, because at 3.26 years of follow-up in the
physicians treat BP 130 to 139 mm Hg in high-risk in-
SPRINT trial, the mean SBP was 121.5 mm Hg in the
dividuals on the basis of epidemiological evidence of
intensive-treatment group and 134.6 in the standard-
increased risk. The SPRINT findings are consistent
treatment group. In view of residual uncertainty
with this practice, and treatment is a reasonable op-
regarding optimal BP targets in many subgroups, it is
tion. There is presently no justification for extending
not prudent to radically alter treatment in patients
the findings of SPRINT to encompass the >25 million
Chobanian,
recommended
the
JNC-7
who have achieved SBP levels considered optimal on
Americans >50 years of age with SBP >120 mm Hg and
the basis of prior evidence. I favor the addition of 1
increased CV risk.
(only) additional agent from a different pharmacologic
class without further pursuit of SBP <120 mm Hg. In the
REPRINT REQUESTS AND CORRESPONDENCE: Dr.
event of treatment-emergent side-effects, the previ-
Alan H. Gradman, 1239 Shady Avenue, Pittsburgh,
ous regimen should be reinstituted. For patients at
Pennsylvania 15232. E-mail: [email protected].
Gradman
JACC VOL. 67, NO. 5, 2016
FEBRUARY 9, 2016:473–5
To Whom Do the Results Apply?
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KEY WORDS control, hypertension, population
health, systolic blood pressure, treatment
475