intensive vs standard blood pressure control and cardiovascular disease outcomes in adults aged 75...

8/16/2019 Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged 75 Years

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Copyright 2016 American Medical Association. All rig hts reserved.

Intensive vs StandardBlood Pressure Control

andCardiovascular DiseaseOutcomes inAdultsAged≥75Years

A Randomized Clinical Trial

Jeff D.Williamson, MD, MHS; Mark A. Supiano,MD; William B. Applegate, MD, MPH; DanR. Berlowitz, MD;RuthC. Campbell,MD, MSPH;

GlennM. Chertow, MD;LarryJ. Fine,MD; William E. Haley, MD;Amret T. Hawfield,MD; Joachim H.Ix, MD, MAS; DalaneW. Kitzman,MD;

JohnB. Kostis, MD; MarieA. Krousel-Wood, MD; Lenore J. Launer,PhD; Suzanne Oparil, MD; Carlos J. Rodriguez, MD,MPH;

ChristianneL. Roumie, MD, MPH; Ronald I. Shorr, MD, MS; KayceeM. Sink, MD, MAS; Virginia G. Wadley, PhD; Paul K. Whelton, MD;

JeffreyWhittle,MD; NancyF. Woolard;JacksonT. Wright Jr, MD,PhD; Nicholas M. Pajewski, PhD;for the SPRINT ResearchGroup

IMPORTANCE The appropriate treatmenttarget for systolic blood pressure (SBP) in older

patients with hypertension remains uncertain.

OBJECTIVE To evaluate theeffects of intensive(


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In theUnited States, %of persons older than yearshave

hypertension, for whomcardiovascular disease complica-

tions are a leading cause of disability, morbidity, and

mortality.- Current guidelines provide inconsistent recom-

mendationsregardingthe optimalsystolicblood pressure(SBP)

treatment target in geriatric populations. European guide-

line committees haverecommended treatment initiationonly

above mm Hg for persons aged years or older. A re-

cent US guideline, a report from the panel appointed to the

Eighth Joint National Committee, recommended a SBP treat-

ment target of mm Hg for adults aged years or older.

However, a report from a minority of the members argued to

retain the previously recommended SBP treatment goal of

mm Hg, highlighting the lack of consensus.

Whether treatment targets should consider factors such

as frailty or functional status is also unknown. Observational

studies have noted differential associations among elevated

blood pressure (BP) and cardiovascular disease, stroke, and

mortality risk when analyses are stratified according to mea-

sures of functional status.- A recent secondary analysis of

the SystolicHypertension in the Elderly Program showed that

the benefit of antihypertensive therapywas limited to partici-

pants without a self-reported physical ability limitation. In

contrast, analyses from the Hypertension in the Very Elderly

Trial (HYVET)showeda consistentbenefitwith antihyperten-

sive therapy on outcomes irrespective of frailty status.

The Systolic Blood Pressure Intervention Trial (SPRINT)

recently reported that participants assigned to an intensive

SBP treatment target of less than mm Hg vs the standard

SBPtreatment goal oflessthan mmHg had a % lowerrela-

tive risk of major cardiovascular events and death, and a %

lower relativerisk of deathfrom anycause.This trial wasspe-

cifically funded to enhancerecruitmentof a prespecified sub-

group of adults aged yearsor older, and the study protocol

(appearsin Supplement ) alsoincludedmeasuresof functionalstatus andfrailty. Thisarticledetails results fortheprespecified

subgroupof adults aged years or older with hypertension.

Methods

Population

The design, eligibility, and baseline characteristics of SPRINT

have been described. The trial protocol was approved by

the institutional review board at each participating site.

Study participants signed written informed consent and were

required to be at increased risk for cardiovascular disease

(based on a history of clinical or subclinical cardiovasculardisease, chronic kidney disease [CKD], a -year Framingham

General cardiovascular disease risk ≥%, or age ≥ years). A

person was excluded if he or she had type diabetes, a his-

tory of stroke, symptomatic heart failure within the past

months or reduced left ventricular ejection fraction (%

of body weight) during the preceding months, an SBP of

less than mm Hg following minute of standing, or

resided in a nursing home.

StudyMeasurements

Sociodemographic data were collected at baseline, whereas

both clinicaland laboratory datawere obtained at baseline and

every months. Race and ethnicity information was ob-

tained via self-report. Blood pressure was determined using

themeanof properlysizedautomated cuff readings,taken

minuteapart after minutes of quiet rest without staffin the

room. Gait speed was measured via a timed -m walk per-

formed twice at the participant’s usual pace from a standing

start.The useof an assistive devicewas permittedif typically

used by the participant to walk short distances. The faster of

the gait speeds(measured in meters/second)was usedin the

analysis. Frailty status at randomizationwas quantified using

a previously reported -item frailty index.

Clinical Outcomes

A committee unaware of treatment assignment adjudicated

theprotocol-specifiedclinicaloutcomes.The primarycardiovas-

cular diseaseoutcome wasa compositeof nonfatal myocardial

infarction,acute coronary syndrome not resultingin a myocar-

dialinfarction,nonfatalstroke, nonfatal acutedecompensated

heartfailure,and death fromcardiovascularcauses. Secondary

outcomesincluded all-causemortalityand thecompositeof the

SPRINT primary outcome and all-cause mortality.

The primary renal disease outcome was assessed in par-

ticipants with CKD at baseline (estimated glomerular filtra-

tion rate [eGFR]


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assuming an event rate of .% peryear in thestandard treat-

ment group (Appendix B in Supplement ).

Linear-mixed modelswith anunstructuredcovariance ma-

trix, assuming independence across participants, were used

to model longitudinal differences in SBP between treatmentgroups. Fixed effects in the model were BP at randomization

and a treatmentgroupindicator. Thetime to first occurrence

of the primary composite outcome, all-cause mortality, pri-

mary composite outcome plus all-cause mortality, SAEs, and

loss to follow-upor withdrawing consent were compared be-

tween the randomized groups using Cox proportional haz-

ardsregressionmodels withthe baselinehazardfunctionstrati-

fied by clinic site (participants were recruited at clinics).

Follow-up time was censored on the date of last event ascer-

tainment on or beforeAugust , , thedateon which the

National Heart, Lung, and Blood Institute director decided to

stop the intervention.

Exploratory secondary analyses were conducted to exam-

inemodificationof thetreatmenteffect byfrailty statusand gait

speed. Neither frailty status nor gait speed was a prespecifiedsubgroup in the trial protocol. We fit separate Cox regression

models forfrailtystatusclassifiedas fit(frailtyindex≤.),less

fit(frailtyindex>. to≤.), or frail (frailty index >.),,

andforgait speedclassified as.m/sor greater (normal walker),

less than . m/s (slow walker), or missing. Interactions be-

tween treatmentgroup, frailty status, and gait speed were for-

mallytestedby includinginteractionterms withina Coxregres-

sion model (ie, using likelihood ratio tests to compare with a

model thatdid not allow the treatment effect to vary byfrailty

status or gait speed). For the primary cardiovascular disease

Figure 1. Eligibility,Randomization, andFollow-up forSystolic Blood Pressure(SBP) InterventionTrial(SPRINT)

ParticipantsAged75 Yearsor Older

14692 Assessed for eligibility

3756 Aged ≥75 y

9361 Randomized

2636 Aged ≥75 y

1317 Participants aged ≥75 y includedin primary analysis

66 Did not complete gait speedassessment at baseline

7 Frailty index could not becomputed at baseline

1319 Participants aged ≥75 y includedin primary analysis

57 Did not complete gait speedassessment at baseline

9 Frailty index could not becomputed at baseline

4678 Randomized to an SBP treatmenttarget


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compositeoutcome,sensitivityanalysesaccountingfor thecom-

peting riskof death were conducted using the subdistribution

hazard model of Fine and Gray. All hypothesis tests were

-sided at the % level of significance.

Additional analyses compared thetotalburden of SAEs be-

tweenthe randomized groups (allowing for recurrentevents)

using the mean cumulative count estimator (standard errors

computedusing bootstrapresampling).Hazard ratios (HRs)

were computed to compare therandomizedgroups usingthe

gap-time formation of thePrentice,Williams,and Peterson re-

current events regression model. All analyses were per-

formed using SASversion .(SAS Institute Inc) andthe R Sta-

tistical Computing Environment (http://www.r-project.org).

Results

BaselineCharacteristicsand StudyRetention

Participantsaged years or older wererandomizedto an SBP

target of less than mm Hg (intensive treatment group,

n = ) or an SBP target of less than mm Hg (standard

treatment group, n = ) (Figure ). The treatment groups

were similar for most characteristics with the exception of

frailty status and aspirin use (Table ). Overall, partici-

pants (.%) were classified as frail and (.%) as less

fit(Table ).A total of (.%) participants provided com-

plete follow-up data.

Table 1. BaselineCharacteristicsof ParticipantsAged 75YearsorOlder

Intensive Treatment(n = 1317)

Standard Treatment(n = 1319)

Female sex 499 (37.9) 501 (38.0)

Age, mean (SD), y 79.8 (3.9) 79.9 (4.1)

Race/ethnicity, No. (%)

White 977 (74.2) 987 (74.8)

Black 225 (17.1) 226 (17.1)

Hispanic 89 (6.8) 85 (6.4)

Other 26 (2.0) 21 (1.6)

Seated blood pressure, mean (SD), mm Hg

Systolic 141.6 (15.7) 141.6 (15.8)

Diastolic 71.5 (11.0) 70.9 (11.0)

Orthostatic hypotension, No. (%) 127 (9.6) 124 (9.4)

Serum creatinine, median (IQR), mg/dL 1.1 (0.9-1.3) 1.1 (0.9-1.3)

Estimated GFRa

Mean (SD), mL/min/1.73 m2 63.4 (18.2) 63.3 (18.3)

Level


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In the intensivetreatmentgroup, participants(.%)

wereclassified as frail compared with participants (.%)

in the standard treatment group. A total of participants

(.%) were classified as slow walkers (


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NNTBenefit of (NNTHarm of to to NNTBenefit of ).

In participants without CKD at the time of randomization,

more participants in the intensive treatment group com-

pared with the standard treatment group experienced the

secondary CKD outcome (a % decrease in eGFR from

baseline to an eGFR


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mentgroup vs .% in thestandardtreatmentgroup; HR,.

[% CI, .-.]); however, the absolute rate of ortho-static hypotension in combination with a report of dizziness

was higher but was not statistically significantly different in

the intensive treatment group (.% vs .% in the standard

treatment group; HR, . [% CI, .-.]). Even though

the SAErateswere higher with greater frailty or slowerwalk-

ing speed, these rates were not statistically differentby treat-

ment group when stratified by frailty status or gait speed.

Discussion

These results extend and detail the main SPRINT study find-

ings in community-dwelling persons aged years or older,demonstrating that a treatment goal for SBP of less than

mm Hg reduced incident cardiovascular disease by %

(from.% to.% peryear) andtotal mortality by% (from

.% to .%per year).Translatingthese findings intonum-

bers needed to treat suggests that a strategy of intensive BP

control for. years would be expected to prevent primary

outcome event for every persons treated and death from

any cause for every persons treated. These estimates are

lowerthanthose from theoverall results ofthe trialdue tothe

higher event rate in persons aged years or older. In addi-

tion,exploratory analysis suggested that the benefit of inten-

sive BP controlwas consistentamongpersons in thisage rangewho were frail or had reduced gait speed.

The overall SAE ratewas comparableby treatment group,

includingamongthe most frail participants.There were nodif-

ferences in the number of participants experiencing injuri-

ous fallsor in the prevalence of orthostatic hypotension mea-

sured at study visits. These results complement results from

other trials demonstrating improved BP control reduces risk

fororthostatic hypotension andhas no effecton risk forinju-

rious falls.- The numbers of participants aged years or

older whodroppedout of the study, were lost to follow-up, or

decided to discontinue the intervention but continued with

outcome assessment were low and did not differ by treat-

ment group.There areseverallimitations to these results fromSPRINT

involving participantsaged years or older. Eventhoughthe

trial wasdesigned toenhancerecruitmentof a prespecifiedsub-

group of adults aged years orolder, randomizationin SPRINT

wasnot stratified by categories of age. In addition, thetrial did

notenrollolderadults residing innursing homes,personswith

type diabetes or prevalent stroke (because of concurrent BP

lowering trials),, and individuals with symptomatic heart

failure dueto protocol differencesrequiredto maintainBP con-

trol in this condition. Therefore, the results reported in this

Table4. Incidence ofCardiovascular andMortalityOutcomes byFrailtyStatus andGaitSpeed

Intensive Treatment Standard Treatment

HR (95% CI)a P ValueP Value forInteraction

No./TotalWithOutcomeEvents

% (95% CI) WithOutcome Events/y

No./TotalWithOutcomeEvents

% (95% CI) WithOutcome Events/y

Frailty statusb

Primary outcomec

Fit 4/159 0.80 (0.30-2.12) 10/190 1.72 (0.93-3.20) 0.47 (0.13-1.39)d .20

.84Less f it 48/711 2.23 (1.68-2.97) 77/745 3.51 (2.81-4.39) 0.63 (0.43-0.91) .01

Frail 50/440 3.90 (2.96-5.15) 61/375 5.80 (4.52-7.46) 0.68 (0.45-1.01) .06

All-causemortality

Fit 5/159 0.98 (0.41-2.36) 6/190 1.01 (0.45-2.24) 0.95 (0.27-3.15)d .93

.52Less f it 26/711 1.16 (0.79-1.71) 52/745 2.24 (1.71-2.95) 0.48 (0.29-0.78) .003

Frail 40/440 2.95 (2.17-4.03) 49/375 4.28 (3.24-5.67) 0.64 (0.41-1.01) .05

Primary outcomeplus all-causemortalityc

Fit 8/159 1.59 (0.80-3.19) 13/190 2.24 (1.30-3.86) 0.71 (0.28-1.69)d .45

.88Less f it 65/711 3.01 (2.36-3.84) 108/745 4.90 (4.05-5.91) 0.60 (0.44-0.83) .002

Frail 69/440 5.37 (4.24-6.80) 84/375 7.95 (6.42-9.85) 0.67 (0.48-0.95) .02

Gait speed

Primary outcomec

Speed≥0.8m/s 59/880 2.22 (1.72-2.87) 86/893 3.24 (2.63-4.01) 0.67 (0.47-0.94) .02

.85Speed


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study amongpersons aged yearsor older do notprovide evi-

denceregarding treatment targets in these populations.Indi-

viduals with these conditions also representa subsetof older

persons at increased risk for falls.

No other chronicconditionswere excluded fromthis trial,

andthe frailty index applied in this study combined with the

assessment of gait speed contribute to assessing possible ef-

fectmodification by comorbidity andfunctional status.In ex-

ploratory analyses,there wasno evidenceof heterogeneity for

the cardiovascular benefit of intensive BP management by

frailty or gaitspeed. However, these analysesshould be inter-

preted cautiously. The analyses were not prespecified in the

trial protocoland werepossibly underpoweredbecauseSPRINT

was designed to consider only the ability to detect a treat-

menteffect in participants aged years or older as a whole.

Despite excluding somechronicconditions, .% of par-

ticipants aged years or older in this trial were categorized

as frail at baseline,and thedistribution of frailty statusparal-

lels that estimated for ambulatory, communityliving popula-

tions of similar age. In addition, theproportion of US adults

aged years or older who have hypertension and meet the

study entrycriteriahas beenestimated to represent %of that

population using the - National Health and Nutri-

tion Surveys(approximately . million individuals).There-

fore, participants aged years or older in this trial arerepre-

sentative of a sizeable fractionof adultsin this age groupwith

hypertension.

There are several important comparisons to make with

HYVET, which randomized patients aged years or

older withinEuropeand Asia (meanage, years[ yearsolder

thanSPRINT]; meanentry SBP, mm Hg[ mm Hghigher

thanSPRINT])to either therapywithindapamide, withor with-

out the angiotensin-converting enzyme inhibitor perindo-

pril, or placebo with an SBP treatment goal of less than

mm Hg. The -year between-group SBP difference was

mm Hg (the active treatment group achieved a mean SBP

of mm Hg, slightly higherthan the SPRINTbaselineSBP).

Similar to SPRINT, HYVETwas terminated early (ata median

follow-uptime of .years) dueto significantreductions in the

incidence rate of totalmortality. A retrospective analysis of the

HYVET population conducted to determine its frailty status

identified that() the cohort’s frailty statuswas similar to that

of community living populationsof similarageand ()the treat-

mentbenefitswere similar evenin themostfrail participants.

Taken together,currentresults fromSPRINTalso reinforce and

extend HYVET’s conclusions that risk reductions in cardio-

vascular disease events and mortality from high BP treat-

ment are evident regardless of frailty status.

Among all participantsaged years or older,the SAEsre-

lated to acute kidney injury occurred more frequently in the

intensive treatment group ( participants [.%] vs par-

ticipants[.%] in the standardtreatment group).The differ-

ences in adverse renal outcomes may be related to a revers-

ibleintrarenalhemodynamiceffect of the reduction in BP and

more frequent use of diuretics, angiotensin-converting en-

zymeinhibitors, andangiotensin II receptorblockersin thein-

tensivetreatment group.

,

Althoughthere isno evidenceof permanent kidney injury associated with the lower BP goal,

thepossibilityof long-term adverserenal outcomescannotbe

excluded and requires longer-term follow-up.

Considering the high prevalence of hypertension among

older persons, patients and their physicians may be inclined

to underestimate the burden of hypertension or the benefits

of lowering BP, resulting in undertreatment. On average, the

benefits that resulted from intensive therapy required treat-

ment with additional antihypertensive drug and additional

earlyvisits for dose titration and monitoring. Future analyses

Figure 2. Kaplan-MeierCurves for thePrimaryCardiovascular Disease

Outcome in Systolic BloodPressure Intervention Trial (SPRINT)

inParticipantsAged75 YearsorOlderby BaselineFrailty Status

0.4

0.3

0.2

0.1

0

0

190159

1

186151

2

182150

3

94107

4

1916

5

C u m u l a t i v e

H a z a r d

Fit (FI ≤0.10)

YearsNo. at risk

Type of treatmentStandardIntensive

HR, 0.47 (95% CI, 0.13-1.39);

Cox regression P =.20

Standard treatment

Intensive treatment

No. at riskType of treatment

StandardIntensive

Standard treatment

Intensive treatment

0.4

0.3

0.2

0.1

00

745711

1

697677

2

653644

3

390378

4

9193

5

C u m u l a t i v e

H a z a r d

Less fit (FI >0.10 to ≤0.21)

Years

HR, 0.63 (95% CI, 0.43-0.91);

Cox regression P =.01

No. at riskType of treatment

StandardIntensive

Standard treatment

Intensive treatment

0.4

0.3

0.2

0.1

00

375440

1

338398

2

305371

3

177223

4

4971

5

C u m u l a t i v e H a z a r d

Frail (FI >0.21)

Years

HR, 0.68 (95% CI, 0.45-1.01);Cox regression P

=.06

Tinted regions indicate 95% confidence intervals; FI, 37-itemfrailty index;

HR, hazardratio. Theprimary cardiovasculardisease outcome was a composite

of nonfatal myocardial infarction,acute coronary syndrome not resulting in a

myocardial infarction,nonfatal stroke, nonfatal acutedecompensatedheart

failure, and deathfrom cardiovascular causes.

Research Original Investigation IntensiveBloodPressureControl in AdultsAged75 Years or Older

E8 JAMA Publishedonline May 19,2016 (Reprinted) jama.com


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of SPRINT data may be helpful to better define the burden,

costs,and benefits of intensive BP control. However, thepre-

sentresults have substantial implications for the future of in-

tensive BP therapy in older adultsbecause of this condition’s

highprevalence,the highabsolute riskfor cardiovascular dis-

ease complications fromelevatedBP,and thedevastatingcon-

sequencesof such events onthe independentfunctionof older

people.,,,

Conclusions

Among ambulatory adults aged years or older, treating to

an SBP target of less than mm Hg compared with an SBP

target of less than mm Hg resulted in significantly lower

rates of fatal and nonfatal major cardiovascular events and

death from any cause.

ARTICLE INFORMATION

Published Online: May 19,2016.

doi:10.1001/jama.2016.7050 .

Author Affiliations: Section on Gerontology and

Geriatric Medicine,Wake Forest Schoolof Medicine,

Departmentof Internal Medicine, Winston-Salem,

NorthCarolina (Williamson,Applegate, Sink,

Woolard); Divisionof Geriatrics, School of Medicine,

Universityof Utah,Salt LakeCity (Supiano);

Veterans Affairs Salt LakeCity,GeriatricResearch,

Education, and Clinical Center,Salt LakeCity,Utah

(Supiano); Bedford VeteransAffairs Hospital,

Bedford, Massachusetts (Berlowitz);School of

PublicHealth, BostonUniversity,Boston,

Massachusetts (Berlowitz);Department of

Medicine,Medical Universityof SouthCarolina,

Charleston (Campbell);Department of Medicine,

Stanford UniversitySchool of Medicine,Palo Alto,

California (Chertow);Clinical Applicationsand

PreventionBranch, Division of Cardiovascular

Sciences, National Heart,Lung, and Blood Institute,

Bethesda, Maryland (Fine); Departmentof

Nephrology and Hypertension, MayoClinic,

Jacksonville, Florida(Haley);Section on

Nephrology, Wake Forest School of Medicine,

Winston-Salem,North Carolina (Hawfield);Division

of Nephrologyand Hypertension, Departmentof

Medicine,Universityof California, San Diego(Ix);

Divisionof PreventiveMedicine, Departmentof

Family Medicine and PublicHealth, Universityof

California, San Diego(Ix); Departmentof Medicine,

Nephrology Section, VeteransAffairs San Diego

Healthcare System, San Diego, California (Ix);

Section on CardiovascularMedicine, Wake Forest

Schoolof Medicine, Winston-Salem, NorthCarolina

(Kitzman);Cardiovascular Instituteat Rutgers

RobertWood Johnson Medical School,

New Brunswick,New Jersey (Kostis); Department

of Medicine,TulaneUniversitySchool of Medicine,

New Orleans, Louisiana (Krousel-Wood);

Departmentof Epidemiology, Tulane University

Schoolof PublicHealth and Tropical Medicine,

New Orleans, Louisiana (Krousel-Wood);Center for

AppliedHealth Research,Ochsner Clinic

Foundation,New Orleans, Louisiana

(Krousel-Wood);IntramuralResearchProgram,

National Instituteon Aging,Bethesda,Maryland

(Launer); Division of Cardiovascular Disease,

Departmentof Medicine,Universityof Alabama,

Birmingham(Oparil); Division of PublicHealth

Sciences, Departmentof Epidemiology and

Prevention, Wake Forest School of Medicine,

Winston-Salem,North Carolina (Rodriguez);

Veterans Health Administration-Tennessee Valley

Healthcare System Geriatric Research Education

Clinical Center,HSR&D Center,Nashville(Roumie);

Departmentof Medicine,Vanderbilt University,

Nashville,Tennessee (Roumie);Department of

Epidemiology, Universityof Florida, Gainesville

(Shorr); Geriatric Research,Education,and Clinical

Center,Malcom Randall VeteransAdministration

Medical Center,Gainesville, Florida(Shorr);

Departmentof Medicine,Universityof Alabama,

Birmingham(Wadley); Departmentof

Epidemiology, TulaneUniversitySchool of Public

Health and TropicalMedicine,New Orleans,

Louisiana (Whelton); Departmentof Medicine,

Medical Collegeof Wisconsin,Milwaukee (Whittle);

PrimaryCare Division, Clement J. Zablocki Veterans

Affairs Medical Center,Milwaukee, Wisconsin

(Whittle);Division of Nephrologyand

Hypertension, Departmentof Medicine,

Case WesternReserve University, Cleveland,Ohio

(Wright);Division of PublicHealth Sciences,

Departmentof Biostatistical Sciences, Wake Forest

School of Medicine,Winston-Salem, NorthCarolina(Pajewski).

Author Contributions: Dr Pajewskihad full access

toallof the datain the study and takes

responsibility forthe integrityof thedataand the

accuracy of thedataanalysis.

Study concept and design: Williamson,Supiano,

Applegate,Berlowitz,Chertow, Fine,Kitzman,

Launer,Rodriguez,Shorr,Sink, Wadley, Whelton,

Wright, Pajewski.

Acquisition, analysis, or interpretation of data:

Williamson, Supiano, Applegate,Berlowitz,

Campbell, Chertow,Fine, Haley, Hawfield, Ix, Kostis,

Krousel-Wood, Oparil, Rodriguez,Roumie, Shorr,

Sink,Whelton,Whittle, Woolard, Wright, Pajewski.

Drafting of the manuscript: Williamson,Supiano,

Applegate,Shorr,Wright, Pajewski.

Critical revision of the manuscriptfor important intellectual content: Williamson, Supiano,

Applegate,Berlowitz,Campbell, Chertow,Fine,

Haley, Hawfield, Ix, Kitzman, Kostis, Krousel-Wood,

Launer,Oparil, Rodriguez, Roumie, Sink,Wadley,

Whelton, Whittle,Woolard, Wright, Pajewski.

Statistical analysis: Pajewski.

Obtained funding: Williamson, Chertow,Fine,

Kitzman, Oparil,Wright.

Administrative, technical, or material support:

Williamson, Campbell, Ix, Kitzman, Kostis, Oparil,

Roumie, Whelton, Woolard, Wright.

Study supervision: Williamson, Applegate,

Berlowitz, Fine,Kitzman,Oparil, Wadley,Whelton,

Wright.

Conflict of Interest Disclosures: Theauthors have

completedand submittedtheICMJEFormfor

Disclosure of PotentialConflicts of Interest.Dr

Williamson reported receiving nonfinancialsupport

from TakedaPharmaceuticals and Arbor

Pharmaceuticals duringthe conduct of the study.

Dr Kitzman reported receiving personal fees from

Merck,Forest Labs,and Abbvie; personal fees and

other fromGilead andRelypsa;andgrants from

Novartis outsidethe submitted work.Dr Oparil

reported receiving personal fees from Forest

LaboratoriesInc; grants, personal fees,and

nonfinancialsupport from Medtronic;personal fees

fromAmgen (Onyxis subsidiary); grantsand

personal feesfrom AstraZeneca and Bayer

Healthcare Pharmaceuticals Inc;personal feesfrom

Boehringer-Ingelheim and GlaxoSmithKline; grants

fromMerck andCo; andservingas co-chair forthe

EighthJoint National Committee.No other

disclosures werereported.

Funding/Support: The SPRINTstudy wasfunded

by the National Institutesof Health (including the

National Heart,Lung, and Blood Institute,

the National Instituteof Diabetes and Digestiveand

KidneyDiseases,the National Instituteon Aging,

and theNational Instituteof Neurological

Disorders and Stroke) undercontracts

HHSN268200900040C, HHSN268200900046C,

HHSN268200900047C, HHSN268200900048C,

and HHSN268200900049Cand interagencyagreement A-HL-13-002-001. It was also supported

in part with resources and use of facilities through

the Department of Veterans Affairs. Azilsartan and

chlorthalidone (combined with azilsartan) were

provided by Takeda Pharmaceuticals International

Inc. Additional support was provided by grants

P30-AG21332 and R01-HL10741 from the Wake

Forest Claude Pepper Older Americans

Independence Center; through the following

National Center for Advancing Translational

Sciences clinical and translational science awards:

UL1TR000439 (awarded to Case Western Reserve

University); UL1RR025755 (Ohio State University);

UL1RR024134 and UL1TR000003 (University of

Pennsylvania); UL1RR025771 (Boston University);

UL1TR000093 (Stanford University);

UL1RR025752, UL1TR000073, and UL1TR001064(Tufts University); UL1TR000050 (University of

Illinois); UL1TR000005 (University of Pittsburgh);

9U54TR000017-06 (University of Texas

Southwestern Medical Center);

UL1TR000105-05 (University of

Utah); UL1 TR000445 (Vanderbilt University);

UL1TR000075 (George Washington

University); UL1 TR000002 (University of

California, Davis); UL1 TR000064 (University of

Florida); and UL1TR000433 (University of

Michigan); and by National Institute of General

Medical Sciences, Centers of Biomedical Research

Excellence award NIGMS P30GM103337 (awarded

to Tulane University).

Roleof the Funder/Sponsor:TheSPRINT steering

committee was responsiblefor thedesign and

conduct of the study, including thecollection and

managementof the data.Scientists at the National

Institutes of Healthas a group andthe principal

investigator of theVeterans Affairsclinical network

had1 vote on thesteering committeeof thetrial.

Therewere 7 votingmembersof thesteering

committee.The National Institutesof Health, the

US Department of VeteransAffairs,and theUS

government hadno rolein analysis and

interpretation of thedata; preparation,review, or

approval of themanuscript; anddecisionto submit

the manuscriptfor publication.

IntensiveBloodPressureControl in AdultsAged75 Years or Older Original Investigation Research

jama.com (Reprinted) JAMA Publishedonline May 19,2016 E9


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10/10


Group Information: Themembersof theSPRINT

Research Group havebeen published elsewhere.13

Disclaimer: Thecontent is solelythe responsibility

of theauthorsand does notnecessarilyrepresent

theofficialviewsof theNational Institutes of

Health, theUS Departmentof VeteransAffairs,or

the US government.

Previous Presentation: Presentedin partat the

Gerontological Society of America annualmeeting;

November 21, 2015;Orlando,Florida.

Additional Contributions: We thank Sarah

Hutchens andPamela Nance,BA (bothwith the

WakeForest Schoolof Medicine),for their

assistancein preparationof themanuscript,for

whichneitherreceived any compensation.

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Research Original Investigation IntensiveBloodPressureControl in AdultsAged75 Years or Older

E10 JAMA Publishedonline May 19,2016 (Reprinted) jama.com

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