success and predictors of blood pressure control in...

VOL. IV NO. VI NOVEMBER/DECEMBER 2002 THE JOURNAL OF CLINICAL HYPERTENSION 393

*For a complete list of members of the ALLHAT Collaborative Research Group see JAMA. 2000;283:1973–1975.

Context. Blood pressure control (<140/90 mmHg) rates for hypertension fall far short of the USnational goal of 50% or more. Achievable controlrates in varied practice settings and geographicregions and factors that predict improved bloodpressure control are not well identified.Objective. To determine the success and predic-tors of blood pressure control in a large hyperten-sion trial involving a multiethnic population indiverse practice settings.Design. The Antihypertensive and Lipid-LoweringTreatment to Prevent Heart Attack Trial is a ran-domized, double-blind, active-controlled clinical trialwith a mean follow-up of 4.9 years. Participantenrollment began in February 1994 and follow-upwas completed in March 2002.Setting. A total of 623 centers in the United States,Canada, and the Caribbean.Participants. A total of 33,357 participants (aged≥55 years) with hypertension and at least one othercoronary heart disease risk factor.

Interventions. Participants were randomly assignedto receive (double-blind) chlorthalidone, 12.5–25 mg/d(n=15,255), amlodipine 2.5–10 mg/d (n=9048), orlisinopril 10–40 mg/d (n=9054) after other med-ication was discontinued. Doses were increased with-in these ranges and additional drugs from other class-es were added as needed to achieve blood pressurecontrol (<140/90 mm Hg).Main Outcome Measures. The outcome measuresfor this report are systolic and diastolic bloodpressure, the proportion of participants achievingblood pressure control (<140/90 mm Hg), and thenumber of drugs required to achieve control in allthree groups combined.Results. Mean age was 67 years, 47% werewomen, 35% black, 36% diabetic; 90% were onantihypertensive drug treatment at entry. At thefirst of two pre-randomization visits, blood pres-sure was <140/90 mm Hg in only 27.4% of par-ticipants. After 5 years of follow-up, the percentcontrolled improved to 66%. Systolic blood pres-sure was <140 mm Hg in 67% of participants,diastolic blood pressure was <90 mm Hg in 92%,the mean number of drugs prescribed was2.0±1.0, and the percent on ≥2 drugs was 63%.Blood pressure control varied by geographicregions, practice settings, and demographic andclinical characteristics of participants.Conclusions. These data demonstrate that bloodpressure may be controlled in two thirds of a

O r i g i n a l P a p e r s

Success and Predictors of Blood PressureControl in Diverse North AmericanSettings: The Antihypertensive and Lipid-Lowering Treatment to PreventHeart Attack Trial (ALLHAT)

William C. Cushman, MD; Charles E. Ford, PhD; Jeffrey A. Cutler, MD; Karen L. Margolis, MD, MPH; Barry R. Davis, MD, PhD; Richard H. Grimm, MD, PhD; Henry R. Black, MD; Bruce P. Hamilton, MD;

Joanne Holland, MD; Chuke Nwachuku, MA, MPH; Vasilios Papademetriou, MD; Jeffrey Probstfield, MD;Jackson T. Wright, Jr., MD, PhD; Michael H. Alderman, MD; Robert J. Weiss, MD; Linda Piller, MD, MPH;

Judy Bettencourt, MPH; Sandra M. Walsh, MA, for the ALLHAT Collaborative Research Group*

Address for correspondence: William C. Cushman, MD, Chief, Preventive MedicineSection (111Q), Veterans Affairs Medical Center,Professor of Preventive Medicine and Medicine,University of Tennessee College of Medicine, 1030Jefferson Avenue, Memphis, TN 38104E-mail: [email protected] received October 17, 2002;accepted October 23, 2002

multiethnic hypertensive population in diversepractice settings. Systolic blood pressure is moredifficult to control than diastolic blood pressure,and at least two antihypertensive medications arerequired for most patients to achieve blood pres-sure control. It is likely that the majority of peo-ple with hypertension could achieve a blood pres-sure <140/90 mm Hg with the antihypertensivemedications available today. (J Clin Hypertens.2002;4:393–404) ©2002 Le Jacq Communications, Inc.

Since the 1990’s, blood pressure (BP) control in theUnited States has been defined as <140/90 mm

Hg. Based on this definition, the BP control rate wasfound to be 27%–29% in a representative sample ofthe noninstitutionalized adult US population in theNational Health and Nutrition Examination Surveyof 1988–1991 (NHANES III).1,2 Correspondingdata from other countries have shown even lowercontrol rates than those in the United States.3,4 Ameasure from NHANES III more comparable toAntihypertensive and Lipid-Lowering Treatment toPrevent Heart Attack Trial (ALLHAT) partici-pants—i.e., BP control among those treated—ranged generally from about 30%–45% in olderadults from various sex-race/ethnicity groups.1Control among treated patients was only 33%among persons 45 years and older in OlmsteadCounty, Minnesota5 and less than 25% in oldermostly white males at a group of New EnglandVeterans Affairs Medical Centers.6

These low BP control rates have been difficult toexplain, given the number of apparently well-tolerat-ed medications available for the management ofhypertension,2 extensive public health efforts to iden-tify and treat individuals with hypertension, and theperiodic publication of consensus guidelines, such asreports of the Joint National Committee onPrevention, Detection, Evaluation, and Treatment ofHypertension2,7 and the World Health Organization-International Society of Hypertension.8 Factors relat-ed to access to care, provider practice patterns, andpatient adherence have all been proposed as barriersto BP control. Several reports strongly suggest that amajor factor in inadequate BP control is the physi-cian’s failure to increase doses or numbers of antihy-pertensive medications when seeing a patient withuncontrolled BP.6,9

The Antihypertensive and Lipid-Lowering Treat-ment to Prevent Heart Attack Trial (ALLHAT) is alarge clinical trial conducted in the United States,Canada, and the Caribbean, and sponsored by theNational Heart, Lung, and Blood Institute of the US

National Institutes of Health. The primary objectiveof ALLHAT was to compare the coronary heart dis-ease (CHD) event rates in 42,418 participants ran-domly allocated to four antihypertensive agents: thediuretic chlorthalidone, the angiotensin-convertingenzyme (ACE) inhibitor lisinopril, the calcium chan-nel blocker amlodipine, and the alpha blocker dox-azosin. The BP goal for all groups was <140/90 mmHg. The doses of the blinded drugs could beincreased and additional open-label agents fromother classes of antihypertensive drugs could beadded and doses increased as needed to achieve thislevel of BP control. The purpose of this report is todescribe BP control in ALLHAT over time, its rela-tionship to the numbers and doses of drugs used,and the factors that predicted BP control in thislarge hypertensive population from diverse practiceand geographical settings. The doxazosin partici-pants are excluded from this report, since that armof the trial was stopped early due in part to excesscardiovascular event rates compared with chlor-thalidone.10 Those results suggested that alphablockers should not be used as initial therapy forhypertension; therefore BP control rates with a regi-men beginning with an alpha blocker were notincluded in the current analyses. Otherwise, the ran-domization arms of the trial are not distinguished inthis paper; BP control by treatment group will bepresented in subsequent reports.

METHODS The rationale and design of ALLHAT are present-ed in detail elsewhere.11,12 Briefly, eligible partici-pants for ALLHAT were men and women aged 55years or older who had systolic BP (SBP) of at least140 mm Hg and/or diastolic BP (DBP) of at least90 mm Hg, or took medication for hypertension,and had at least one additional risk factor forCHD. These risk factors included previous myo-cardial infarction or stroke (>6 months or age inde-terminate), other atherosclerotic vascular disease,ischemic changes on an electrocardiogram withinthe past 2 years, left ventricular hypertrophy byelectrocardiogram or echocardiogram, type 2 dia-betes, current cigarette smoking, and low high-density lipoprotein cholesterol level (<35 mg/dL).BP eligibility criteria were based on the partici-pant’s current antihypertensive treatment statusand on the average of two, seated BP measure-ments at each of two pre-randomization visits (vis-its 1 and 2). For untreated participants (and thosetreated for less than 2 months), BP inclusion crite-ria at both visits were average SBP ≥140 and/orDBP ≥90 mm Hg but BP ≤180/110 mm Hg. Treated

THE JOURNAL OF CLINICAL HYPERTENSION VOL. IV NO. VI NOVEMBER/DECEMBER 2002394

participants were required to have BP ≤160/100mm Hg at visit 1 and ≤180/110 mm Hg at visit 2.The higher reading at visit 2 allowed for with-drawal of antihypertensive medication between thetwo visits when necessary. Eligible participantswere randomized into the trial at visit 2, at whichtime all prior antihypertensive medications werediscontinued. Details of the inclusion and exclu-sion criteria have been described previously.11,13

From February 1994 to January 1998, 42,418 par-ticipants were recruited in 623 centers in theUnited States, Canada, Puerto Rico, and the USVirgin Islands.14,15 All participants signed an in-formed consent form, and all centers received insti-tutional review board approval.

Participants were assigned by a computer-generatedrandomization schedule to one of four treatments:chlorthalidone, amlodipine, lisinopril, or doxazosin, ina ratio of 1.7:1:1:1, respectively. Randomization wasstratified by center and blocked over time to maintainthe ratio. More participants were assigned to chlor-thalidone in accordance with Dunnett’s multiple com-parison procedure for comparing three treatmentgroups to a single control group.16 The randomizationcode was held only by the ALLHAT Clinical TrialsCenter (CTC). The treatment goal in each of the fourarms was a BP <140/90 mm Hg. (As noted above, thedoxazosin arm of the trial was terminated early andwill not be discussed hereafter.)

All three study drugs were encapsulated andidentical in appearance so the identity of eachagent was masked at each of three dosage levels:12.5, 12.5 (sham titration), and 25 mg/d forchlorthalidone; 2.5, 5, and 10 mg/d for amlodip-ine; and 10, 20, and 40 mg/d for lisinopril. If par-ticipants did not meet the BP goal while taking themaximum tolerated dosage of the initial blindedmedication, an open-label Step 2 agent (but not amedication from the same class as the study drugs)could be added and increased in three doses untilgoal was reached. The three Step 2 agents (anddoses) were atenolol (25–100 mg/d), reserpine(0.05–0.2 mg/d), and clonidine (0.1–0.3 mg twiceper day). If goal BP was still not achieved, an open-label Step 3 agent, hydralazine (25–100 mg twiceper day), could be added. After initial titration vis-its, participants were seen routinely every 3 monthsduring the first year of follow-up and every 4months thereafter for up to 8 years of follow-up.

Medication doses were increased or additionalmedications were added during follow-up if BPwas not at goal. Non-study open-label drugs couldalso be added to or substituted for Step 2 or 3open-label medications to improve tolerance or BP

control. However, use of open-label medicationsfrom one of the masked classes of drugs was to beavoided unless SBP was >160 mm Hg and/or DBPwas >100 mm Hg after maximum tolerated titrationof drugs from each of the three steps, or a compellingindication, such as heart failure, arose for one of themasked classes of drugs. A medication dose could bedecreased or a medication stopped if it was believedto be causing adverse effects.

Trained observers using standardized techniquesmeasured BPs during the trial. SBP was defined asthe first Korotkoff sound (1st phase), and the DBPas the reading at the last Korotkoff sound (5thphase). The measurements were taken only afterthe participant had been seated quietly for at least5 minutes, in a comfortable posture, with feet flaton the floor. The readings were taken in the sittingposition with the arm at or as close to the level ofthe heart as possible. The cuff was deflated at arate of 2 mm/sec until 10 mm Hg below the levelof the diastolic reading was reached. Two measure-ments were taken, with at least a 30-second inter-val between the measurements, and recorded to thenearest even number. All BP measurements werecalculated as the average of these two readings.

STATISTICAL METHODS The baseline characteristics of age, BP, heart rate,body mass index (BMI), serum creatinine, glucose,total cholesterol, low-density lipoprotein (LDL)and high-density lipoprotein (HDL) cholesterol,and triglycerides of participants in ALLHAT weretabulated for subgroups by race, sex, diagnoseddiabetes, age, smoking, diagnosed atheroscleroticcardiovascular disease (ASCVD), and obesity.Blood pressure, BP control (SBP/DBP <140/90 mmHg), use of additional (≥2, ≥3, and ≥4) drugs, andpercent remaining on Step 1 drugs at baseline andfollow-up were calculated. BP control and use ofadditional drugs were also tabulated for the afore-mentioned subgroups. Frequency distributions of SBP and DBP control were obtained. Logisticregression analyses were performed to assess theinfluence of independent baseline variables on eachof two outcomes at 36 months of follow-up: BPcontrol and use of two or more drugs. The inde-pendent baseline variables include participants’age, sex, race, diabetes, smoking, ASCVD, left ven-tricular hypertrophy (LVH), BMI, participants’ prioruse of BP drugs, and practice type setting, geo-graphic region, and research experience of the clin-ic the participant visited. In addition, intensifica-tion of treatment was examined in the setting ofuncontrolled BP during follow-up.


RESULTSThe baseline characteristics of participants, overalland by subgroups, are presented in Table I. Blackand nonblack participants had similar SBP, but DBPwas 1–2 mm Hg higher in both black men andwomen. Older participants (≥70 years) had a slight-ly higher mean SBP (146 mm Hg) and a lower meanDBP (81 mm Hg) than younger participants (55–69years) (144/85 mm Hg). Diabetic participants had alower mean DBP (82 mm Hg) than nondiabetics (84mm Hg), but the mean SBP was similar in bothgroups (145 mm Hg). Persons with LVH by electro-cardiogram (ECG) had a higher mean SBP (148 mmHg) than those without (145 mm Hg). Participantsin the West and Midwest had the lowest mean BP(144/82 mm Hg) compared with those in Canada,Puerto Rico, and the Virgin Islands (146–147/85–87mm Hg). Mean BP at baseline ranged from 143/81mm Hg among Veterans Affairs participants, 93%of whom were on antihypertensive treatment, to146/84 mm Hg among private practice participants,of whom 89% were on treatment.

Blood pressure control of participants at base-line, 6 months, and annual visits is displayed inTable II. Mean SBP/DBP decreased from 145/83mm Hg at baseline to 135/75 mm Hg at 5 years. BPcontrol increased from 27.4% at baseline to65.6% over this period. The percent remaining onStep 1 study drug decreased to 88.7% at 6 monthsand further decreased to 79.0% at 5 years. Themean number of drugs increased over the course ofthe trial from 1.3 at 6 months to 2.0 at 5 years. Ananalysis of BP control in a cohort of 19,803 par-ticipants who attended follow-up visits throughout4 years of follow-up was remarkably similar to theone which included all follow-up data, indicatingthat loss to follow-up did not appear to be animportant source of bias in estimating BP control(data not shown).

Blood pressure control of participants at base-line and follow-up, stratified by subgroups, is pre-sented in Table III. From baseline through year 5,the best control was in nonblack men (70.0%) andthe lowest in black women (58.8%). Control wasbetter throughout follow-up in younger partici-pants and those with pre-existing ASCVD. In con-trast, BP control was consistently worse in partici-pants with other comorbid conditions (diabetes,obesity, LVH, and elevated creatinine) even thougha greater proportion of such participants were onmultiple drugs as compared with those withoutthese conditions.

The frequency distribution of SBP and DBP atbaseline and at 3 years is shown in Figure 1.

Compared to baseline, both BP distributions at 3years are shifted to the left. After 3 years 35.6% ofparticipants still had SBP ≥140 mm Hg, but only8% were ≥160 mm Hg. Among participants withSBP ≥140 mm Hg at 3 years, more than half hadSBP 140–149 mm Hg and 77% had SBP 140–159mm Hg. Also, after 3 years only 10%, 3.6%, and1.8% had DBP ≥90, 95, and 100 mm Hg, respec-tively. Figure 2 depicts the percent at goal over timealong with the percent of participants on 1, 2, 3, or4+ drugs. Participants began treatment on mono-therapy with the blinded study drug. The percent ofparticipants who remained on one drug was 71%at 6 months of follow-up but had decreased to 36%by 5 years. The percent on two drugs increasedfrom 22% at 6 months to 35% at 5 years. Amongparticipants who achieved a BP <140/90 mm Hgafter 5 years, 40% were on one agent, 35% re-quired two agents, and 23% required three or more(data not shown).

The results from logistic regression analyses arepresented in Table IV. An odds ratio (OR) greaterthan 1.0 implies that a characteristic is associatedwith better BP control than the reference category.All except two factors listed were statistically sig-nificant univariate predictors of goal BP at 3 years.The exceptions were current smoking and havingbeen on BP treatment at baseline. In the multivari-able analysis, younger participants, men, non-blacks, nondiabetics, leaner individuals (BMI <30),those with lower baseline SBP, those without LVH,and those not on treatment at entry were morelikely to have better BP control than their referencegroups. The largest relative difference in BP controlwas found in the black/nonblack race comparison,where blacks were 31% less likely to be controlled(OR 0.69; 95% confidence limits: 0.65–0.73) thannonblacks. Better BP control was also observed inparticipants enrolled at clinics with no researchexperience when compared with those at clinicswith experience. Participants treated at nonprivatepractice clinics tended to have better BP controlthan those at private clinics. Participants in clinicslocated in Canada, Puerto Rico, or the VirginIslands were more likely to have better BP controlthan clinics in the Western United States, whereasparticipants in clinics located in the South tendedto have worse BP control.

In the multivariable analysis for treatment withtwo or more antihypertensive agents at 36 monthsof follow-up, the following characteristics wereassociated with a significantly greater chance (OR>1.0) of being on more medications: higher base-line SBP, male sex, atherosclerotic vascular disease,



Tab

le I

. Bas

elin

e C

hara

cter

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cs o

f Pa

rtic

ipan

ts E

nrol

led

in t

he A

LL

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T H

yper

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Tri

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GR

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IZE

N

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(YEA

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MEA

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BP (M

M H

G)

MEA

NH

R (B

PM)

MEA

NBM

I (K

G/M

2 )M

EAN

CR*

(MG

/DL)

MEA

NG

LUC

OSE

(MG

/DL)

MEA

NT

C (M

G/D

L)M

EAN

LDL

(MG

/DL)

MEA

NH

DL

(MG

/DL)

MEA

NT

G (M

G/D

L)

MEA

N

AL

L33

,357

100.

066

.914

4.8

83.3

73.6

29.7

1.02

124.

621

6.1

135.

646

.817

2.1

Wom

en

Bla

ck64

3019

.366

.414

5.4

83.9

75.4

31.6

0.96

132.

522

6.0

143.

355

.313

7.9

N

onbl

ack

9208

27.6

67.6

145.

382

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8712

3.2

227.

513

9.4

49.7

194.

1M

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Bla

ck53

6216

.166

.114

4.4

84.9

73.7

28.9

1.20

123.

420

7.3

133.

247

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4.8

N

onbl

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12,3

5737

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122.

320

6.5

129.

940

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8.5

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diab

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Y

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36.2

66.6

144.

782

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2.3

215.

513

3.9

44.9

188.

4

No

21,2

9463

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4.9

84.0

72.7

28.9

1.03

97.8

216.

413

6.5

47.9

162.

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ears

55

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21,5

6764

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4.3

84.7

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30.5

0.99

127.

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7.5

136.

446

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8.3

≥7

011

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35.3

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47.7

160.

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7303

21.9

64.1

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284

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4.7

47.6

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No

26,0

5478

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4.7

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30.1

1.02

128.

221

6.4

135.

946

.617

3.8

ASC

VD

pre

sent

Y

es15

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46.8

68.2

144.

482

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6.0

215.

813

5.7

46.2

172.

3

No

17,7

6053

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5.3

84.1

74.4

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1.00

132.

221

6.3

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547

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784

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217.

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3

SBP=

syst

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blo

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P=di

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seru

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555

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0.02

59 m

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DL

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s M

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ters

(48

site

s), u

nive

rsity

-bas

ed c

linic

s (7

1 si

tes)

, Vet

eran

s A

ffai

rs M

edic

al C

ente

rs (7

0si

tes)

, and

any

set

ting

othe

r th

an th

e pr

eced

ing

cate

gori

es (7

5 si

tes)

; 717

par

ticip

ants

wer

e fr

om s

ites

for

whi

ch p

ract

ice

setti

ng w

as n

ot k

now

n.

obesity, prior treatment, ECG LVH, and universityor Veteran Affairs medical center sites comparedwith private or health maintenance organization(HMO) sites. The following were associated with asignificantly lower chance (OR <1.0) of being ontwo or more drugs at 36 months compared withtheir corresponding reference groups: older age,black race, and smokers. Similarly, participants atsites in the Eastern or Southern United States, orPuerto Rico and the Virgin Islands were less likelyto be on two or more drugs than those at sites inthe Western United States.

Table V displays BP control status for partici-pants prescribed two or more antihypertensivedrugs, the percentage of uncontrolled participantswho had or did not have their drug regimen“stepped up” at the visit, and the mean BPs forthose not controlled, according to whether or notthere was a step up in drug regimen. A “step up”in drug regimen was defined as either an increasein the blinded (Step 1) drug, an increase in thenumber of drugs prescribed, or a change in pre-scription without a change in number of drugs. Forparticipants whose BP was uncontrolled at a givenvisit, the percentage stepped up decreased from64% at 6-month visits to only about 30% at thesecond through fifth year visits. The mean SBP forthose stepped up was generally about 4 mm Hghigher than those not stepped up; the DBP wasabout 1 mm Hg higher. Participants not stepped uphad mean SBP in the 151–154 mm Hg range.

DISCUSSIONThe BP control rate (66%) and the mean BP levels(135/75 mm Hg) achieved after 5 years of partici-pant follow-up in ALLHAT should be considered

an example of what may be achieved in the man-agement of most hypertensive patients, since themajority of study sites in ALLHAT were in com-munity practice settings. This high rate of BP con-trol was achieved despite recruiting a populationenriched with subgroups more difficult to control,such as blacks, the elderly, and diabetics, anddespite the limitation on the selection of drug class-es to add to the blinded therapy. Comparisons withother studies must be qualified by the potentialeffects of selective nonresponse, probably a largerissue for missed visits in follow-up studies such asALLHAT than with surveys such as NHANES. InALLHAT, it is possible that some participants whostopped attending clinics had easily controlled BPand consequently discontinued medication, whileothers had difficult-to-control BP and left ALL-HAT clinics due to dissatisfaction with care.

ALLHAT is the largest prospective randomizedtrial ever completed to examine the control ofhypertension and the effects of antihypertensivedrugs on clinical outcomes.13 It was conducted in avariety of clinical practice settings in North Americaand the Caribbean and in a diverse population ofolder hypertensive patients at high risk for cardio-vascular events by virtue of comorbid conditions orprevious cardiovascular events.13,14 ALLHAT hasthe largest number of blacks and the largest numberof diabetics of any hypertension treatment trial con-ducted. We believe that the ALLHAT population isrepresentative of the middle-aged and older hyper-tensive population frequently seen in practice set-tings. Although participants with stage 3 or moresevere hypertension were not included, they repre-sent a small minority of hypertensives in the uncon-trolled category.


Table II. Blood Pressure Control in ALLHAT Participants at Baseline, at 6 Months of Follow-Up, and AnnuallyThrough 5 Years of Follow-Up

SBP DBP NUMBER OF DRUGSTIME INTRIAL

NUMBERWITHVISIT MEAN MEAN SD

BP <140/90MM HG

%

SBP <140MM HG

%

DBP <90MM HG

%

ON STEP 1DRUG

%

Baseline 33,357 144.8 83.3 – – 27.4 30.9 68.1 –

6 Months 30,908 140.0 80.5 1.3 0.6 49.8 52.4 82.0 88.7

Year 1 28,102 138.1 79.3 1.4 0.7 55.2 57.9 85.6 85.7

Year 2 26,372 137.0 78.3 1.6 0.8 58.0 60.4 87.6 82.7

Year 3 24,338 135.6 77.1 1.7 0.9 62.3 64.2 89.9 81.2

Year 4 21,201 134.7 76.4 1.8 1.0 65.3 67.0 91.4 79.8

Year 5 12,210 134.7 75.3 2.0 1.0 65.6 67.1 92.4 79.0

SBP=systolic blood pressure; DBP=diastolic blood pressure; BP=blood pressure; SD=standard deviation;mm Hg=millimeters mercury


Tab

le I

II. B

lood

Pre

ssur

e C

ontr

ol (

%SB

P/D

BP

<140

/90

mm

Hg)

and

Med

icat

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Use

in A

LL

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T P

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nts,

by

Sele

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R 5

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S (%

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O. D

RU

GS

(%)

NO

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UG

S (%

)N

O. D

RU

GS

(%)

SUB

GR

OU

P(B

ASE

LIN

EC

HA

RA

CT

ER

IST

IC)*

%C

NT

R%

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DS

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NT

R≥2

≥3%

CN

TR

≥2≥3

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NT

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AL

L27

.490

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lack

wom

en26

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.723

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847

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.217

.358

.859

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B w

omen

26.0

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ears

26.2

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ASC

VD

abs

ent

26.0

89.1

47.6

23.8

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53.3

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17.0

65.1

60.6

26.7

Obe

se (

BM

I ≥3

0)†

27.8

91.8

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28.1

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.893

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.162

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.527

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(by

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944

.747

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No

28.0

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U

nkno

wn

25.9

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58.8

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Geo

grap

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Reg

ion¶

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ast

25.6

88.1

52.6

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3.9

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idw

est

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66.7

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uth

29.5

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est

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anad

a21

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.93.

560

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.114

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.00.

0

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VI

18.8

92.2

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Prac

tice

Set

ting

§

Pr

ivat

e24

.889

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.83.

854

.831

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.245

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.423

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O25

.094

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.123

.55.

265

.431

.06.

967

.543

.414

.471

.756

.623

.8

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m H

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28.8

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60.7

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20.3

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61.8

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nive

rsit

y28

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.449

.330

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.837

.78.

862

.454

.117

.868

.662

.924

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VA

MC

32.6

92.5

52.4

33.7

5.8

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43.6

11.0

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50.7

25.3

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34.9

O

ther

30.0

90.2

50.1

27.6

5.2

54.2

36.3

8.6

63.4

61.8

19.1

67.7

63.8

27.7

SBP=

syst

olic

blo

od p

ress

ure;

DB

P=di

asto

lic b

lood

pre

ssur

e; N

B=n

onbl

ack

race

; ASC

VD

=ath

eros

cler

otic

car

diov

ascu

lar

dise

ase;

BM

I=bo

dy m

ass

inde

x; B

P m

eds=

bloo

dpr

essu

re m

edic

atio

ns; %

Cnt

r=pe

rcen

t with

con

trol

led

BP;

No.

=num

ber;

mm

Hg=

mill

imet

ers

mer

cury

; LV

H=l

eft v

entr

icul

ar h

yper

trop

hy; E

CG

=ele

ctro

card

iogr

am*T

he s

ampl

e si

zes

for

base

line

med

icat

ion

stat

us a

nd s

erum

cre

atin

ine

leve

l are

, res

pect

ivel

y: 3

0,08

9 on

blo

od p

ress

ure

(BP)

med

icat

ion;

326

8 no

t on

BP

med

icat

ion;

2038

wit

h a

mea

n se

rum

cre

atin

ine

≥1.5

mg/

dL; a

nd 3

1,31

9 w

ith

seru

m c

reat

inin

e be

low

1.5

mg/

dL. F

or t

he o

ther

gro

ups,

sam

ple

size

s ar

e gi

ven

in T

able

I. T

heno

nbla

ck r

ace-

sex

cate

gori

es in

clud

e ap

prox

imat

ely

12%

non

blac

k H

ispa

nics

. † Bod

y m

ass

inde

x un

its

are

kg/m

2 ; ser

um c

reat

inin

e un

its

are

mg/

dL (

conv

ersi

on f

acto

rfo

r SI

uni

ts is

88.

4 µm

ol p

er m

g/dL

); ¶ U

S ce

nsus

reg

ions

. § See

lege

nd f

or T

able

I. ‡ E

CG

LV

H d

efin

ed a

s M

inne

sota

cod

e 3.

1 w

ith

any

4.1-

4.3

or 5

.1-5

.3 c

ode.

The ALLHAT participants were older on averageand more likely to be on antihypertensive drug treat-ment at baseline than the 1988–1991 NHANES IIIpopulation, who were surveyed in the years prior to the initiation of recruitment for ALLHAT.1 Never-theless, the proportion of the ALLHAT participantswith BP controlled (<140/90 mm Hg) prior to thestudy at screening (27.4%) was virtually identical tothe BP control rate in the adult noninstitutionalizedrepresentative population in NHANES III. Therefore,the rapid improvement in the BP control rates in ALL-HAT demonstrates what can be achieved by setting a

BP goal that is consistently reinforced, monitoringcontrol rates, providing feedback to physicians abouttheir performance in meeting the BP goal, and using aspecific protocol for increasing doses and addition ofantihypertensive medications to the regimen.

The ALLHAT regimens were more restrictivethan what may be used in clinical practice, sincethe investigators could not routinely add any of thefour classes of agents to which participants wereallocated at randomization: a diuretic, an ACEinhibitor, a calcium channel blocker, or an alphablocker. The first three of these are among the most


Figure 1. Frequency distribution of systolic blood pressure (SBP) and diastolic blood pressure (DBP) for ALLHATparticipants at the initial clinic visit and after 36 months of follow-up

commonly used classes for the management ofhypertension. Only atenolol, clonidine, reserpine,and/or hydralazine were provided in the trial to beadded to the blinded drugs to attempt to achieve BPcontrol. For example, the addition of a β blocker ina participant randomized to an ACE inhibitor mightbe expected to lower BP less than the addition of adiuretic, which was not routinely permitted. Theproportion of participants treated with two or moredrugs increased from 26% at 6 months to 62% at 5years (Table V). However, among participants withuncontrolled BP, the proportion whose regimenswere stepped up leveled off at around 30% by year2, suggesting that even better BP control rates couldhave been achieved with further medication titrationas prescribed by the protocol.

The BP control achieved in ALLHAT was superiorto the control rates among treated hypertensives sur-veyed in NHANES III, where BP <140/90 mm Hg wasfound in 30%–45% of those who had hypertensionand reported taking antihypertensive medications.1ALLHAT BP control rates also greatly exceeded con-trol rates (25%) in treated hypertensive patients whowere regularly being seen by physicians in primarycare medicine clinics in several Veterans Affairs Medi-cal Centers in the New England area.6

Several other large hypertension trials begun after ALLHAT was initiated have had the same BP

goals.17,18 In the Losartan Intervention For EndpointReduction in Hypertension (LIFE) trial,18,19 an an-giotensin receptor blocker (losartan)-based regimenwas compared with a β blocker (atenolol)-based reg-imen in 9193 participants. A diuretic was routinelyadded to either regimen to achieve BP control, and anyother antihypertensive drug class could be addedexcept for another angiotensin receptor blocker, a βblocker, or an ACE inhibitor. After 4.8 years of follow-up, BP control (≤140/90 mm Hg rather than <140/90mm Hg) was only 49% and 46% in the losartan andatenolol groups, respectively. In the Controlled OnsetVerapamil Investigation of Cardiovascular Endpoints(CONVINCE) trial,17 a regimen beginning with a cal-cium channel blocker (controlled-onset, extendedrelease verapamil) was compared with a regimen be-gun with the investigator’s choice of either a diuretic(hydrochlorothiazide) or a β blocker (atenolol).After 30 months of follow-up, 67% of CON-VINCE participants achieved BP <140/90 mm Hg,very similar to what was achieved in ALLHAT witha more restrictive regimen. The lower control ratesin LIFE may be related to: 1) higher entry BP crite-ria and baseline BP; 2) ECG LVH in all participants,which predicted a lower likelihood of controllingBP in ALLHAT; 3) fewer medications available toadd to the BP regimen; and 4) the different thresh-olds for treatment and treatment goals amongEuropean/Scandinavian investigators in LIFE.19

In all of these trials, SBP was the primary determi-nant of the control rates, since DBP was usually con-trolled in over 90% of the trial participants. In ALL-HAT DBP was <90 mm Hg in 92% of participantswhile SBP was <140 mm Hg in 67%. A major factorthat contributes to this difference is the preponder-ance of isolated systolic hypertension in this olderstudy population: over 80% of untreated or treatedbut uncontrolled hypertensive individuals over age 60years have isolated systolic hypertension.20 Othercontributing factors may include the historicalemphasis on DBP control throughout most of the20th century in clinical practice and in drug develop-ment, the higher doses and numbers of drugs neededto achieve the SBP target, and the reluctance of inves-tigators to prescribe, and participants to take, thelarge doses and number of medications often requiredto achieve SBP control. Additionally, a greater pro-portion of older hypertensive individuals have muchfarther for SBP to fall compared with DBP to reachthe 140/90 mm Hg goal.

An average of two drugs was required to achieveBP control in two thirds of participants, primarily tocontrol SBP. The number of drugs needed to controlthe majority of participants was greater than was


Figure 2. Percent of ALLHAT participants who achievedtheir goal blood pressure (SBP/DBP <140/90 mm Hg)among those attending follow-up visits (dashed line) andproportions at those visits who were prescribed 1, 2, 3,or 4+ antihypertensive medications (solid lines)

anticipated when ALLHAT was designed. Althoughmedications were often increased for lack of BP con-trol, intensification of therapy was not carried out for many participants with controlled DBP but SBP between 140–159 mm Hg. However, after36 months of follow-up, approximately twice asmany participants had SBP levels of 140–149 mmHg compared with 150–159 mm Hg (Figure 1). Itis very likely that better BP control rates could havebeen achieved if therapy were intensified more con-sistently for persistent SBP ≥140 mm Hg. Judged bylevels at which treatment was or was not steppedup, some ALLHAT clinicians seemed satisfied witha typical SBP in the low 150s, similar to what Hymanand Pavlik9 observed in NHANES III data. With thegreater variety of medications available in clinical

practice, it is reasonable to expect that even higherrates of control could be achieved in a “real world”practice setting. These data suggest that the majorityof hypertensive patients will require at least two anti-hypertensive medications to achieve a BP goal of<140/90 mm Hg. For lower goals, such as is recom-mended in patients with diabetes, even more drugslikely may be needed.

In multiple logistic regression analysis, higher base-line SBP, older age, black race, and living in theSoutheastern United States predicted a lower likeli-hood of achieving BP control in ALLHAT, confirmingfindings of some previous studies.19,21 Baseline level of BP, black race, older age, and living in theSoutheastern United States were the strongest predic-tors of lack of control with some antihypertensive


Table IV. Multiple Logistic Analysis of Relative Odds of Blood Pressure Control and Relative Odds of Being on Twoor More Drugs at 36 Months of Follow-Up for Selected Baseline Characteristics

BLOOD PRESSURE CONTROLLED ON TWO OR MORE DRUGSUNIVARIATE FULL MODEL UNIVARIATE FULL MODEL

BASELINECHARACTERISTIC

REFERENCECATEGORY

ODDSRATIO†

95% CL ODDSRATIO†

95% CL ODDSRATIO‡

95% CL ODDSRATIO‡

95% CL

Visit 1 SBP, mm Hg (10 mm Hgincrease)

0.82* (0.80, 0.84) 0.79* (0.77, 0.80) 1.09* (1.07, 1.11) 1.22* (1.19, 1.24)

Age (10-yearincrease)

0.92* (0.89, 0.95) 0.93* (0.89, 0.97) 0.91* (0.89, 0.94) 0.84* (0.81, 0.87)

Male (Female) 1.17* (1.11, 1.24) 1.10* (1.03, 1.18) 1.40* (1.34, 1.47) 1.15* (1.09, 1.22)Black (Nonblack) 0.69* (0.65, 0.73) 0.75* (0.71, 0.80) 0.90* (0.86, 0.95) 0.89* (0.84, 0.94)Type 2 diabetic (No) 0.84* (0.79, 0.88) 0.86* (0.80, 0.91) 1.02 (0.97, 1.07) 0.98 (0.93, 1.04)Smoker (No) 1.03 (0.97, 1.10) 0.96 (0.89, 1.04) 0.84* (0.80, 0.89) 0.80* (0.75, 0.86)ASCVD (No) 1.10* (1.04, 1.16) 1.02 (0.96, 1.09) 1.15* (1.10, 1.21) 1.09* (1.03, 1.15)BMI ≥30 kg/m2 (No) 0.87* (0.83, 0.92) 0.92* (0.86, 0.98) 1.21* (1.15, 1.26) 1.16* (1.10, 1.22)Prior treatment (No) 0.91 (0.84, 1.00) 0.68* (0.61, 0.75) 2.17* (1.99, 2.37) 2.94* (2.66, 3.25)Creatinine ≥1.5 mg/dL (No) 0.79* (0.70, 0.88) 0.88 (0.78, 1.00) 1.14* (1.04, 1.25) 1.06 (0.96, 1.18)ECG LVH (No) 0.69* (0.60, 0.80) 0.85* (0.73, 0.99) 1.25* (1.11, 1.41) 1.20* (1.05, 1.36)Clinic research exp (No) 0.93* (0.88, 0.99) 0.90* (0.83, 0.96) 1.23* (1.17, 1.29) 0.95 (0.89, 1.01)Practice setting HMO (Private) 1.26* (1.07, 1.49) 1.19 (0.97, 1.45) 0.62* (0.54, 0.71) 0.91 (0.77, 1.07) Comm Hlth Ctr (Private) 0.94 (0.85, 1.03) 1.14* (1.02, 1.28) 1.16* (1.07, 1.26) 0.98 (0.90, 1.08) University (Private) 1.01 (0.92, 1.10) 1.09 (0.99, 1.21) 1.34* (1.24, 1.45) 1.12* (1.03, 1.22) VAMC (Private) 1.03 (0.96, 1.10) 1.05 (0.96, 1.14) 2.10* (1.97, 2.23) 1.69* (1.56, 1.82) Other (Private) 1.05 (0.95, 1.16) 1.19* (1.06, 1.32) 1.06 (0.98, 1.15) 0.92 (0.83, 1.01)Geographic region East (West) 0.98 (0.88, 1.09) 1.10 (0.98, 1.23) 0.76* (0.69, 0.83) 0.74* (0.67, 0.82) Midwest (West) 0.91 (0.82, 1.01) 0.98 (0.88, 1.09) 1.05 (0.97, 1.15) 0.95 (0.86, 1.04) South (West) 0.73* (0.66, 0.80) 0.84* (0.76, 0.92) 0.84* (0.78, 0.91) 0.84* (0.77, 0.91) Canada (West) 1.50* (1.21, 1.86) 1.50* (1.19, 1.89) 1.00 (0.84, 1.20) 0.93 (0.77, 1.14) Puerto Rico & VI (West) 1.32* (1.18, 1.49) 1.42* (1.24, 1.61) 0.27* (0.24, 0.30) 0.29* (0.26, 0.32)

CL=confidence limits; SBP=systolic blood pressure; DBP=diastolic blood pressure; SD=standard deviation;ASCVD=atherosclerotic cardiovascular disease; BMI=body mass index; VI=US Virgin Islands; HMO=health maintenanceorganization; Comm Hlth Ctr=community health center; VAMC=Veterans Affairs Medical Centers; LVH=left ventricularhypertrophy; ECG=electrocardiogram*p-value <0.05. †An odds ratio >1.0 implies characteristic is associated with better BP control than the referencecategory; odds ratio <1.0 is associated with worse BP control. ‡An odds ratio >1.0 implies participants withcharacteristic or in group are more likely to have been prescribed two or more antihypertensive drugs than thereference category; odds ratio <1.0 implies participants are less likely to have been prescribed two or more drugs.

drugs used as monotherapy in the Veterans AffairsSingle-Drug Therapy Study.21 ALLHAT identifiedadditional factors associated with lower BP controlrates. These included female sex, diabetes, obesity,prior antihypertensive therapy, ECG LVH, and care ina private practice setting or a clinic where the investi-gator had prior clinical research experience. Thisanalysis cannot explain these associations. In somecases, they may result from physiological or lifestyledifferences that might be expected to result in poorerBP control. In other cases, they may result from differ-ences in practice patterns by the investigators or med-ication adherence by the participants. Some of thegroups with lower BP control rates, e.g., blacks,women, and older-aged participants, were less likely tobe on two or more antihypertensive medications.There is evidence that arteries are stiffer in type 2diabetics, resulting in higher SBP levels and pulsepressure for age.22,23 This may have contributed to greater resistance in lowering SBP in diabetics. The presence of target organ damage, such as LVHand prior antihypertensive therapy, most likely repre-sents more severe hypertension. There are likelyunmeasured factors that contribute to the differencesseen, and we did not formally model the undoubtedlycomplex reciprocal relationship between BP controland changes in medication over time. Our study can-not assess the potential contributions to BP control ofavailability of medical care or cost of care, includingmedications. All of the antihypertensive medicationsthat were prescribed by the ALLHAT protocol wereprovided to the participants without cost.

In summary, the ALLHAT trial provides com-pelling evidence that BP control rates can be marked-ly increased to at least two thirds of the treatedhypertensive population. Most of the participants

who did not achieve goal BPs had persistent elevationof SBP. Many of these were not titrated to the maxi-mum doses or numbers of drugs permitted in thetrial, and more aggressive treatment of SBP couldhave yielded even better BP control rates in ALL-HAT. Various factors that are associated with lowerBP control rates were identified. Nevertheless, it islikely that the overwhelming majority of hyperten-sive patients could achieve BP control with the use of multiple antihypertensive medications availabletoday and the use of tracking and feedback systemsto monitor patient progress.

Acknowlegement: This study is supported by contract with theNational Heart Lung and Blood Institute (NHLBI). The ALL-HAT investigators acknowledge contributions of study medica-tions supplied by Pfizer, Inc. (amlodipine and doxazosin),AstraZeneca (atenolol and lisinopril), and Bristol-Myers Squibb(pravastatin), and financial support provided by Pfizer.

REFERENCES1 Burt VL, Whelton P, Roccella EJ, et al. Prevalence of hyperten-

sion in the US adult population. Results from the Third NationalHealth and Nutrition Examination Survey, 1988–1991.Hypertension. 1995;25:305–313.

2 Joint National Committee on Prevention, Detection, Eval-uation, and Treatment of High Blood Pressure: the sixth reportof the Joint National Committee on Prevention, Detection,Evaluation, and Treatment of High Blood Pressure. Arch InternMed. 1997;157:2413–2446.

3 Mulrow P. Hypertension: a worldwide epidemic. In: Black HR,Izzo JI Jr, eds. Hypertension Primer, Second Edition, TheEssentials of High Blood Pressure. Dallas, TX; AmericanHeart Association; 1999:271–273.

4 Julius S. Worldwide trends and shortcomings in the treatmentof hypertension. Am J Hypertens. 2000;13:57S–61S.

5 Meissner I, Whisnant JP, Sheps SG, et al. Detection and controlof high blood pressure in the community: do we need a wake-up call? Hypertension. 1999;34:466–471.

6 Berlowitz DR, Ash AS, Hickey EC, et al. Inadequate manage-ment of blood pressure in a hypertensive population. N Engl JMed. 1998;339:1957–1963.


Table V. Blood Pressure Control† Status Among Participants Prescribed Two or More Antihypertensive Drugs DuringFollow-Up, and the Percentage of Uncontrolled Participants Who Had Their Drug Regimen Stepped Up‡ at the Visit

PRESCRIBED TWO OR MORE ANTIHYPERTENSIVE DRUGSBP UNCONTROLLED

ALL BP CONTROLLED† NOT STEPPED UP‡ STEPPED UP‡

FOLLOW-UP VISIT

NUMBERWITHVISIT

N (%)¶ N (%) N (%) SBP DBP N (%) SBP DBP

6 Months 30,908 8168 (26.4) 2940 (36.0) 1903 (39.4) 153.6 84.7 3325 (63.6) 157.7 86.2Year 1 28,102 9843 (35.0) 4326 (44.0) 3257 (59.0) 153.1 83.8 2260 (41.0) 156.4 84.7Year 2 26,372 11,600 (44.0) 5774 (49.8) 3933 (67.5) 152.2 82.5 1893 (32.5) 155.3 83.4Year 3 24,338 12,266 (50.4) 6858 (55.9) 3748 (69.3) 151.5 81.5 1660 (30.7) 154.1 82.4Year 4 21,201 11,939 (56.3) 7208 (60.4) 3401 (71.9) 151.0 80.9 1330 (28.1) 154.8 81.7Year 5 12,210 7627 (62.5) 4685 (61.4) 2108 (71.7) 150.9 79.6 834 (28.3) 154.7 80.4

†Blood pressure (BP) control defined as systolic BP(SBP)/diastolic BP(DBP)<140/90 mm Hg; ‡A “step up” in drug regimenwas defined as either an increase in the dose of the blinded (Step 1) drug, an increase in the number of drugs prescribed,or a change in prescription without a change in number of agents. No information was available on change in doses ofdrugs other than the blinded drug, so it is likely the percent stepped up is underestimated. ¶Percentage of those with visit.

7 The fifth report of the Joint National Committee on Detection,Evaluation, and Treatment of High Blood Pressure (JNC V). Arch Intern Med. 1993;153:154–183.

8 World Health Organization-International Society of Hyper-tension Guidelines Subcommittee. 1999 World Health Org-anization-International Society of Hypertension guidelinesfor the management of hypertension. J Hypertens. 1999;17:151–183.

9 Hyman DJ, Pavlik VN. Characteristics of patients with uncon-trolled hypertension in the United States. N Engl J Med. 2001;345:479–486.

10 The ALLHAT Officers and Coordinators for the ALLHATCollaborative Research Group. Major cardiovascularevents in hypertensive patients randomized to doxazosin vs.chlorthalidone: the Antihypertensive and Lipid-LoweringTreatment to Prevent Heart Attack Trial (ALLHAT).JAMA. 2000;283:1967–1975.

11 Davis BR, Cutler JA, Gordon DJ, et al., for the ALLHATResearch Group. Rationale and design for the Antihypertensiveand Lipid-Lowering Treatment to Prevent Heart Attack Trial(ALLHAT). Am J Hypertens. 1996;9:342–360.

12 Cutler JA, Gordon DJ, Davis BR, et al. Rationale and design forthe Antihypertensive and Lipid-Lowering Treatment to PreventHeart Attack Trial (ALLHAT). In: Black HR, ed. Clinical Trialsin Hypertension. New York, NY: Marcel Dekker; 2001:531–586.

13 Grimm RH, Margolis KL, Papademetriou V, et al., for theALLHAT Collaborative Research Group. Baseline characteris-tics of participants in the Antihypertensive and Lipid-LoweringTreatment to Prevent Heart Attack Trial (ALLHAT).Hypertension. 2001;37:19–27.

14 Wright JT, Cushman WC, Davis BR, et al., for the ALLHATGroup. The Antihypertensive and Lipid-Lowering Treatmentto Prevent Heart Attack Trial (ALLHAT): clinical centerrecruitment experience. Control Clin Trials. 2001;22:659–673.

15 Pressel S, Davis BR, Louis, GT, et al., for the ALLHAT ResearchGroup. Participant recruitment in the Antihypertensive andLipid-Lowering Treatment to Prevent Heart Attack Trial (ALL-HAT). Control Clin Trials. 2001;22:674–686.

16 Dunnett CW. A multiple comparisons procedure for comparingseveral treatments with a control. J Am Stat Assoc. 1955;60:573–583.

17 Black HR, Elliott WJ, Neaton JD, et al. Baseline characteristicsand early blood pressure control in the CONVINCE trial.Hypertension. 2001;37:12–18.

18 Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascularmorbidity and mortality in the Losartan Intervention ForEndpoint reduction in hypertension study (LIFE): a randomisedtrial against atenolol. Lancet. 2002;359:995–1003.

19 Kjeldsen SE, Dahlof B, Devereux RB, et al. Lowering of bloodpressure and predictors of response in patients with left ven-tricular hypertrophy: the LIFE study. Losartan InterventionFor Endpoint. Am J Hypertens. 2000;13:899–906.

20 Franklin SS, Jacobs MJ, Wong ND, et al. Predominance of iso-lated systolic hypertension among middle-aged and elderly UShypertensives. Analysis based on National Health andNutrition Examination Survey (NHANES) III. Hypertension.2001;37:869–874.

21 Cushman WC, Reda DJ, Perry HM, et al., for the Departmentof Veterans Affairs Cooperative Study Group on Anti-hypertensive Agents. Regional and racial differences inresponse to antihypertensive medication use in a randomizedcontrolled trial of men with hypertension in the United States.Arch Intern Med. 2000;160:825–831.

22 Monnier VM, Kohn RR, Cerami A. Accelerated age-relatedbrowning of human collagen in diabetes mellitus. Proc NatlAcad Sci U S A. 1984:81:583–587.

23 Lo CS, Relf IRN, Myers KA, et al. Doppler ultrasound recog-nition of preclinical changes in arterial wall in diabetic subjects.Diabetes Care. 1986;9:27–31.


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