The Pressure of Getting the Blood Pressure Right: Hypertension 2017

William C. Cushman, MDChief, Preventive Medicine, Memphis VA Medical Center

Professor, Preventive Medicine, Medicine, PhysiologyUniversity of Tennessee Health Science Center

Memphis, Tennessee

Tennessee Chapter Scientific Meeting 2017 Franklin, TN, October 27, 2017

Presenter Disclosure Information

William C. Cushman, MD, FACP, FASH, FAHA

FINANCIAL DISCLOSURE:Institutional Grants: LillyUncompensated Consulting: Takeda, Novartis

The content does not necessarily represent the official views of the SPRINT or ACCORD Steering Committees, the NIH, the VA, or the U.S. government

• JNC 7 (2003)

– last comprehensive “evidence-based” HTN guideline in U.S.

– Sponsored by NHLBI/NIH

• JNC 8 Panel Report (2014)

– Evidence-based (systematic reviews)

– Developed under NHLBI sponsorship, but NHLBI stopped sponsoring

guidelines, so published by JNC 8 panel members

– Limited to: BP thresholds, goals, medication selection

• 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA

Guideline for the Prevention, Detection, Evaluation and Management of High

Blood Pressure in Adults

– Comprehensive, evidence-based; primary sponsors ACC & AHA

– To be presented November 13, 2017, at AHA Scientific Sessions

Most Relevant Hypertension Guidelines for U.S. Practitioners

Major Randomized Trials Testing SBP Goals in General (Older) Populations Prior to SPRINT

SHEP Syst-Eur HYVET JATOS VALISH

Age >60 >60 >80 65-85 70-84

Number 4,736 4,695 3,845 4,418 3,260

Entry SBP 160-219 160-219 160-199 >160 >160

Goal SBP <148 <150 <150 <140 <140

Achieved SBP 142 151 144 136 137

Stroke 36% 42% ns ns ns

CVD 32% 31% 34% ns ns

Mortality ns ns 21% ns ns

SBP = systolic blood pressure; CVD = cardiovascular disease

Diastolic BP Goal Trials

Several trials used DBP goal ~90 mm Hg and demonstrated consistent reduction of CVD events

• VA Cooperative Study- Entry: DBP 90-129 mm Hg- Goal: DBP <90 mm Hg

• Hypertension Detection and Follow-up Program (HDFP)- Entry: DBP ≥90 mm Hg- Goal: DBP ≤90 mm Hg and at least 10 mm Hg ↓

• Australian National Blood Pressure (ANBP) Trial- Entry: DBP 95 to <110 mm Hg- Goal: DBP ≤90 mm Hg initially, then after 1 year, lowered to ≤80 mm Hg

• STOP-Hypertension Trial- Entry: SBP 180-230 mm Hg + DBP ≥90 mm Hg, or DBP 105-120 mm Hg irrespective of SBP- Goal: BP <160/95 mm Hg

Current U.S. BP Goal Recommendations

JNC 8 (2014) ACP-AAFP (2017) VA/DoD (2014)

Age ≥60 years <150/90 (strong) <150 (strong) <150/90 (strong)

Stroke/TIA <140 (weak)

High CV Risk <140 (weak)

Age <60 years <140/90 (E/strong) N/A <150/90

(weak/strong

Diabetes <140/90 N/A <150(140)/85

(strong)

CKD <140/90 N/A <140/90

(CKD guidelines)

SPRINT Research QuestionWill CVD composite event rate be lower in intensive compared to standard SBP treatment (N = 9,361)?

Randomized Controlled Trial

Target Systolic BP

Intensive Treatment Goal SBP < 120 mm Hg

Standard TreatmentGoal SBP < 140 mm Hg

SPRINT design details available at:• ClinicalTrials.gov (NCT01206062)• Ambrosius WT et al. Clin. Trials. 2014;11:532-546.

SPRINT Inclusion/Exclusion Criteria• Age: ≥50 years old

• BP: systolic blood pressure : 130–180 mm Hg (treated or untreated)

• Additional cardiovascular disease (CVD) risk• Clinical or subclinical CVD (excluding stroke)• Chronic kidney disease (CKD), defined as eGFR 20–59 ml/min/1.73m2

• Framingham Risk Score for 10-year CVD risk ≥ 15%• Age ≥ 75 years

• Exclude for: • Stroke, Diabetes mellitus, Polycystic kidney disease, Congestive heart failure

Proteinuria >1g/d

• CKD with eGFR <20 mL/min/1.73m2 (MDRD)

• Adherence concerns

• Residing in nursing home or dementia Dx Clin. Trials. 2014;11:532-546

N Engl J Med. 2015;373:2103-16

TotalN=9361

Mean age 68 years

≥75 years 28%

Female 36%

White 58%

African-American 30%

Hispanic 11%

Prior CVD 20%

Mean 10-year Framingham CVD risk 24%

Taking antihypertensive meds 91%

Mean number of antihypertensive meds 1.8

Mean Baseline BP, mm Hg 140/78

Prior CKD 28%

SPRINT: Selected Baseline Characteristics

BP Measurement Methodology in SPRINT

• Similar to what has been used in virtually all HTN outcome

trials defining the recommended BP thresholds and goals

in guidelines.

• Similar to what has been recommended for clinical

practice by virtually all HTN guidelines around the world

for decades, including all JNCs, ASH/ISH, VA/DoD,

ESH/ESC, UK/NICE, Canadian/CHEP, Australian, ...

BP Measurement in SPRINT (Automated)

• Visit BP was the average of 3 seated office BP measurements obtained using an automated measurement device: Omron 907XL.

• Appropriate cuff size was determined by arm circumference.

• Participant was seated with back supported and arm bared and supported at heart level.

• Device was set to delay 5 minutes and then take/average 3 BP measurements, during which time participant refrained from talking.

Cushman, et al. Hypertension. 2016;67:263-5

Study N Routine Office BP Automated Office BP

Graves 104 152/84 136/79

Beckett 481 151/83 140/80

Myers-16 309 153/87 132/75

Myers-18 254 150/89 133/80

Myers-19 303 150/81 133/74

Mean 151/85 135/78

∆ = 16/7 mmHg

Routine Office BP versus Automated Office BP

Study N Location AOBP Awake ABP

Myers-15 62 HT Clinic 140/77 141/77

Myers-14 200 ABPM Unit 133/72 135/76

Myers-14 200 ABPM Unit 132/76 134/77

Myers-18

Beckett

254

481

ABPM Unit

Family Practice

133/80

140/80

135/81

142/80

Godwin 654 Family Practice 139/80 141/80

Myers-17 139 ABPM Unit 141/83 142/81

Myers -19 303 Family Practice 135/77 133/74

Andreadis 90 HT Clinic 140/88 136/87

Myers-20 100 ABPM Unit 137/79 139/80

Myers-16 309 ABPM Unit 132/75 134/77

Mean (no difference) 137/79 137/79

Automated Office BP versus Awake Ambulatory BP

Bland Altman plot showing mean difference between research grade and usual

clinic BP and their limits of agreement

-10

0-5

00

50

100 150 200

-50

05

0

20 40 60 80 100 120

Re

se

arc

h g

rad

e m

inu

s

usual clin

ic s

ysto

lic B

P

Average of usual clinic

minus research grade diastolic

Average of usual clinic

minus research grade systolic BP

Re

se

arc

h g

rad

e m

inu

s

Usual clin

ic d

iasto

lic B

P

Systolic

Diastolic

-12.7

-12.0

+20.7

-46.1

+10.1

-34.2

n=275 Research grade BP was on average 12.7/12.0 mmHg lower (bias) than routine clinic BP but also had wide limits of agreement

Agarwal R. J Am Heart Assoc.

2017;6:e004536.

One can’t just subtract x mm Hg from a poorly done clinic BP to approximate SPRINT BP, since the variation is large and unpredictable in an individual patient.

Systolic BP During Follow-up

Mean SBP136.2 mm Hg

Mean SBP121.4 mm Hg

Average SBP(During Follow-up)

Standard: 134.6 mm Hg

Delta: 13.5 mm Hg

Intensive: 121.5 mm Hg

Average number ofantihypertensivemedications

Number ofparticipants

Standard

Intensive

Year 1

Medication Classes by Treatment GroupLast Visit Per Participant Prior to 8/20/2015

3 major classes were used 22-24% more often in Intensive than Standard Group, but pattern of drug class usage was similar.

ASH, May 2016

Systolic BP Distribution by Treatment GroupMost Recent Visit Per Participant

< 120 < 130 < 140

14% 34% 71% Standard Participants

62% 80% 90% Intensive Participants

ASH 2016

Number ofParticipants

Hazard Ratio = 0.75 (95% CI: 0.64 to 0.89)

Standard

Intensive(243 events)

During Trial (median follow-up = 3.26 years)Number Needed to Treat (NNT)

to prevent a primary outcome = 61

SPRINT Primary Outcome (CVD)Cumulative Hazard

(319 events)

The SPRINT Research Group. N Engl J Med. 2015;373:2103-16

Hazard Ratio

P value

Primary Outcome

0.75 <0.001

Components

All MI 0.83 0.19

Non-MI ACS 1.00 0.99

All Stroke 0.89 0.50

All HF 0.62 0.002

CVD Death 0.57 0.005

25% reductionP<0.001

Adapt from Figure 2B in the N Engl J Med manuscript

Include NNT

All-cause MortalityCumulative Hazard

Hazard Ratio = 0.73 (95% CI: 0.60 to 0.90)

During Trial (median follow-up = 3.26 years)

Number Needed to Treat (NNT)to Prevent a death = 90

Standard(210 deaths)

Intensive(155 deaths)

Number ofParticipants

The SPRINT Research Group. N Engl J Med. 2015;373:2103-16

27% reduction P=0.003

Experience in the Six Pre-specified Subgroup Populations of Interest

Primary Outcome (CVD Composite) All Cause Mortality

(Treatment by subgroup interaction)

The SPRINT Research Group. N Engl J Med. 2015;373:2103-2116 *p=0.34, after Hommel adjustment for multiple comparisons

*

Cumulative Hazards for SPRINT Primary Outcome by Frailty Status

HR: 0.23 95% CI: 0.23 to 0.95 HR: 0.63 95% CI: 0.43 to 0.92 HR: 0.68 95% CI: 0.45 to 1.02

Interaction p-value = 0.838 JAMA. 2016;315:2673-82

Serious Adverse Events* (SAE) During Follow-up

All SAE reports (no different in age ≥75 yrs)

Number (%) of Participants

Intensive Standard HR (P Value)

1793 (38.3) 1736 (37.1) 1.04 (0.25)

SAEs associated with Specific Conditions of Interest

Hypotension 110 (2.4) 66 (1.4) 1.67 (0.001)Syncope 107 (2.3) 80 (1.7) 1.33 (0.05)Injurious fall (no different in age ≥75 yrs) 105 (2.2) 110 (2.3) 0.95 (0.71)Bradycardia 87 (1.9) 73 (1.6) 1.19 (0.28)Electrolyte abnormality 144 (3.1) 107 (2.3) 1.35 (0.020)Acute kidney injury or acute renal failure 193 (4.1) 117 (2.5) 1.66 (<0.001)

*Fatal or life threatening event, resulting in significant or persistent disability,requiring or prolonging hospitalization, or judged important medical event.

Number (%) of Participants with a

Monitored Clinical Measure During Follow-upNumber (%) of Participants

Intensive Standard HR (P Value)

Laboratory Measures1

Sodium <130 mmol/L 180 (3.9) 100 (2.2) 1.76 (<0.001)

Potassium <3.0 mmol/L 114 (2.5) 74 (1.6) 1.50 (0.006)

Potassium >5.5 mmol/l 176 (3.8) 171 (3.7) 1.00 (0.97)Signs and Symptoms

Orthostatic hypotension2 777 (16.6) 857 (18.3) 0.88 (0.013)

Orthostatic hypotension+dizziness 62 (1.3) 71 (1.5) 0.85 (0.35)

1. Detected on routine or PRN labs; routine labs drawn quarterly for first year, then q 6 months2. Drop in SBP ≥20 mm Hg or DBP ≥10 mm Hg 1 minute after standing (measured at 1, 6, and 12 months and yearly thereafter)

Influence of Baseline Diastolic BP on Effects of Intensive Compared to Standard

BP Control

Beddhu, et al. Circulation Oct 2017, online

Cubic spline regression curves relating baseline DBP as a continuous variable to the primary and

secondary outcomes

Beddhu, et al. Circulation Oct 2017, online

Median, 25th and 75th %iles of the patients’ mean followup SBP, DBP, MAP and PP, by randomized SBP intervention and quintile of baseline DBP (N=9119)

Beddhu, et al. Circ. Oct 2017

Primary CVD outcome, all-cause death and incident CKD in the standard and intensive SBP groups by quintile of baseline DBP

Beddhu, et al. Circulation Oct 2017, online

Summary: DBP Quintiles

• There were U-shaped relationships of baseline DBP with

the primary CVD outcome and all-cause death in

SPRINT.

• However, the beneficial effects of intensive SBP lowering

on the primary CVD outcome and all-cause death were

not modified by baseline level of DBP.

• Underlying processes (such as increased arterial stiffness) that

lead to a decline in DBP rather than the level of DBP per se might

be the reason for the observed associations of worse outcomes

with lower DBP.

• Low levels of DBP within the ranges examined in SPRINT should

not be an impediment to intensive treatment of hypertension, at

least in those without diabetes mellitus or stroke.

Summary: DBP Quintiles

Implications of SPRINT for HTN Treatment and Guidelines

SPRINT should change SBP goal recommendations in HTN guidelines:

• 2016 Canadian (CHEP) and Australian Heart Foundation guidelines recommend SBP <120 mm Hg in certain high-risk patients.

• 2017 ACP/AAFP guidelines recommend SBP <150 mm Hg in age ≥60 yrs, but consider <140 mm Hg if stroke/TIA or high CVD risk.

• US ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA HTN guidelines to be released November 13, 2017.

Letter in Annals in Response to ACP-AAFP HTN Guideline: W Cushman, K Johnson, W Applegate, J Cutler

• We agree with Qaseem and colleagues [ACP-AAFP

guideline] that there is strong evidence to support

an SBP goal <150 mm Hg in older adults with HTN.

• However, we believe that the authors underestimate

the strength of evidence for a goal <120 mm Hg that

is based on SPRINT …

• We urge clinicians to consider treating older

patients with HTN at higher risk for CVD … to a

lower SBP than ACP-AAFP HTN guideline

recommends and propose that guidelines now

reflect the strength of evidence from SPRINT.

Ann Intern Med. 2017 Aug 15;167:290-291.

RCTs Testing BP Goals In Hypertensive Diabetic Patients Prior to ACCORD BP

Trial nDuration

(years)

SBP goal,

mmHg

DBP goal,

mmHg

Mean BP, less

intense,

mmHg

Mean BP,

more

intense,

mmHg

Outcome

Risk Reduction

SHEP 583 5 <148 none 155/72 146/68

Stroke 22% (ns)

CVD 34%

CHD 56%

Syst-Eur 492 2 <150 none 162/82 153/78Stroke 69%

CVD 62%

HOT 1,501 3 none <80 148/85 144/81

CVD 51%

MI 50%

Stroke 30% (ns)

CV death 67%

UKPDS 1,148 8.4 <150 <85 154/87 144/82

DM-related 34%

deaths 32%

Stroke 44%

Microvasc 37%

ABCD 470 5.3 none <75 138/86 132/78

Renal (1º) nc

Microvasc nc

Death 49%

CVD ns

ACCORD BP Trial: Systolic BP (mean ± 95% CI)

Average after 1st year: 133.5 Standard vs. 119.3 Intensive, Delta = 14.2

Mean # Meds

Intensive: 3.2 3.4 3.5 3.4

Standard: 1.9 2.1 2.2 2.3

N Engl J Med. 2010;362:1575-85

DBP for the same time interval averaged 70 & 64 mm Hg

(Delta = 6 mm Hg)

N = 4,733

RZ: SBP <120 vs <140

Intensive

Events (%/yr)

Standard

Events (%/yr) HR (95% CI) P

Primary 208 (1.87) 237 (2.09) 0.88 (0.73-1.06) 0.20

Total Mortality 150 (1.28) 144 (1.19) 1.07 (0.85-1.35) 0.55

Cardiovascular Deaths 60 (0.52) 58 (0.49) 1.06 (0.74-1.52) 0.74

Nonfatal MI 126 (1.13) 146 (1.28) 0.87 (0.68-1.10) 0.25

Nonfatal Stroke 34 (0.30) 55 (0.47) 0.63 (0.41-0.96) 0.03

Total Stroke 36 (0.32) 62 (0.53) 0.59 (0.39-0.89) 0.01

Also examined Fatal/Nonfatal HF (HR=0.94, p=0.67), a composite of fatal coronary events, nonfatal MI

and unstable angina (HR=0.94, p=0.50) and a composite of the primary outcome, revascularization and

unstable angina

(HR=0.95, p=0.40)

N Engl J Med. 2010;362:1575-85

ACCORD: Primary Outcome by Pre-defined Subgroups

Also examined DBP tertiles (p=0.70) and number of screening meds

(p=0.44)

Int Gly

Std Gly

0

2

4

6

8

10

Std BP

Int BP

6.1 6.5

9.2

6.9

Derived from Margolis, et al.Diabetes Care 2014;37:1721–1728

*

* Std Gly/Std BP significantly higher CVD

event rate than other 3 groups

Outcomes Data from SPRINT and ACCORD BP Trials and Combined Data from Both Trials

Perkovic & Rodgers. N Engl J Med. 2015;373:2175-8SPRINT: N=9,3613.26 years

ACCORD BP: N=4,7334.7 years

© U N I V E R S I T Y O F U T A H H E A L T H , 2 0 1 7

SPRINT: Benefits of Intensive Treatment Are

Similar in Prediabetes and Normoglycemia

Normoglycemia (n=5,425, 58%)

(Serum glucose <100 mg/dL)

Interaction

P= 0.30

Primary Outcome

Bress AP. Diabetes Care. 2017

YearsYears

Prediabetes (n=3,898, 42%)

(Serum glucose ≥100 mg/dL)

© U N I V E R S I T Y O F U T A H H E A L T H , 2 0 1 7

…WITH NO ATTENUATION OF EFFECT AT HIGHER

SERUM GLUCOSE LEVELS

Hazard ratios and 95%CIs for major CVD associated with more intensive reductions in SBP

Bundy JD, et al. JAMA Cardiol. 2017;2:775-81

42 trials, n=144,220 Most of the trials included significant numbers of participants with diabetes mellitus

BLOOD PRESSURE TARGETS

ADA Position Statement 2017:Diabetes and Hypertension

Recommendations

• Most patients with diabetes and hypertension should be treated to a SBP goal <140 mm Hg and a DBP goal <90 mm Hg. A

• Lower SBP and DBP targets, such as <130/80 mm Hg, may be appropriate for individuals at high risk of CVD if they can be achieved without undue treatment burden. B

Diabetes Care 8/22/2017

• Strict interpretation of RCTs supports BP goal of <150/85 mm Hg.

• Achieved SBP in ADVANCE and the standard group in ACCORD BP

suggest SBP goal <140 mm Hg (JNC 8 and most other current guidelines

recommend this).

• The totality of evidence, including meta-analyses, suggests that a

target BP goal <130/80-85 mm Hg is reasonable in most diabetic

patients.

• ACCORD benefit in the Standard Glycemia subgroup and SPRINT benefit

in other high-risk groups support SBP goal <120 mm Hg.

Benefits of Antihypertensive

Medications

• Blood pressure reduction is paramount,

but not sufficient:

–antihypertensive drugs/classes matter!

–doses of drugs matter!

Relative Risk and 95% Confidence Intervals

Final Outcomes ResultsDoxazosin vs. Chlorthalidone

Favors Doxazosin Favors Chlorthalidone

0.50 1 2 3

CHD

All-Cause Mortality

Combined CHD

Stroke

Heart Failure

Combined CVD, p< 0.0001 1.20 (1.13 - 1.27)

1.80 (1.61 - 2.02)

1.26 (1.10 - 1.46)

1.07 (0.99 - 1.16)

1.03 (0.94 - 1.13)

1.03 (0.92 - 1.15)

Hypertension 2003;42:239-246

ALLHAT

Thiazide-type Diuretic Doses in Hypertension Morbidity Trials Showing MACE Reduction

Trial Drug Target Dose of

Thiazide (mg/d)

VA CSP M&M HCTZ 100

HDFP chlorthalidone 100

MRC I bendroflumethiazide 10

EWPHE HCTZ/triamterine 50

MRC Elderly HCTZ/amiloride 50

SHEP chlorthalidone 25

HYVET indapamide SR 1.5

ACCOMPLISH: Design

Jamerson KA et al. Am J Hypertens. 2003;16(part2)193A

*Beta blockers; alpha blockers; clonidine; (loop diuretics).

14 Days Day 1 Month 1 Month 2 Year 5

Screening

Amlodipine 5 mg +benazepril 20 mg

Ra

nd

om

iza

tio

n

Benazepril 40 mg + HCTZ 12.5 mg

Benazepril 40 mg + HCTZ 25 mg

Free add-on antihypertensive agents*

Month 3

Free add-on antihypertensive agents*

Amlodipine 5 mg +benazepril 40 mg

Amlodipine 10 +benazepril 40 mg

Benazepril 20 mg + HCTZ 12.5 mg

Titrated to achieve BP<140/90 mmHg; <130/80 mmHg in

patients with diabetes or renal insufficiency

Jamerson KA et al., NEJM 2008;359:2417-2428

ACCOMPLISH Results:Primary and Secondary End Points

HOPE-3 BP Intervention:Candesartan 16 mg/d + HCTZ 12.5 mg/d vs PBO

Lonn EM, et al. N Engl J Med. Published online 4/2/16

BP lowering for prevention of CVD and death: A systematic review and meta-analysis

Effects of reductions in SBP stratified by class of BP lowering drug

Ettehad D, Emdin CA, Kiran A, Anderson SG, Callender T, Emberson J, Chalmers J, Rodgers A, Rahimi K.Lancet. 2016 Mar 5;387:957-67.

Ettehad D, Emdin CA, Kiran A, Anderson SG, Callender T, Emberson J, Chalmers J, Rodgers A, Rahimi K.Lancet. 2016 Mar 5;387:957-67.

BP lowering for prevention of CVD and death: A systematic review and meta-analysis

Effects of reductions in SBP stratified by class of BP lowering drug

No significant differences in any CV outcomes or death

CAS

(n=11,267)

NCAS

(n=11,309)

No. (%)

Rate per

1,000 patient years

No. (%)Rate per 1,000 patient years

First event 1,119 (9.93) 36 1,150 (10.17) 37

Death 873 (7.75) 28 893 (7.90) 29

Nonfatal MI 151 (1.34) 5 153 (1.35) 5

Nonfatal stroke 131 (1.16) 4 148 (1.31) 5

Cardiovascular death 431 (3.83) 14 431 (3.81) 14

Cardiovascular hospitalization

726 (6.44) 24 709 (6.27) 23

INVEST: Verapamil vs AtenololAll participants had HTN + CAD

Pepine CJ, et al. JAMA. 2003;290:2805-2816

CAS = Calcium Antagonist Strategy; NCAS = Non-Calcium Antagonist Strategy

Time to Primary OutcomeONTARGET

Years of Follow-up

Cum

ulat

ive

Haz

ard

Rat

es

TelmisartanRamipril

0.0

0.05

0.10

0.15

0.20

0.25

0 1 2 3 4

TelmisartanRamipril

# at Risk Yr 1 Yr 2 Yr 3 Yr 4

T 8542 8176 7778 7420 7051

R 8576 8214 7832 7473 7095

Primary outcome: RR (CI): 1.01 (0.94-1.09)

(CV Death, MI, Stroke, CHF Hosp)

69% had HTN at baseline

53

Major OutcomesRelative Risks and 95% Confidence Intervals

Amlodipine/Chlorthalidone

0.50 1 2

ESRD 1.12 (0.89-1.40)

Heart Failure 1.38 (1.25-1.52)

Combined CVD 1.04 (0.99-1.09)

Stroke 0.93 (0.82-1.06)

All-Cause Mortality 0.96 (0.89-1.02)

CHD 0.98 (0.90-1.07)

Favors Favors

Amlodipine Chlorthalidone

Lisinopril/Chlorthalidone

0.50 1 2

1.11 (0.88-1.38)

1.19 (1.07-1.31)

1.10 (1.05-1.16)

1.15 (1.02-1.30)

1.00 (0.94-1.08)

0.99 (0.91-1.08)

Favors Favors

Lisinopril Chlorthalidone

ALLHAT

JAMA 2002;288:2981-2997

1.29 (0.94 - 1.75)ESRD

1.32 (1.11 - 1.58)Heart Failure

1.40 (1.17 - 1.68)Stroke

1.19 (1.09 - 1.30)Combined CVD

1.06 (0.95 - 1.18)Mortality

1.10 (0.94 - 1.28)CHD

Favors Favors

Lisinopril Chlorthalidone

0.50 1 2

0.93 (0.67 - 1.30)

1.15 (1.01 - 1.30)

1.00 (0.85 - 1.17)

1.06 (1.00 - 1.13)

0.97 (0.89 - 1.06)

0.94 (0.85 - 1.05)

0.50 1 2

Only Subgroup Differences:Lisinopril vs Chlorthalidone in

Blacks/Non-Blacks for CVD & Stroke

Blacks Non-Blacks

Favors Favors

Lisinopril Chlorthalidone

ALLHAT

26

49

66

0

20

40

60

80

1 1 or 2 Any

Number of Prescribed Drugs

Perc

ent

ALLHATCumulative Percent Controlled

(BP <140/90 mm Hg) at Five Years

Derived from Cushman et al. J Clin Hypertens. 2002;4:393-404.

Initial Choices of Medications

Diuretics

ACE inhibitors

or

ARBs*

Calcium

antagonists

* Recommended for CKD

Combining ACEI with ARB discouraged

b-blockers should be included in the regimen if there is a compelling indication for a

b-blocker

Diuretics or CCBs in Blacks

Primary Outcome: Home BPXXXXXXX

76

78

80

82

84

86

134

136

138

140

142

144

146

148

150

B P S D B 11Baseline Placebo Spironolactone

p<0.001

Doxazosin Bisoprolol

p<0.001H

om

e B

P (

mm

Hg)

Dia

sto

licS

ysto

lic

Double blind, Randomised, Placebo-Controlled, Cross-over Study

50 mg/d 8 mg/d 10 mg/d

Thank you!