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February 16, 2011 1

Emeritus Professor of MedicineEmeritus Director, Clinical Hypertension Program

and the William T Dahms MD Clinical Research UnitClinical and Translational Science Collaborative

BLOOD PRESSURE CONTROL IN PATIENTS WITH HYPERTENSION

Jackson T. Wright, Jr., MD, PhD, FACP, FASH

Pharmacologic Treatment of Hypertension in Adults Aged 60 Years or Older to Higher Versus Lower Blood Pressure Targets: A Clinical Practice Guideline From the American College of Physicians and the 

American Academy of Family PhysiciansOnline: Ann Intern Med. doi:10.7326/M16‐1785

Recommendation 1: ACP and AAFP recommend that clinicians initiate treatment in adults aged 60 years or older with systolic blood pressure persistently at or above 150 mm Hg to achieve a target systolic blood

pressure of less than 150 mm Hg to reduce the risk for mortality, stroke, and cardiac events. (Grade: strong

recommendation, high-quality evidence).

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Ann Intern Med 2014;160: 499-504

US CVD Death Rates for Individuals Less than and Older than 65 years

Condition (Cause of death by underlying Cause)

Age < 65 or

≥ 65 years

1989-1998 Yearly

Average Death Rate per 100,000

1999-2010 Yearly

Average Death Rate per 100,000

1989-1998 Average annual % change in

age-adjusted death rates (AAPC (%))

1999-2010 Average annual % change in

age-adjusted death rates (AAPC (%))

CHD < 65 36 30 -3.6 -3.4

CHD ≥ 65 1319 1038 -2.7 -5.6

Stroke < 65 9 7 -1.3 -2.3

Stroke ≥ 65 436 356 -0.9 -5.3

Age-Adjusted to the 2000 U.S. Standard Population - Analysis from CDC Wonder byDr. Micheal Musslino, NHLBI, Epidemiology Branch.

Wright JT Jr, et al. Ann Intern Med 2014;160: 499-504

Complex Hypertension Increases Mortality Risk

Kannel WB. Am J Hypertens. 2000;13:3S-10S.

10-Y

ear

Prob

abili

tyof

Eve

nt (%

)

4 610

14

21

40

06

121824303642

1st Qtr 2nd Qtr 3rd Qtr 4th QtrSBP 150-160 + + + + + +Cholesterol 240-262 - + + + + +HDL-C 33-35 - - + + + +Diabetes - - - + + +Cigarettes - - - - + +ECG-LVH - - - - - +

14

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125

130

135

140

145

2000 2002 2004 2006 2008 2010

Age Adjusted SBP in Adults 60 + Yrs. 1999 to 2010 NHANES Guo et al.

2012 JACC

Another Contributor with a Different Secular Pattern

10 mm DeltaNo Change

1988 to 1999

Wright JT Jr, et al; Annals Intern Med 2014:Online

Figure 1.    Prevalence of High Blood Pressure In Adults by Age and Sex (NHANES 2005‐2006)

AronowWS et al. JACC 2011;57:2037‐2114)

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TRIALS COMPARING SBP THRESHOLDS

Trial (Reference)

Participants (N)

Duration(Yrs)

Total End Points

(N)PrimaryOutcome

Coronary Heart

DiseaseComposite

CVDStrokes Heart

Failure

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Major Exclusion Criteria

• Stroke

• Diabetes mellitus

• Polycystic kidney disease

• Congestive heart failure (symptoms or EF < 35%)

• Proteinuria >1g/d

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

• Adherence concerns

BP Intervention• BP monitored monthly for 3 months and every 3 months thereafter

(additional visits could be scheduled)

• Antihypertensive medication titration decisions based on mean BP(3 readings at each visit), using a structured stepped-care approach

• Agents from all major antihypertensive drug classes available free of charge– While not mandated, investigators were encouraged to thiazide-type diuretics, calcium

channel blockers, and/or ACE inhibitors or ARBs (not both) before other agents added– Chlorthalidone and amlodipine were recommended agents in their class

• Periodic assessment for orthostatic hypotension and related symptoms

Chlorthalidone vs HCTZ Estimated Dosing Equivalence based on Estimated Equivalent BP Reduction

3.8 6.4 6.5

12

1820

18

2324 28

0

5

10

15

20

25

30

3 6 12.5 25 50 100 200

HCTZ Chlor.

Red

ucti

on in

SB

P (

mm

Hg)

Carter BL, Ernst ME, Cohen JD. Hypertension 2004;43:4-9.

50 mg HCTZ ~ 25 to 37.5 mg chlorthalidone

Current dosing of 12.5-25 mg can be viewed as compromise between antihypertensive efficacy and kaliuresis

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Demographic and Baseline CharacteristicsTotal

N=9361IntensiveN=4678

StandardN=4683

Mean (SD) age, years 67.9 (9.4) 67.9 (9.4) 67.9 (9.5)% ≥75 years 28.2% 28.2% 28.2%

Female, % 35.6% 36.0% 35.2%White, % 57.7% 57.7% 57.7%African‐American, % 29.9% 29.5% 30.4%Hispanic, % 10.5% 10.8% 10.3%Prior CVD, % 20.1% 20.1% 20.0%Mean 10‐year Framingham CVD risk, % 20.1% 20.1%  20.1%Taking antihypertensive meds, %  90.6% 90.8% 90.4%Mean (SD) number of antihypertensive meds 1.8 (1.0) 1.8 (1.0) 1.8 (1.0)Mean (SD) Baseline BP, mm HgSystolic 139.7 (15.6) 139.7 (15.8) 139.7 (15.4)Diastolic 78.1 (11.9) 78.2 (11.9) 78.0 (12.0)

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

Intensive: 121.5 mm Hg

Average number ofantihypertensivemedications

Number ofparticipants

Standard

Intensive

Year 1

SPRINT Primary Outcome and its ComponentsEvent Rates and Hazard Ratios

Intensive StandardNo.

of EventsRate,

%/yearNo. of Events

Rate, %/year

HR (95% CI)

P value

Primary Outcome 243 1.65 319 2.19 0.75 (0.64, 0.89)

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gPrimary Outcome Experience in the

Six Pre-specified Subgroups of Interest

*Treatment by subgroup interaction

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

Participants with CKD at Baseline

Primary CKD outcome 14 0.33 15 0.36 0.89 (0.42, 1.87) 0.76

≥50% reduction in eGFR* 10 0.23 11 0.26 0.87 (0.36, 2.07) 0.75

Dialysis 6 0.14 10 0.24 0.57 (0.19, 1.54) 0.27Kidney transplant 0 - 0 - - .

Secondary CKD OutcomeIncident albuminuria** 49 3.02 59 3.90 0.72 (0.48, 1.07) 0.11

Participants without CKD at Baseline

Secondary CKD outcomes

≥30% reduction in eGFR*

127 1.21 37 0.35 3.48 (2.44, 5.10)

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jamanetwork.com

Available at jama.com and on The JAMA Network Reader at

mobile.jamanetwork.com

JD Williamson and Coauthors for the SPRINT Research Group

Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged ≥75 Years: A Randomized Clinical Trial

Published May 19, 2016

Baseline Characteristics: Participants 75 years or older

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Values are N (%), mean ± SD, or median (IQR)

Baseline Characteristics: Participants 75 years or older

Values are N (%), mean ± SD, or median (IQR)

(MoCA) Montreal Cognitive Assessment (VR-12) Veteran’s RAND 12-item Health Survey

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# of Participants

# of classes of antihypertensive

meds

Standard-treatment134.8 mmHg

95% CI (134.3, 135.)

Intensive-treatment123.4 mmHg

95% CI (123.0, 123.9)

Systolic BP During Follow-up

Willamson JD, et al for the SPRINT Research Group 2016; JAMA (online)

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Delta = 11.3 mm Hg

Delta SBP: 11.4 mmHg (95% CI: 10.8 to 11.9 mmHg)

Kaplan-Meier Survival Curves for SPRINT Primary Outcome and All-Cause Mortality in Participants 75

and older

HR: 0.67 95% CI (0.51 to 0.86) HR: 0.68 95% CI (0.50 to 0.92)

NNT = 28 at 3.26 years NNT = 41 at 3.26 yearsWillamson JD, et al for the SPRINT Research

Group 2016; JAMA (online)

Kaplan-Meier Survival Curves 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

p for interaction (ns)

Willamson JD, et al for the

SPRINT Research

Group 2016; JAMA (online)

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Cumulative Hazards for SPRINT Primary Outcome by Gait Speed

Willamson JD, et al for the SPRINT Research Group 2016; JAMA (online)

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Serious Adverse Events* (SAE) During Follow-up

All SAE reports

Number (%) of ParticipantsIntensive Standard HR (P Value)

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

SAEs associated with Specific Conditions of InterestHypotension 110 (2.4) 66 (1.4) 1.67 (0.001)

Syncope 107 (2.3) 80 (1.7) 1.33 (0.05)

Injurious fall 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 (

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Serious Adverse Events, by treatment group in SPRINT participants > 75 years

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Conditions of Interest for Participants > 75 Years

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Cumulative Hazards for SPRINT Outcomes in Participants 75 and older

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Primary outcome includes non-fatal myocardial infarction (MI), acute coronary syndrome not resulting in MI, non-fatal stroke, non-fatal acute decompensated heart failure, and CVD death.

Primary Outcome All-Cause Mortality

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Cumulative Hazards for SPRINT Primary Outcome by Frailty Status

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Number of Participants with a Monitored Clinical Measure During Follow-up

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Intensive-treatment Standard-treatmentN with event (%) N with event (%) HR (95% CI) p-value

Monitored Clinical EventsLaboratory Measures

Sodium150 mmol/L 1 (0.1) 0 (0.0) - -Potassium5.5 mmol/L 69 (5.2) 65 (4.9) 1.01 (0.71, 1.42) 0.972

Signs and SymptomsOrthostatic hypotension 277 (21.0) 288 (21.8) 0.90 (0.76, 1.07) 0.241Orthostatic hypotension with dizziness 25 (1.9) 17 (1.3) 1.44 (0.77, 2.73) 0.252

Date of download: 2/13/2017 Copyright © 2017 American Medical Association. All rights reserved.

From: Effect of Intensive Blood Pressure Control on Gait Speed and Mobility Limitation in Adults 75 Years or OlderA Randomized Clinical Trial

JAMA Intern Med. Published online February 06, 2017. doi:10.1001/jamainternmed.2016.9104

Linear Mixed-Effect Model Estimates of Annual Change in Gait Speed by Treatment Group and for Subgroupsa

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Date of download: 2/13/2017 Copyright © 2017 American Medical Association. All rights reserved.

From: Effect of Intensive Blood Pressure Control on Gait Speed and Mobility Limitation in Adults 75 Years or OlderA Randomized Clinical Trial

JAMA Intern Med. Published online February 06, 2017. doi:10.1001/jamainternmed.2016.9104

Effect of Intensive vs Standard Treatment on Transition Probabilities for Multistate Model of Mobility Limitation Accounting for the Competing Risk of Deatha

Summary and Conclusions

• SPRINT now fills the deficit of RCT outcome data on SBP targets below 150 mmHg that led to a majority of a 2014 US guideline panel’s recommendation of a less than 150 treatment target in patients over age 60.

• SPRINT documented the benefit of a SBP target of < 120 mmHg over one < 140 on CV events (NNT= 61) and total mortality (NNT=90) even in patients over age 75 (NNT= 28 and 41 resp).

• SPRINT also established that even in those over age 75, frailty status in non-institutionalized patients did not lessen benefit, and the lower SBP target was at least as well tolerated as in the whole cohort

• Overall, benefits of more intensive BP lowering in SPRINT exceeded the potential for harm

• Interestingly, we now have substantially better risk/benefit data for recommending target BPs below 140 in those over age 60 than we have in those less than age 50.

THANK YOU