Blood Pressure Management - Wright - Peninsula...• Wright JT Jr et al. NEJM 2015; 373: 2103-2116...
Transcript of Blood Pressure Management - Wright - Peninsula...• Wright JT Jr et al. NEJM 2015; 373: 2103-2116...
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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 - - - - - +
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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.
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