3. Systolic Blood Pressure Intervention Trial (SPRINT)
Principal Results
Paul K. Whelton, MB, MD, MSc
Chair, SPRINT Steering Committee
Tulane University School of Public Health and Tropical Medicine, and School of Medicine
For the SPRINT Research Group
N Engl J Med. 2015 Nov 26;373(22):2103-16.
4. SPRINT Research Question
Examine effect of more intensive high blood pressure treatment
than is currently recommended
Randomized Controlled Trial
Target Systolic BP
Intensive Treatment
Goal SBP < 120 mm Hg
Standard Treatment
Goal SBP < 140 mm Hg
SPRINT design details available at:
• ClinicalTrials.gov (NCT01206062)
• Ambrosius WT et al. Clin. Trials. 2014;11:532-546.
5. Major Inclusion Criteria
• ≥50 years old
• 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 – <60 ml/min/1.73m2
• Framingham Risk Score for 10-year CVD risk ≥ 15%
• Age ≥ 75 years
At least one
6. 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
9. ACCORD in The Diabetics
N Engl J Med. 2010 Apr 29;362(17):1575-85.
10. Eur Heart J. 2017 Apr 14;38(15):1132-1143.
*SBP at baseline
11. J Am Coll Cardiol. 2020 Apr 14;75(14):1644-1656.
PARAGON-HF
Baseline and mean achieved
SBP of 120 to 129 mm Hg
identified the lowest risk
patients with HFpEF.
12. Pre-specified Subgroups of Special Interest
• Age (<75 vs. ≥75 years)
• Gender (Men vs. Women)
• Race/ethnicity (African-American vs. Non African-American)
• CKD (eGFR <60 vs. ≥60 mL/min/1.73m2)
• CVD (CVD vs. no prior CVD)
• Level of BP (Baseline SBP tertiles: ≤132, 133 to 144, ≥145 mm Hg)-
13. Systolic BP During Follow-up
Mean SBP
136.2 mm Hg
Mean SBP
121.4 mm Hg
Average SBP
(During Follow-up)
Standard: 134.6 mm Hg
Intensive: 121.5 mm Hg
Average number of
antihypertensive
medications
Number of
participants
Standard
Intensive
Year 1
14. Number of
Participants
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
Cumulative Hazard
(319 events)
15. SPRINT Primary Outcome and its Components
Event Rates and Hazard Ratios
Intensive Standard
No. of Events Rate, %/year No. of Events Rate, %/year HR (95% CI) P value
Primary Outcome 243 1.65 319 2.19 0.75 (0.64, 0.89) <0.001
All MI 97 0.65 116 0.78 0.83 (0.64, 1.09) 0.19
Non-MI ACS 40 0.27 40 0.27 1.00 (0.64, 1.55) 0.99
All Stroke 62 0.41 70 0.47 0.89 (0.63, 1.25) 0.50
All HF 62 0.41 100 0.67 0.62 (0.45, 0.84) 0.002
CVD Death 37 0.25 65 0.43 0.57 (0.38, 0.85) 0.005
16. Primary Outcome Experience in the Six Pre-specified Subgroups of Interest
*Treatment by subgroup interaction
17. Intensive Standard
Events %/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) 0.27
Kidney transplant 0 - 0 - - .
Secondary CKD Outcome
Incident 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) <.0001
Incident albuminuria** 110 2.00 135 2.41 0.81 (0.63, 1.04) 0.10
Renal Disease Outcomes
*Confirmed on a second occasion ≥90 days apart **Doubling of urinary albumin/creatinine ratio from <10 to >10 mg/g
28. 28
Sci Rep. 2019 Sep 10;9(1):13070.
*Occurrence of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute
decompensated heart failure or death from cardiovascular causes.
29. 2017 BP Thresholds for and Goals of Pharmacological Therapy in
Patients With Hypertension According to Clinical Conditions
Clinical Condition(s)
BP
Threshold,
mm Hg
BP Goal,
mm Hg
General
Clinical CVD or 10-year ASCVD risk ≥10% ≥130/80 <130/80
No clinical CVD and 10-year ASCVD risk <10% ≥140/90 <130/80
Older persons (≥65 years of age; noninstitutionalized,
ambulatory, community-living adults)
≥130 (SBP) <130 (SBP)
Specific comorbidities
Diabetes mellitus ≥130/80 <130/80
Chronic kidney disease ≥130/80 <130/80
Chronic kidney disease after renal transplantation ≥130/80 <130/80
Heart failure ≥130/80 <130/80
Stable ischemic heart disease ≥130/80 <130/80
Secondary stroke prevention ≥140/90 <130/80
Secondary stroke prevention (lacunar) ≥130/80 <130/80
Peripheral arterial disease ≥130/80 <130/80
ASCVD indicates atherosclerotic cardiovascular
disease; BP, blood pressure; CVD, cardiovascular
disease; and SBP, systolic blood pressure.
46. Comparison of four BP measurement methods
Clinical characteristics
Feasibility
In Taiwan
(routine use)
Variability
(routine use)
ROBP YES HIGH
AOBP NO LOW
HBPM YES LOW
ABPM NO LOW
46
Slides courtesy of CE Chiang
47. Home BP Monitoring
•Guideline recommended
•Improves diagnostic precision
- identifies white coat and masked hypertension
•Better patient engagement in care process
•Better prediction of HMOD versus office BP and
increasing evidence of better prediction of outcomes
47
48. Reliability of Office, Home, and Ambulatory BP
measurements and correlation with LV Mass
Schwartz, J.E. et al. J Am Coll Cardiol. 2020;76(25):2911–22.
IDH study
52. Why is HBP more associated with Risk than OBP?
• OBP is often poorly performed
• Better characterization of blood pressure in a more natural
environment
• Multiple measurement improves precision
52
56. Method to obtain reliable HBP estimates
56
"722"
principle
Timing of HBP monitoring
"7" 7 (at least 4) consecutive days
"2"
2 times per day: in the morning (taken within 1 hour after
awakening, after voiding, and before taking food and
medications) and in the evening (within 1 hour before
bedtime)
"2"
2 or more BP readings, 1 minute apart, taken per occasion
(≥3 BP readings if atrial fibrillation)
58. The “722” principle for home BP monitoring
58
Settings in the clinic Frequency of HBP monitoring with the “722” principle
Hypertension
(≥140/90 mmHg)
Treatment-naïve
One “722” cycle, for confirmation of diagnosis and
phenotype identification
Initiation of drug therapy
2 weeks later, then every 1 month if uncontrolled, or
every 3 months if under control
Adjustment of drug therapy
2 weeks later, then every 1 month if uncontrolled, or
every 3 months if under control
Treated but uncontrolled Every 1 month
Treated and controlled Every 3 months
59. Comparison of four BP measurement methods
Clinical characteristics Outcome study
Feasibility
In Taiwan
(routine use)
Variability
(routine use)
Observational
BP target-
driven trials
ROBP YES HIGH YES YES
AOBP NO LOW YES YES/SPRINT
HBPM YES LOW YES YES/STEP
ABPM NO LOW YES NO
59
Slides courtesy of CE Chiang
60. STEP
• Prospective, multi-center, randomized controlled trial
• 9624 patients screened from 42 clinical centers in China
Intensive treatment:
110 mm Hg ≤SBP<130 mm Hg (n=4243)
Standard treatment:
130 mm Hg ≤SBP<150 mm Hg (n=4268)
Screen
Randomization
0
-2w 1m 3m 15m
9m 48m
6m 12m 18m …
Follow-up
visits
1 2 3 4 5 6 7 8 18
…
2m
60
N Engl J Med. 2021 Sep 30;385(14):1268-1279.
61. Inclusion & Exclusion Criteria
Inclusion criteria
1. Systolic blood pressure (SBP) between 140190 mm Hg in the three screening visits or currently under anti-hypertension treatment.
2. An age of 6080 years, Han ethnicity.
3. Signed the written informed consent.
1. History of large atherosclerotic cerebral infarction or
hemorrhagic stroke.
2. Diagnosed secondary hypertension.
3. Hospitalization for myocardial infarction (MI) within the last 6
months.
4. Coronary revascularization within the last 12 months.
5. Planned to perform PCI or CABG in the next 12 months.
6. History of sustained atrial fibrillation.
Exclusion criteria
7. III-IV heart failure.
8. Severe valvular.
9. Hypertrophic cardiomyopathy
10. Uncontrolled diabetes mellitus
11. Severe liver or kidney dysfunction
12. Severe somatic disease such as cancer.
13. Severe cognitive impairment or mental disorders.
14. Participating in other clinical trials.
61
62. Intervention
Blood Pressure Monitoring
Office blood pressure measurements:
• By a trained physician or nurse
• Using validated Omron BP monitor
• Participants were required to rest for at
least 5 minutes
• Measured three times with 1-minute
intervals
Home blood pressure monitoring:
• The smartphone-based App was used
• Upload the readings to data recording
center, at least 1 day per week during
follow-up
Medications
• Olmesartan
• Amlodipine
• Hydrochlorothiazide
Examinations
• Demographic data;
• Anthropometrics;
• Laboratory exams;
• Electrocardiography;
• Echocardiography;
• Ankle-brachial index;
• Brachial-ankle PWV;
• Cognitive function;
• Medication adherence.
62
65. Time after randomization (Months)
Cumulative
incidence
26%
Results- Primary Composite Outcome
Standard
treatment
4268 4147 4070 4000 3938 3849 3664 1200
Intensive
treatment
4243 4174 4109 4039 3970 3867 3694 1234
NO.at risk
The cardiovascular
benefits
65
147 of 4243 patients (3.5% [1.0% per
year]) in the intensive-treatment group;
196 of 4268 patients (4.6% [1.4% per
year]) in the standard-treatment group.
During the median follow-up period of
3.34 years, primary-outcome events
occurred in:
66. Results- Secondary Outcomes
B. Acute coronary syndrome C. Heart failure
A. Stroke
33%
E. Mortality from CV causes
D. Major adverse cardiac events F. Others
The risks of
Coronary revascularization
Atrial fibrillation
All-cause mortality
were not different between groups
33% 73%
28% 28%
66
68. HBPM-based universal BP target for pharmacological management
* Threshold: ≥140/90 mmHg for initiation of pharmacological treatment
† Target: <120/80 mmHg if tolerable
‡ Risk factors include advanced age (≥65 years), male sex, dyslipidemia, smoking, family history of premature
ASCVD (onset <50 years of age), and gestational hypertension or preeclampsia with adverse pregnancy outcomes
Low risk Intermediate risk High risk Very high risk
Home BP targets
(mmHg)
Elevated BP
SBP 120-129
DBP <80
Grade 1
SBP 130-139
DBP 80-89
Grade 2
SBP ≥140
DBP ≥90
Stage 1
Risk factors‡
n <3 <130/80 <130/80* <130/80*
n ≥3 <130/80 <130/80 <130/80
Stage 2
DM, CKD 3, or HMOD
<130/80 <130/80 <130/80
Stage 3
ASCVD or CKD ≥4 or
DM with organ damage
<130/80† <130/80† <130/80†
69.
70. 70
Effects of reduced-sodium, added-potassium salt substitute
on stroke – the salt substitute and stroke study (SSaSS)
Professor Bruce Neal
Effects of reduced-sodium, added-potassium salt substitute
on stroke – the salt substitute and stroke study (SSaSS)
Professor Bruce Neal
N Engl J Med. 2021 Sep 16;385(12):1067-1077.
71. Design
• Pragmatic, large-scale (n=20,995), open, cluster randomised trial
• Salt substitute (70%NaCl, 30%KCl) versus regular salt (100%NaCl)
Recruitment and
baseline data
(in person)
Randomisation
6-monthly follow-up for all
(routinely collected health data and in-person years 0, 1, 2 and 5)
Annual in-person measurement of blood pressure and urinary electrolytes in a
subset of 54 to 140 villages
300 villages (n=10504) salt substitute
300 villages (n=10491) regular salt
72. Follow-up and intermediate outcomes
Follow-up
• Mean follow-up 4.74 years
• 100% vital status for all participants
• 99.9% complete follow-up for non-fatal outcomes
• At 5 years, 92% intervention group still using salt substitute and 6% control group
started using salt substitute
Average effects of salt substitute versus regular salt
• Systolic BP -3.3 (95%CI -4.5 to -2.2) mmHg
• Diastolic BP -0.7 (95%CI -1.4 to 0.05) mmHg
• 24-hour urinary sodium -15 (95%CI -24 to -6.7) mmol
• 24-hour urinary potassium 20 (95%CI 18 to 23) mmol
76. Hyperkalemia
76
• Participants with event = 315
• Rate ratio = 1.04 (0.80 to 1.37)
• P value = 0.76
Sudden vascular death
• Rate ratio = 0.94 (0.82 to 1.07)
77. 1 drug or SPC*
if <20/10 mmHg
above BP target
2 drugs or SPC
if ≥20/10 mmHg
above BP target
Wang TD, 2022.
H: HBPM confirmation based on the 722 protocol
E: Exacerbator/Inducer/Secondary causes
R: Risk chart-based assessment
2022 Taiwan
Hypertension Guidelines
Assessment Flowchart
* Consider half tablet in frailer patients
HER