The document summarizes the results of the SPRINT trial, which compared an intensive blood pressure treatment target of less than 120 mmHg systolic to a standard target of less than 140 mmHg. Key findings include: - The intensive treatment group had a significantly lower rate of the primary composite outcome of myocardial infarction, other acute coronary syndromes, stroke, heart failure or death from cardiovascular causes. - Benefits of intensive treatment were seen across most pre-specified subgroups including those with and without chronic kidney disease. - Intensive treatment led to more frequent adverse events related to low blood pressure like hypotension, but no differences in falls or fractures. - More medications were required to achieve the lower blood

1. 2023 Updated Hypertension Guideline
高雄醫學大學 附設中和紀念醫院
心臟血管內科
林宗憲
Conflict of Interest: nil

2. Journal of the Chinese Medical Association 2015;78:1-47

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

7. Lancet. 2013 Aug 10;382(9891):507-15

8. Lancet. 2013 Aug 10;382(9891):507-15
1 Endpoint

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

18. Kidney Int. 2021 Mar;99(3S):S1-S87.

20. SPRINT vs. SPRINT-SENIOR
JAMA. 2016;315(24):2673-2682.
Slides courtesy of CE Chiang

21. JAMA. 2016 Jun 28;315(24):2673-82

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

23. Hypertension. 2020 Mar;75(3):660-667.

24. Number (%) of Participants with a
Monitored Clinical Measure During Follow-up
Number (%) 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 with 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 months
2. Drop in SBP ≥20 mmHg or DBP ≥10 mmHg 1 minute after standing (measured at 1, 6, and 12 months and yearly thereafter)

25. Arch Intern Med. 2012 Aug 13;172(15):1162-8.
2340 persons  65 years

26. 26
Lancet. 2021 Sep 18;398(10305):1053-1064.

27. 27
Lancet. 2021 Sep 18;398(10305):1053-1064.

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.

30. Hypertension. 2016 May;67(5):808-12

31. Acta Cardiol Sin 2017;33:213-225

32. Acta Cardiol Sin. 2017 May;33(3):213-225.

33. Acta Cardiol Sin. 2017 May;33(3):213-225.

34. Hypertension. 2019 Feb;73(2):481-490.
SBP
AOBP = HBPM

35. Hypertension. 2019 Feb;73(2):481-490.
DBP
AOBP = HBPM

36. Hypertension. 2019 Feb;73(2):481-490.
SBP
AOBP = DT_ABPM

37. Hypertension. 2019 Feb;73(2):481-490.
DBP
AOBP = DT_ABPM

38. AOBP = HBPM = DT_ABPM

39. 39
Clinic HBPM Daytime
ABPM
Nighttime
ABPM
24-Hour
ABPM
120/80 120/80 120/80 100/65 115/75
130/80 130/80 130/80 110/65 125/75
140/90 135/85 135/85 120/70 130/80
160/100 145/90 145/90 140/85 145/90
Corresponding Values of SBP/DBP for Clinic, HBPM,
Daytime, Nighttime, and 24-Hour ABPM Measurements
Whelton PK. Hypertension. 2018;71:e13.
Vongpatanasin W. Hypertension. 2018;72:1312.
Dallas Heart Study (n=5768)
North Carolina Masked Hypertension (n=420)
Home
ACC/AHA

40. Corresponding values between OBP, HBP, ABP
OBP HBPM/AOBP ABPM
Daytime 24-hr Nighttime
120/80 120/80 120/80 115/75 100/65
130/80 130/80 130/80 125/75 110/65
140/90 135/85 135/85 130/80 120/70
160/100 145/90 145/90 145/90 140/85
40
Hypertension. 2018;71:e13-e115.
Slides courtesy of CE Chiang

41. Slides courtesy of CE Chiang

42. 42
Lancet. 2021 May 1;397(10285):1625-1636.

43. 43
SBP at baseline

44. 44
5 mm Hg systolic blood pressure reduction

45. Why Select HBPM?
45

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

49. 49
J Hum Hypertens. 2005 Oct;19(10):801-7.

50. 50
Circulation. 2005 Apr 12;111(14):1777-83

51. 51
Hypertension. 2010 Jun;55(6):1346-51.

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

53. Hypertension. 2019 Feb;73(2):481-490.

54. 54
Blood Press Monit. 2006 Apr;11(2):59-62.

55. 55
J Hypertens. 1998 Jul;16(7):971-5.

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)

57. Methods to perform HBP monitoring correctly

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 140190 mm Hg in the three screening visits or currently under anti-hypertension treatment.
2. An age of 6080 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

63. Endpoints
Primary outcome
A composite of :
• Stroke;
• Acute coronary Syndrome
(myocardial infarction and hospitalized unstable angina);
• Acute decompensated heart failure;
• Coronary revascularization;
• Atrial fibrillation;
• Mortality from cardiovascular causes.
Secondary outcomes
• Component of primary outcome;
• All-cause Mortality;
• Major adverse cardiac events;
• Renal outcomes;
• Cognitive function;
• Atrial stiffness;
• New-onset Diabetes.
63

64. Medications
VISIT_12M VISIT_24M VISIT_36M VISIT_42M
Intensive
(n=4172)
Standard
(n=4158)
Intensive
(n=4130)
Standard
(n=4131)
Intensive
(n=4085)
Standard
(n=4086)
Intensive
(n=2593)
Standard
(n=2592)
Patients using antihypertensive agent
CCB alone
780
(18.7%)
1209
(29.1%)
624
(15.1%)
1088
(26.3%)
532
(13.0%)
1028
(25.2%)
281
(10.8%)
531
(20.5%)
ARB alone
486
(11.6%)
726
(17.5%)
431
(10.4%)
726
(17.6%)
357 (8.7)
621
(15.2%)
184 (7.1%)
329
(12.7%)
CCB + ARB
1945
(46.6%)
1569
(37.7%)
2031
(49.2%)
1617
(39.1%)
2090
(51.2%)
1636
(40.0%)
1086
(41.9%)
787
(30.4%)
Hydrochlorothiazide 0 (0%) 3 (0.1%) 0 (0%) 1 (0.0%) 0 (0.0%) 1 (0.0%) 0 (0%) 0 (0%)
CCB +
Hydrochlorothiazide
18 (0.4%) 19 (0.5%) 37 (0.9%) 11 (0.3%) 22 (0.5%) 6 (0.1%) 23 (0.9%) 8 (0.3%)
ARB +
Hydrochlorothiazide
28 (0.7%) 21 (0.5%) 25 (0.6%) 24 (0.6%) 30 (0.7%) 27 (0.7%) 17 (0.7%) 7 (0.3%)
ARB+CCB+
Hydrochlorothiazide
448
(10.7%)
172
(4.1%)
527
(12.8%)
174
(4.2%)
524
(12.8%)
185
(4.5%)
240
(9.3%)
87
(3.4%)
Other drugs
337
(8.1%)
258
(6.2%)
328
(7.9%)
265
(6.4%)
412
(10.1%)
347
(8.5%)
711
(27.4%)
759
(29.3%)
Number of agents, no. (%)
0
130
(3.1%)
181
(4.4%)
127
(3.1%)
225
(5.4%)
118
(2.9%)
235
(5.8%)
51
(2.0%)
84
(3.2%)
1
1266
(30.3%)
1938
(46.6%)
1055
(25.5%)
1815
(43.9%)
889
(21.8%)
1650
(40.4%)
465
(17.9%)
860
(33.2%)
2
1991
(47.7%)
1609
(38.7%)
2093
(50.7%)
1652
(40.0%)
2142
(52.4%)
1669
(40.8%)
1126
(43.4%)
802
(30.9%)
3
448
(10.7%)
172
(4.1%)
527
(12.8%)
174
(4.2%)
524
(12.8%)
185
(4.5%)
240
(9.3%)
87
(3.4%)
Results - Blood Pressure & Medications
Standard
treatment
4268 4147 4070 4000 3938 3849 3664 1200
Intensive
treatment
4243 4174 4109 4039 3970 3867 3694 1234
Standard
treatment
1.4 1.5 1.5 1.5 1.5 1.5 1.5 1.5
Intensive
treatment
1.5 1.7 1.8 1.8 1.9 1.9 1.9 1.9
SBP
Months
Systolic
blood
pressure
(mm
Hg)
Mean SBP
Intensive-treatment group: 126.7 mm Hg;
Standard-treatment group: 135.9 mm Hg
Between-group difference: 9.2 mm Hg
64

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

67. 67

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†

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

73. Stroke
• Participants with event = 2678
• Rate ratio = 0.86 (0.77 to 0.96)
• P value = 0.006

74. Major adverse cardiovascular events
• Participants with event = 4499
• Rate ratio = 0.87 (0.80 to 0.94)
• P value <0.001

75. Total mortality
75
• Participants with event = 4172
• Rate ratio = 0.88 (0.82 to 0.95)
• P value <0.001

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

78. Slides courtesy of TD Wang

82. Hypertension. 2021 Feb;77(2):692-705.

83. Hypertension. 2021 Feb;77(2):692-705.
SBP

84. Hypertension. 2021 Feb;77(2):692-705.
DBP

86. Circulation. 2019 Jul 23;140(4):303-315
132 non-obese, older patients with well-controlled blood glucose

87. Take Home Messages
• Blood pressure universal goals
- < 130/80 mmHg
• From office to home blood pressure
- better prognostic & feasible
• Non-pharmacological treatment
- SABCED & salt substitute
• Pharmacological treatment
- ABCD, MRA, -blocker, ARNI, SGLT2i
- Single pill combination

88. 謝謝聆聽 敬請指教