1. a cautionary note from SPRINT
Increased all-cause mortality with intensive blood-pressure control in patients with a baseline systolic blood pressure of ≥160 mmHg and a Lower Framingham risk score:
a cautionary note from SPRINT
Tzung-Dau Wang1, FESC, Hung-Ju Lin1, Wen-Jone Chen2, FESC,
Te-Chang Weng3, Wen-Yi Shau3
1. Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei City, Taiwan; 2. Department of Emergency Medicine, National Taiwan University Hospital, Taipei City, Taiwan; 3. Pfizer, Taipei, Taiwan

2. Potential conflicts of interest
Speaker‘s name: Tzung-Dau Wang
I do not have any potential conflict of interest

3. Greater BP reduction, smaller risk reduction!?
Background
SPRINT: Primary outcome
SPRINT: Death from any cause
J curve: vulnerability to absolute BP value or BP reduction?
Universal or individualized BP target?
Greater BP reduction, smaller risk reduction!?
N Engl J Med 2015;373:
Chiang CE, Wang TD, et al. Acta Cardiol Sin 2017;33:

4. Methods
Access to the patient-level data of SPRINT through National Heart, Lung, and Blood Institute BioLINCC data repository after approval from the Institutional Review Board at National Taiwan University Hospital
Outcomes: (1) Primary outcome (MI, non-MI ACS, stroke, acute decompensated HF, and CV death), (2) all-cause death, (3) primary outcome + all-cause death, and (4) non-CV death (all-cause death – CV death, including undetermined/not yet adjudicated cases)
Due to small sample size in subgroup analyses, HR estimated from Cox model assuming common baseline hazard across clinic site

5. Results: Step 1, more detailed subgroup analysis based on baseline
systolic BP stratified by clinically-oriented cut-off points
Primary outcome
All-cause death
HR (95% CI)
P for
trend
Systolic BP, mmHg
Overall
0.5
1.0
2.0
Intensive Better
Standard Better
0.75 ( )
Overall
0.5
1.0
2.0
Intensive Better
Standard Better
0.73 ( )
(n=9361)
<130
0.72 ( )
0.107
0.76 ( )
0.005
(n=2324)
≥130 to <140
0.63 ( )
≥130 to <140
0.61 ( )
(n=2640)
≥140 to <150
0.92 ( )
≥140 to <150
0.67 ( )
(n=2159)
≥150 to <160
0.74 ( )
≥150 to <160
0.69 ( )
(n=1262)
≥160
0.86 ( )
≥160
1.16 ( )
(n=976)

6. a baseline systolic BP of ≥160 mmHg versus <160 mmHg
Results: Step 2, safety concerns with intensive BP control for patients with
a baseline systolic BP of ≥160 mmHg versus <160 mmHg
Systolic BP, mmHg
Intensive
Standard
HR (95% CI)
Pint
no. of patients (%) % per year
no. of patients (%) % per year
Primary outcome
<160
≥160
211/4181 (5.0)
32/497 (6.4)
1.60
2.13
282/4204 (6.7)
37/479 (7.7)
2.16
2.49
0.579
0.74 ( )
0.86 ( )
0.2
1.0
5.0
Intensive Better
Standard Better
All-cause death
<160
≥160
126/4181 (3.0)
29/497 (5.8)
0.93
1.86
185/4204 (4.4)
25/479 (5.2)
1.37
1.62
0.072
0.68 ( )
1.16 ( )
Primary outcome and all-cause death
<160
≥160
282/4181 (6.7)
50/497 (10.1)
2.14
3.32
377/4204 (9.0)
46/479 (9.6)
2.88
3.09
0.088
0.74 ( )
1.08 ( )
Non-cardiovascular death
<160
≥160
95/4181 (2.3)
23/497 (4.6)
0.70
1.48
131/4204 (3.1)
14/479 (2.9)
0.97
0.91
0.025
0.72 ( )
1.64 ( )

7. of ≥160 mmHg (n=976)? sub-subgroup analyses
Results: Step 3, heterogeneity among patients with a baseline systolic BP
of ≥160 mmHg (n=976)? sub-subgroup analyses
Primary outcome
All-cause death
Prior CVD No
Yes
Framingham 10-yr risk score, %
≤31.3
>31.3
Age, year
<75
≥75
Antihypertensive agents
Prior CKD
0.343
0.94 ( )
0.62 ( )
0.888
0.88 ( )
0.84 ( )
HR (95% CI)
Pint
0.901
0.83 ( )
0.88 ( )
0.674
0.56 ( )
0.87 ( )
0.293
1.07 ( )
0.64 ( )
Prior CVD No
Yes
Framingham 10-yr risk score, %
≤31.3
>31.3
Age, year
<75
≥75
Antihypertensive agents
Prior CKD
0.093
1.56 ( )
0.66 ( )
0.044
2.99 ( )
0.81 ( )
HR (95% CI)
Pint
0.574
1.34 ( )
1.00 ( )
0.582
1.59 ( )
1.10 ( )
0.187
0.84 ( )
1.75 ( )
0.1
1.0
10.0
Intensive Better
Standard Better
0.1
1.0
10.0
Intensive Better
Standard Better

8. Results: Step 4, comparing patients with a baseline systolic BP of ≥160 mmHg and a Framingham 10-yr risk score of ≤31.3% to the rest of SPRINT participants
SBP-Framinghan 10-yr risk score combination
Intensive
Standard
HR (95% CI)*
Pint†
no. of patients (%) % per year
no. of patients (%) % per year
Primary outcome
0.1
1.0
10.0
Intensive Better
Standard Better
SBP ≥160/risk ≤31.3%
All others
8/244 (3.3)
235/4434 (5.3)
1.06
1.68
9/236 (3.8)
310/4447 (7.0)
1.19
2.24
0.95 ( )
0.75 ( )
0.648
All-cause death
SBP ≥160/risk ≤31.3%
All others
12/244 (4.9)
143/4434 (3.2)
1.55
1.00
4/236 (1.7)
206/4447 (4.6)
0.52
1.44
3.12 ( )
0.69 ( )
0.009
Primary outcome and all-cause death
SBP ≥160/risk ≤31.3%
All others
16/244 (6.6)
316/4434 (7.1)
2.11
2.26
11/236 (4.7)
412/4447 (9.3)
1.45
2.98
1.53 ( )
0.76 ( )
0.075
Non-cardiovascular death
SBP ≥160/risk ≤31.3%
All others
10/244 (4.1)
108/4434 (2.4)
1.29
0.75
4/236 (1.7)
141/4447 (3.2)
0.52
0.99
2.60 ( )
0.76 ( )
0.036
*Adjusted for age (treated as quintile) and sex in the subgroup of SBP ≥160 mmHg and 10-yr risk score of ≤31.3%
†Adjusted for age (treated as quintile) and sex and assuming common baseline hazard across clinic

9. Results: Step 4, comparing patients with a baseline systolic BP of ≥160 mmHg and a Framingham 10-yr risk score of ≤31.3% to the rest of SPRINT participants
SPRINT-subgroup: Baseline SBP ≥160 mmHg & 10-yr Framingham risk score ≤31.3%
SPRINT-original
Death from Any Cause
SBP 168 mmHg at baseline
SBP 125 mmHg at Year 1
SBP 140 mmHg at Year 1
† Adjusted for age (treated as quintile) and sex, and assuming common baseline hazard across clinic site due to small sample size

10. Limitations
Results from this post-hoc analysis are hypothesis-generating in nature
The subset of hypertensive patients who had had increased mortality with intensive BP control is composed of only 5% (480/9361) of SPRINT participants
-- Patients with stage 2 hypertension and a 10-year Framingham risk score of ≤30% (close to 31.3%) represent one-seventh hypertensive adults aged ≥50 years according to the National Health and Nutrition Examination Survey, 2007 to 2012
Bress AP, et al. J Am Coll Cardiol 2016;67:

11. Conclusions
Among the SPRINT participants with a baseline systolic BP of ≥160 mmHg and a lower 10- ­year Framingham risk score (≤31.3%, median), targeting a systolic BP of <120 mmHg compared with <140 mmHg resulted in an approximate 3-fold risk of death from any cause
Despite of the hypothesis-generating nature, it seems prudent to recommend targeting an SBP of <140 mmHg rather than <120 mmHg in patients with stage 2 hypertension and a 10-year Framingham risk score of ≤30% (close to 31.3%)
There was an intricate interaction between each individual’s baseline blood pressure, their inherent cardiovascular risk, and their degree of blood pressure reduction. We have to consider all three of these elements in managing hypertensive patients