1. Hypertension in the Post SPRINT era
Mahboob Rahman MD, MS
Division of Nephrology and Hypertension
University Hospitals Cleveland Medical Center
Case Western Reserve University
Louis Stokes Cleveland VA Medical Center
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2. Outline Rationale for intensive blood pressure lowering
Main results of SPRINT and ACCORD
Implications for practice
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3. What “goal” blood pressure should you target in hypertensive patients?
2014
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4. Why should we consider a lower BP goal?
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5. Ischemic Heart Disease Mortality Rate
in Each Decade of Age
SBP
DBP
Age at risk:
256
256
80-89 y
128
128
70-79 y 64 64
60-69 y 32 32
IHD mortality
(absolute risk and 95% CI)
50-59 y 16 16
40-49 y 8 8 4 4 2 2 1 1
120
140
160
180 70 80 90
100
110
Usual SBP (mm Hg)
Usual DBP (mm Hg)
Lancet. 2002;360:
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6. POTENTIAL COSTS / RISKS OF LOWER BP TARGETS
Increased cost of medications
Increased risk of medication side effects
Increased clinic visits
Increased monitoring required
Potential increased risk of lower BP goals
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8. SPRINT Research Question
Examine effect of more intensive high blood pressure treatment than is currently recommended
Randomized Controlled Trial
Intensive Treatment
Goal SBP < 120 mm Hg
Standard Treatment
Goal SBP < 140 mm Hg
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9. 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
Adherence concerns
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10. Location of 102 SPRINT Clinical Centers
Clinical Center Networks
-Ohio Southeast -Utah UAB VA
Central Laboratory
MRI Reading Center
Project Office, NIH
Coordinating Center
Wake Forest School of Medicine
ECG Reading Center
Drug Distribution Center
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11. Demographic and Baseline Characteristics
Total
N=9361
Intensive
N=4678
Standard
N=4683
Mean (SD) age, years
67.9 (9.4)
67.9 (9.5)
% ≥75 years
28.2%
Female, %
35.6%
36.0%
35.2%
White, %
57.7%
African-American, %
29.9%
29.5%
30.4%
Hispanic, %
10.5%
10.8%
10.3%
Prior CVD, %
20.1%
20.0%
Taking antihypertensive meds, %
90.6%
90.8%
90.4%
Mean (SD) number of antihypertensive meds
1.8 (1.0)
Mean (SD) Baseline BP, mm Hg
Systolic
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)
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12. Systolic BP During Follow-up
Average SBP
(During Follow-up)
Standard: mm Hg
Intensive: mm Hg
Standard
Intensive
Average number of
antihypertensive
medications
Number of
participants
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13. Decision to Stop BP Intervention
On August 20th, 2015, after 3.2 years of follow up, NHLBI Director accepted DSMB recommendation to inform SPRINT investigators and participants of CVD results
Concurrently, decision made to stop BP intervention
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15. SPRINT Primary Outcome Results
Hazard Ratio = 0.75 (95% CI: 0.64 to 0.89)
Standard
(319 events)
25% Lower risk of CV events
Intensive
(243 events)
Number of
Participants
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16. All-cause Mortality Standard Intensive 27% Lower risk of mortality
Hazard Ratio = 0.73 (95% CI: 0.60 to 0.90)
27% Lower risk of
mortality
Standard
(210 deaths)
Intensive
(155 deaths)
Number of
Participants
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Intensive

17. Primary Outcome in Pre-specified Subgroups
*Treatment by subgroup interaction
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20. Serious Adverse Events* (SAE)
 All SAE reports
% of Participants
Intensive
Standard
HR (P Value)
38.3
37.1
1.04 (0.25)
  Hypotension
2.4
1.4
1.67 (0.001)
  Syncope
2.3
1.7
1.33 (0.05)
Injurious fall
2.2
0.95 (0.71)
  Bradycardia
1.9
1.6
1.19 (0.28)
  Electrolyte abnormality
3.1
1.35 (0.02)
Acute kidney injury
4.1
2.5
1.66 (<0.001)
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21. Number (%) of Participants Intensive Standard HR (P Value)
Number (%) of Participants
Intensive
Standard
HR (P Value)
   Signs and Symptoms
Orthostatic hypotension2
16.6
18.3
0.88 (0.013)
Orthostatic hypotension with dizziness
1.3
1.5
0.85 (0.35)
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24. What about BP goals in diabetic patients?
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25. ACCORD BP-Lowering: Reduction of SBP to <120 mmHg significantly Reduces the Rate of STROKE
Intensive Therapy
(n = 2363)
Standard Therapy
(n = 2371)
Outcome
Number of Events
%/Year
Hazard Ratio
(95% CI) P
Value
Primary outcome*
208
1.87
237
2.09
0.88 ( )
0.20
Prespecified secondary outcomes
Nonfatal MI
126
1.13
146
1.28
0.87 ( )
0.25
Any stroke 36
0.32 62
0.53
0.59 ( )
0.01
Nonfatal stroke 34
0.30 55
0.47
0.63 ( )
0.03
Death from any cause
150
144
1.19
1.07 ( )
0.55
Death from CV cause 60
0.52 58
0.49
1.06 ( )
0.74
Primary outcome plus revascularization or nonfatal heart disease
521
5.10
551
5.31
0.95 ( )
0.40
Major coronary disease event†
253
2.31
270
2.41
0.94 ( )
0.50
Fatal or nonfatal heart failure 83
0.73 90
0.78
0.94 ( )
0.67
*Primary outcome: composite of nonfatal MI, nonfatal stroke, or death from CV causes
†Major coronary disease events included fatal coronary events, nonfatal MI, and unstable angina
ACCORD: Action to Control Cardiovascular Risk in Diabetes Study
The ACCORD Study Group. N Engl J. Med. 2010;doi: /NEJMoa
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26. Antihypertensive meds Primary outcome
ACCORD
SPRINT
Patient Population
All diabetic
CKD excluded
All non-diabetic
Older, CKD
Interventions
3 (factorial design) 1
Sample size
 4733
9200
Event rate
 2-2.2% per year (lower than expected)
 1.6-2% (as expected)
Antihypertensive meds
More HCTZ
More chlorthalidone
Primary outcome
 CVD Death, Non-fatal MI, Nonfatal stroke
MI, ACS, Stroke
HF CVD death
Main results
HR 0.88 (0.73 to 1.06), p=0.2
HR 0.75 (0.64 to 0.89) p<0.05)
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27. Perkovic B and Rodgers A. N Engl J Med. 2015;373:2175-2178.
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28. SPRINT OUTCOMES IN PREDIABETICS VS. NORMOGLYCEMICS
Incidence rates and hazard ratios for study outcomes by treatment arm among those with normoglycemia and prediabetes at baseline
Outcome
Normoglycemia
FSG < 100 mg/dL
Prediabetes
FSG ≥ 100 mg/dL
P for
Interaction
Intensive
(n=2,721)
Standard
(n=2,704)
Hazard Ratio
(95% CI)
(n=1,941)
(n=1,957)
Primary outcome
142 (1.7)
174 (2.1)
0.83 ( )
101 (1.6)
144 (2.3)
0.69 ( )
0.30 MI
57 (0.7)
72 (0.8)
0.80 ( )
40 (0.6)
44 (0.7)
0.95 ( )
0.56
ACS
23 (0.3)
17 (0.2)
1.32 ( )
17 (0.3)
23 (0.4)
0.76 ( )
0.23
Stroke
36 (0.4)
32 (0.4)
1.19 ( )
26 (0.4)
38 (0.6)
0.72 ( )
0.16
Heart failure
37 (0.4)
52 (0.6)
0.72 ( )
25 (0.4)
48 (0.8)
0.47 ( )
0.19
CVD Death
21 (0.2)
0.62 ( )
16 (0.3)
27 (0.4)
0.56 ( )
0.81
All-cause Death
89 (1.0)
125 (1.4)
0.71 ( )
65 (1)
84 (1.3)
0.77 ( )
0.74
All SEAs
1052 (38.7)
1000 (37.0)
1.06 ( )
737 (38)
733 (37.5)
1.03 ( )
0.67
Hypotension
61 (2.2)
44 (1.6)
1.33 ( )
49 (2.5)
22 (1.1)
2.38 ( )
0.08
Syncope
66 (2.4)
46 (1.7)
1.42 ( )
40 (2.1)
34 (1.7)
1.20 ( )
0.58
Bradycardia
51 (1.9)
41 (1.5)
1.20 ( )
36 (1.9)
32 (1.6)
1.10 ( )
0.79
Electrolyte abnrm
88 (3.2)
60 (2.2)
1.45 ( )
56 (2.9)
47 (2.4)
1.17( )
0.41
Numbers are counts and annual rates. CVD=cardiovascular disease, CI= Confidence interval, FSG= Fasting serum glucose, ACE =acute coronary syndrome, abnrm=abnormality, MI=myocardial infarction
Bress A, Beddhu S, King J, et al. Intensive blood pressure control reduces cardiovascular events in patients with prediabetes. Presented at: American Diabetes Association 77th Scientific Sessions; June 9-13, 2017.
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30. American Heart Association guidelines to be released this year
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31. So what does all this mean?
Ensure standard practices for measuring BP in the office
The field is moving toward more intensive blood pressure lowering
New guidelines will likely recommend lower goals
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32. Clinicians need to discuss risks benefits with individual participants
Appreciate that tighter blood pressure control will require more medications, office visits and cost
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33. Policy makers and health care systems will have to consider costs of lowering blood pressure in balance with long term lowering of cardiovascular risk
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34. Thank you
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