1. Professor & Chair of Department of Family Medicine
Controversies in the Diagnosis &Treatment of Hypertension: Interpreting JNC 8 after SPRINT
UW Family Medicine
End of Quarter
Paul James MD
Professor & Chair of Department of Family Medicine
School of Medicine
University of Iowa

2. Disclosure: Relationships with Industry Conflicts of Interests
I have no financial interests to report

3. Learning Objectives: Participants will be able to:
Learners will be able to :
Better Assess Goals for Hypertension treatment based on JNC 8, SPRINT and HOPE 3
Understand Absolute Risk Reduction (ARR) and its relation to clinical decision making
Understand Relative Risk Reduction (RRR) and how this may inflate the treatment effect
Learners will be able to use Hypertension as an example of how our increasing focus on disease prevention expands diagnoses and treatment making more people sick and fewer healthy

4. 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report from the Panel Members Appointed to the Eighth Joint National Committee (JNC 8)
James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, Lackland DT, Lefevre ML, Mackenzie TD, Ogedegbe O, Smith SC Jr, Svetkey LP, Taler SJ, Townsend RR, Wright JT Jr, Narva AS, Ortiz E
James PA, Oparil S, Carter BL et al. JAMA. 2014; 311 (February 5):
*4 members had relationships to disclose; 13 had no relationships to disclose. Panel members disclosed their relationships and recused themselves from voting on evidence statements and recommendations relevant to their relationships.

5. NHLBI Systematic Review and Guideline Development Process
Literature Searched;
Eligible Studies
Identified
Studies Quality Rated;
Data Abstracted
Evidence Tables
Developed;
Body of Evidence
Summarized
Graded Evidence
Statements &
Recommendations
Developed
Expert Panel
Selected
Topic Area
Identified
Critical Questions
& Study Eligibility
Criteria Identified
External Review
of Guideline
Drafts; Revised
as Needed
Guidelines
Disseminated &
Implemented
Here we see the series of steps for the systematic reviews and guidelines development – from identification of the topic area to dissemination of the final guidelines.
The blue boxes indicate the same steps that would be conducted for a primary research study: identifying a research question, determining subject eligibility, collecting data, creating a database, analyzing and interpreting the data.

6. 2014 Goal Blood Pressures for Adults: Quick Summary
For age 60 years and older without diabetes or kidney disease, strong evidence supports Goal BP < 150/90 based on Grade A level evidence
For all others, we recommend Goal BP < 140/90 based on expert opinion

7. Initial Drug Treatment Recommendations for High Blood Pressure
Non-Black Population without DM or CKD: Thiazide-type diuretic, CCB, ACEI or ARB
B Level Evidence
Black Population including those with DM: Thiazide-type diuretic or CCB
B Level Evidence for general Population and C Level Evidence for DM

8. Initial Drug Treatment Recommendations for High Blood Pressure
CKD Population (Black and non-Black, DM or not DM): ACEI or ARB (but not both together in any circumstance)
B Level Evidence

9. SPRINT Large RCT of 9361 subjects
Does treating BP to lower goal (BP <120 mmHg) compared to goal BP < 140 mmHg result in improved outcomes?
This was planned before the JNC 8 Panel was convened. This is a planned difference of 20 mmHg in BP. That is a big difference. We know that small differences are less likely to show benefit. This is a well planned study.
A Randomized Trial of Intensive versus Standard Blood-Pressure Control. SPRINT Research Group, Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV, Reboussin DM, Rahman M, Oparil S, Lewis CE, Kimmel PL, Johnson KC, Goff DC Jr, Fine LJ, Cutler JA, Cushman WC, Cheung AK, Ambrosius WT.
N Engl J Med Nov 26;373(22): doi: /NEJMoa Epub Nov 9. PMID:

10. SPRINT
P: 50 years or older with Systolic BP mm Hg & increased CVD Risk but not stroke or diabetes (9361)
I: More intensive Medication Vs “Standard” BP Control
C: Goal BP < 120 vs BP < 140 mm Hg
O: Composite Outcome of MI, ACS, stroke, HF, or CV death
Myocardial Infarction, Acute Coronary Syndrome, Stroke , Heart Failure or Cardiovascular Death
Average BP at entry: 140/78
Actual BP lowering was Systolic 14.8 mmHg and Diastolic was 7.6 mmHg at year 1.
Average over 3 years was mm Hg compared with mm Hg. Change = mmHg

11. Primary and Secondary Outcomes and Renal Outcomes.
The SPRINT Research Group. N Engl J Med 2015;373:

12. Results:
Relative Risk Reduction focuses on the number of events prevented (CV Death, MI, ACS, CHF or Stroke). It is a measure that maximizes the clinical significance of a trial.
SPRINT showed a 25% reduction in composite measures. Reduction from 6.8% to 5.2%.
RRR = /0.068 = 0.24

13. Results:
Absolute Risk Reduction (ARR) provides more information clinically about the population. It is for all who took the medications.
From the ARR, we can calculate the work of treating enough patients for 1 person to benefit or the Number Needed to Treat (NNT)
NNT = 1/ARR
ARR = – = Or 1.6% likelihood of benefitting from more aggressive treatment.
More useful to clinicians because it shows the effort required to achieve the RRR.

14. SPRINT Results Number Needed to Treat (NNT) = 63 based on ARR of 1.6%
A small minority of patients treated (1.6%) will benefit from the new goal BP < 120 mmHg
However, we will have to treat over 60 people to benefit one person.

15. SPRINT Results: stated differently
Of 1000 people treated aggressively to a goal of 120 mmHg for over 3 years,16 people will benefit, 22 will be harmed with serious adverse events, and over 980 will not see any benefit.
It would be useful to have a bio-marker to identify the 16 patients who might be more likely to benefit
Let your patients decide? What would you decide?
A moment about Harms

16. Harms
SPRINT investigators compare the harms in this study (more frequent than the improved outcome) to the severity of the CV death, MI, ACS, HF and stroke
Harms may be worthwhile if we are confident that we will see the benefit, less so if we don’t.
Describe SAE’s: An event that was fatal or life threatening, resulting in significant or persistent disability, requiring or prolonging a hospitalization, or was an important medical event that the investigator judged to be a significant hazard or harm to the participant that may have required medical or surgical intervention to prevent one of the other events listed. Above”
Real comparison should be to those who feel healthy and are not likely to benefit

17. Relationship between the Spectrum of the Abnormality and Treatment Benefit in Hypertension
From Over-Diagnosed: Making People Sick in the Pursuit of Health, Welch, HG, Schwartz, LM & Woloshin S., Beacon Press, Boston MA Please insert if possible as a footnote.
Over-Diagnosed. Making People Sick in the Pursuit of Health. Welch HG, Schwartz LM, Woloshin S. Beacon Press. 1/3/2012. ISBN:

18. Benefit across the Spectrum of Hypertension*
Degree of Hypertension
5-year Risk of Bad Event
No Treatment Treatment
Chance of Benefit
Number needed to Treat
Severe
[Diastolic BP ]
80% 8%
72%
1.4
Moderate10
[Diastolic BP ]
38%
12%
26% 4
Mild
[Diastolic BP ]
32%
23% 9% 11
Very Mild11
[Diastolic BP ] 3% 6%
1812
Mild to Severe** [Systolic BP ]
6.8%*
5.2%*
1.6%*
63*
From Over-Diagnosed: Making People Sick in the Pursuit of Health, Welch, HG, Schwartz, LM & Woloshin S., Beacon Press, Boston MA Please insert if possible as a footnote
Severe HTN: from the VA Coop Study (1967)
Moderate: JAMA:1970 “Effect of Morbidity on Treatment in Hypertension: II. Results in Patients with Diastolic BP averaging mmHg”
Very Mild HTN: JD Neaton, RH Grimm, RJ Prineas et al., “Treatment of Mild Hypertension Study: Final Results” JAMA (270) p
*Over-Diagnosed. Making People Sick in the Pursuit of Health. Welch HG, Schwartz LM, Woloshin S. Beacon Press. 1/3/2012. ISBN:
**From SPRINT. No Treatment Group is Usual Treatment and Treatment Group is Intensive BP Goal< 120 mmHg and at 3.2 years instead of 5.

19. HOPE 3 Trial
Tested concept of Poly-pill in population at moderate risk for CV Disease
Candesartan (ARB) and HCTZ versus Placebo
2 other interventions were compared: Rosuvastatin alone, and Rosuvastatin + Candesartan/HCTZ together

20. HOPE 3 Trial Randomized Controlled Clinical Trial
Intermediate C-V Risk patients
Over 12,000 subjects
Average BP reduction was Systolic 6.2 mmHg and Diastolic 3.2 mmHg

21. HOPE 3 Trial Results
No benefit from lowering Blood Pressure at over 5 years

22. Summary
Evidence demonstrates that for elderly without diabetes and at high CV Risk, a goal BP < 120 mmHg significantly reduces Stroke, MI, ACS, HF and CV death in a small number of patients.
This effect has not been shown in those at intermediate risk or who are younger

23. Summary
Patients and their primary care physicians must decide whether the identified benefit is worth the costs
Patient preferences, values, worries and personal factors should guide your therapeutic recommendations

24. Questions?

25. Quaternary Prevention
Doctor Patient Interaction on Prevention
Secondary Prevention
Primary Prevention
Well-being
Risk Factors
Disease
Symptoms
Tertiary Prevention
Quaternary Prevention