1. SPRINT FROM @NEJM
BP TARGET < 120 VS < 140 MM HG
Daniel Schwartz, MD Nov 13, 2015

2. BP TARGETS
THEY KEEP CHANGING

3. WHAT’S YOUR
TARGET?

4. BACKGROUND
WHY TREAT HYPERTENSION
▸ Treatment to reduce elevated blood pressure can lead to reduction
in
▸ coronary artery disease (CAD)
▸ congestive heart failure
▸ stroke
▸ chronic kidney disease
irrespective of age, sex, race or ethnic background and HTN severity

5. BACKGROUND
OBSERVATIONAL
▸ Observational studies
▸ linear relationship between blood pressure and
cardiovascular risk down to 115/75 mm Hg
▸ J-curve - is it confounded?

6. BACKGROUND
CURRENT CHEP GUIDELINES: BP TARGETS
▸ <130/80 mm Hg: Diabetes
▸ <150 mm Hg systolic: >80 years
▸ <140/90: All else

7. BACKGROUND
IN DIABETES
▸ Action to Control Cardiovascular Risk in Diabetes
(ACCORD) trial
▸ Systolic BP < 120 mm Hg vs <140 mm Hg
▸ no difference in cardiovascular events in DM2

8. TRIAL

9. METHODOLOGY

10. TRIAL
TRIAL DESIGN
▸ randomized, controlled, open-label trial
▸ multicenter
▸ randomization stratified by site
▸ blinded outcome adjudicators (patients/researchers not blinded)
▸ primary analysis compared time to 1st occurrence of primary
outcome event with intention-to-treat
▸ independent data and safety monitoring board monitored
unblinded trial results and safety events

11. TRIAL
FUNDING
▸ NIH
▸ no industry funds

12. TRIAL
INCLUSION
▸ age >= 50 years
▸ Systolic blood pressure
▸ 130 – 180 mm Hg on 0 or 1 medication
▸ 130 – 170 mm Hg on up to 2 medications
▸ 130 – 160 mm Hg on up to 3 medications
▸ 130 – 150 mm Hg on up to 4 medications
▸ increased risk of cardiovascular events
▸ clinical or subclinical cardiovascular disease other than stroke
▸ CKD excluding polycystic kidney disease (eGFR 20-60)
▸ 10-year risk of cardiovascular disease >= 15% (Framingham)
▸ age >= 75 years

13. TRIAL
EXCLUSION
▸ Diabetes
▸ Hx of stroke
▸ An indication for a specific BP lowering medication
▸ Secondary hypertension
▸ Orthostatic BP < 110
▸ PKD, GN needing immunosuppression
▸ >1gm/day proteinuria
▸ EF < 35%
▸ Recent heart failure < 6 months, cardiac event < 3 months

14. TRIAL
INTERVENTION
▸ BP target <140 vs 120
▸ Treatment algorithm
▸ lifestyle
▸ drugs

15. TRIAL
PRIMARY OUTCOME
▸ Composite
▸ myocardial infarction
▸ acute coronary syndrome
▸ stroke
▸ acute decompensated heart failure
▸ death from cardiovascular causes

16. RESULTS

17. RESULTS
STOPPED EARLY
▸ 9361 patients enrolled
▸ Aug 20, 2015 - terminated early due to improved outcome
with intensive target

20. RESULTS
BLOOD PRESSURES
▸ Baseline
▸ 139.7/78.2 mm Hg (intensive)
▸ 139.7/78.0 mm Hg (standard)
▸ 1 year
▸ 121.4/68.7 mm Hg (intensive) with 2.8 meds
▸ 136.2/76.3 mm Hg (standard) with 1.8 meds

21. RESULTS
RESULTS
▸ Intensive-treatment
▸ 25% RRR of major
cardiovascular events (95% CI,
11 to 36)
▸ 27% RRR of death (95% CI, 10
to 40)

23. RESULTS
NNT
TO PREVENT
A PRIMARY OUTCOME EVENT: 61
DEATH FROM ANY CAUSE: 90
DEATH FROM CARDIOVASCULAR
CAUSES: 172
OVER MEDIAN 3.26 YEARS

24. RESULTS
SERIOUS ADVERSE EVENTS
▸ Intensive arm: 4.7%
vs
▸ Standard arm: 2.5% serious adverse events
(HR, 1.88; P<0.001)

26. METHODS
METHODOLOGIC ISSUES?
▸ Stopping early
▸ can overestimate benefit in small trials
▸ unlikely with > 500 primary outcome events
▸ Lack of blinding (BP can be measured)
▸ mitigated by structured assessment of outcomes and
adverse events

27. METHODS
GENERALIZABILITY
▸ Cannot apply to those with
▸ Diabetes
▸ History of Stroke
▸ Institutionalized Elderly
▸ Advanced/highly proteinuric CKD

28. METHODS
RISK VS BENEFIT
▸ Do benefits outweigh risks?

29. CURRENT GUIDELINES …
REQUIRE REVISION.
Vlado Perkovic, for the NEJM

30. TAKE AWAY
REAL WORLD
▸ BP goal of 140/90 mm Hg
▸ US: 33-50% not at target
▸ Many developing countries: >90% not at target

31. 16.8 MILLION US ADULTS
MEET INCLUSION CRITERIA
J Am Coll Cardiol. 2015;():. doi:10.1016/j.jacc.2015.10.037

32. TAKE AWAY
NEPHROLOGY PRACTICE
▸ 28% had GFR 20-60 ml/min
▸ Excluded
▸ GFR < 20
▸ Proteinuria > 1gm
▸ Excluded highest risk for progression to ESRD

33. TAKE AWAY
SIGNIFICANT EFFORT
▸ in SPRINT
▸ initial combination therapy
▸ monthly visits until BP at target

36. CLINICAL TRIALS
ARE DIFFERENT
FROM REAL LIFE

37. TAKE AWAY
REAL WORLD
▸ Adoption of lower BP targets would mean
▸ more cautious titration of medications
▸ more combination treatment
▸ more care watching for adverse effects
▸ more frequent visits
▸ addressing lifestyle issues (physical activity, salt intake, obesity,
sleep apnea, and alcohol use)
▸ population-level initiatives (eg sodium in food)

38. TAKE AWAY
MORE HELP
▸ People
▸ Nurse practitioners
▸ Physician assistants,
▸ Pharmacists
▸ Others?
▸ Treatment algorithms
▸ Algorithmic monitoring/EHRs?

39. TWITTER:
POLL
REFERENCES
@nephrologynow

40. WHAT’S YOUR
TARGET?