Is 120 the new 140? 

A Randomized Trial of Intensive versus Standard Blood-Pressure Control.

SPRINT Research GroupWright JT JrWilliamson JDWhelton PKSnyder JKSink KMRocco MVReboussin DMRahman MOparil SLewis CEKimmel PLJohnson KCGoff DC JrFine LJCutler JACushman WCCheung AKAmbrosius WT.

Collaborators (844)

November 9, 2015 DOI: 10.1056/NEJMoa1511939

PMID: 26551272

Link to full paper at NEJM

#NephJC tweetchat

Tuesday Nov 10 9 pm EDT

Wednesday Nov 11 8 pm GMT and 12 noon PST

The Landmark SPRINT trial results were finally revealed in all their glory on Nov 9th at 2 pm EDT at the AHA meeting in Orlando. Before we discuss the results, here are some of the previous publications from the SPRINT research group:

Storify of the pre-publication speculation:

Storify of the #NephJC chat

 

Pre Chat Summary of SPRINT Methods and Results

The SPRINT trial, funded by the NHLBI arm of the NIH (and co-sponsored by the NIDDK, NIMDS and NIA), was based on a working group report (PDF link) from 2007, which identified the question of targeting low blood pressure (i.e. 120 mm Hg) in non-diabetics (since ACCORD was ongoing in Diabetics then) as a priority.

Methods

Overall, it took a whopping 102 centers (grouped under 5 clinical center networks) to enroll the patients into this trial. 

Inclusion Criteria:

  • At least 50 years old
  • Systolic blood pressure
  1. SBP: 130 – 180 mm Hg on 0 or 1 medication 
  2. SBP: 130 – 170 mm Hg on up to 2 medications 
  3. SBP: 130 – 160 mm Hg on up to 3 medications 
  4. SBP: 130 – 150 mm Hg on up to 4 medications
  • There are no diastolic blood pressure (DBP) inclusion criteria
  • Risk (one or more of the following):

a)  Presence of clinical or subclinical cardiovascular disease other than stroke (based on detailed definitions)

b)  CKD, defined as MDRD eGFR 20 – 59 ml/min/1.73m2  within the past 6 months. 

c)  Framingham Risk Score for 10-year CVD risk ≥ 15% 

d)  Age ≥ 75 years.

Selected Exclusion Criteria

  • An indication for a specific BP lowering medication
  • Known secondary cause of hypertension that causes concern regarding safety of the protocol.
  • One minute standing SBP < 110 mm Hg. Not applicable if unable to stand due to wheelchair use
  • Proteinuria (> 1g/day or albuminuria >600 mg/day or equivalent PCR/ACR or 2+ on dipstick)
  • Arm circumference too large or small to allow accurate blood pressure measurement with available devices
  • Diabetes
  • History of stroke (not CE or stunting)
  • Diagnosis of polycystic kidney disease
  • Glomerulonephritis treated with or likely to be treated with immunosuppressive therapy
  • eGFR < 20 ml/min /1.73m2 or end-stage renal disease (ESRD)
  • Cardiovascular event or procedure (as defined above as clinical CVD for study entry)
  • A medical condition likely to limit survival to less than 3 years, 
  • Any factors judged by the clinic team to be likely to limit adherence to interventions.
  • Residence in a nursing home. Persons residing in an assisted living or retirement community are eligible if they meet the other criteria.
  • Any organ transplant

Intervention

This was a randomized, controlled, open label trial.  Eligible participants were assigned to a systolic blood-pressure target of either less than 140 mm Hg (the standard-treatment group) or less than 120 mm Hg (the intensive-treatment group). The study investigators were not blinded - but the outcome adjudicators were blinded. BP was measured quite meticulously with automated oscillometric BP devices (which discard the first reading, and take 3-5 consecutive readings and give an average) which approximate true resting blood pressure reasonably. Patients were seen quite frequently (and decreasing/stopping medications if BP was too low, especially in the standard arm was a notable feature). The algorithms and formulary can be seen from the supplementary figures from the appendix: 

Figure S1

Figure S1

Figure S2

Figure S2

Table S1

Table S1

Results

As planned, 9361 participants were enrolled. Details can be seen in figure 1 and table 1. Of note, ~2600 patients had CKD (eGFR 20-59) making it one of the largest hypertension trials in this population. 

Figure 1

Figure 1

Table 1

Table 1

There was a nice separation of the systolic and diastolic blood pressures (seen in figure 2 and Supp figure S4). 

Outcomes

With respect to the primary outcome (a kind of MACE outcome, including heart failure), there was a nice separation at one year, with an overall HR of 0.75 (favouring intensive treatment) and an NNT of ~ 60 over 3.7 years. For all-cause mortality, this difference is noticeable at about 2 years, with a HR of 0.73 (and an NNT ~ 90 over the 3.7 years). 

The details of the primary outcome are available in table 2 (notable being the decrease in eGFR seen in the intensive arm in the subgroup with GFR > 60)

Table 2 from SPRINT

Table 2 from SPRINT

Notably, the intensive blood pressure arm resulted in no increase in overall adverse events (though note the increase in AKI)

Table 3

Table 3

There were a lot of pre-specified subgroups, and none of them displayed any heterogeneity (see figure 4 for primary outcome, and figure S5 for mortality - shown below)

Discussion

Apart from the discussion in the article itself, there were many simultaneous publications:

In NEJM

In the Hypertension

  • 3 editorials (PDF available at this link)

New York Times

Medscape

On the ACC website

Multiple quick-read posts, by George Bakris (who says, "The findings related to all-cause mortality are a mystery to me and have no plausible explanation"!),  Susan Steigerwalt and Roger Brook and Tim Eagle

An analysis by Adam Bress et al using NHANES in JACC, suggesting 20% US adults with hypertension (~ 16 million overall) would fit SPRINT criteria

JASN

A commentary by Glenn Chertow et al (who were actually involved in SPRINT)

Wikidoc C.Michael Gibson

Interview with Author: Methods  and Results

A critical take from Alan Cassels

#NephJC tweetchat

Tuesday Nov 10 9 pm EDT

Wednesday Nov 11 8 pm GMT and 12 noon PST

Summary prepared by Swapnil Hiremath