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==Conclusions== | ==Conclusions== | ||
In conclusion, lower systolic blood pressure targets of less than 120 mm Hg, as compared with < 140 mm Hg, in patients at high risk for cardiovascular events but without diabetes resulted in lower rates of major cardiovascular events and death from any cause.<ref name="pmid26551272">{{cite journal |vauthors=Wright JT, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV, Reboussin DM, Rahman M, Oparil S, Lewis CE, Kimmel PL, Johnson KC, Goff DC, Fine LJ, Cutler JA, Cushman WC, Cheung AK, Ambrosius WT |title=A Randomized Trial of Intensive versus Standard Blood-Pressure Control |journal=N. Engl. J. Med. |volume=373 |issue=22 |pages=2103–16 |year=2015 |pmid=26551272 |doi=10.1056/NEJMoa1511939 |url=}}</ref> | *In conclusion, lower systolic blood pressure targets of less than 120 mm Hg, as compared with < 140 mm Hg, in patients at high risk for cardiovascular events but without diabetes resulted in lower rates of major cardiovascular events and death from any cause.<ref name="pmid26551272">{{cite journal |vauthors=Wright JT, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV, Reboussin DM, Rahman M, Oparil S, Lewis CE, Kimmel PL, Johnson KC, Goff DC, Fine LJ, Cutler JA, Cushman WC, Cheung AK, Ambrosius WT |title=A Randomized Trial of Intensive versus Standard Blood-Pressure Control |journal=N. Engl. J. Med. |volume=373 |issue=22 |pages=2103–16 |year=2015 |pmid=26551272 |doi=10.1056/NEJMoa1511939 |url=}}</ref> | ||
* Positive for primary endpoint | |||
==Discussion and Limitations of the Trial== | ==Discussion and Limitations of the Trial== | ||
Revision as of 20:01, 18 January 2016
Complete Title of Study
A randomized trial of intensive versus standard blood-pressure control
Study Acronym
SPRINT
Principal Investigator, Co-investigators, and Collaborating Institutions
Principal Investigator: The SPRINT Research Group
Overview
In patients at high risk for CVD but who do not have a history of stroke or diabetes, intensive BP control (target SBP <120 mm Hg) improved CV outcomes and overall survival compared to standard therapy (target SBP 135-139 mm Hg), while modestly increasing the risk of some serious adverse events.
Disease State(s) Studied
- Cardiovascular diseases
- Hypertension
- Acute coronary disease
- Heart failure
- Stroke
- Chronic kidney disease
Study Design
- Setting: Multicenter (102 sites in the US and Puerto Rico)
- Design: Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study.
- N=9,361 patients without diabetes or stroke at elevated CV risk
Study Duration and Time-points
- Participant enrollment: 2010-2013
- Study Start Date: October 2010
- Median follow-up: 3.26 years (stopped prematurely; goal 5 years)
- Study visits: Participants were seen monthly for the first 3 months and every 3 months
Interventions
- Experimental: Intensive, target SBP <120 mm Hg (n=4,678)
- Active Comparator: Standard, target SBP 135-139 mm Hg (n=4,683)
Study Measures
- Blood pressure measurement(mmHg)
- Office visit while the patient was seated and after 5 minutes of quiet rest
- The measurements were made with the use of an automated measurement system (Model 907, Omron Healthcare)
Primary Endpoint
- First occurrence of MI, ACS, stroke, HF, or CV mortality
Secondary Endpoints
- MI
- ACS without MI
- Stroke
- HF
- CV mortality
- All-cause mortality
- Composite of primary outcome or all-cause mortality
- Of those with CKD at baseline
- ≥50% reduction in GFR, long-term HD, or renal transplant
- ≥50% reduction in GFR
- Long-term HD
- New albuminuria
- Of those without CKD at baseline
- ≥30% reduction in GFR to <60 mL/min/1.73 m2
- New albuminuria
Inclusion Criteria
- Age ≥50 years
- SBP (mmHg) in a range:
- 130-180 on ≤1 medication
- 130-170 on ≤2 medications
- 130-160 on ≤3 medications
- 130-150 on ≤4 medications
- ≥1 of the following CVD risk criteria:
- Clinical CVD (non-stroke):
- Prior MI, PCI, CABG, CEA, or carotid stenting
- Revascularized PAD
- ACS ± EKG changes, EKG changes on a stress test, or ischemic findings on other cardiac imaging
- ≥50% stenosis of coronary, carotid, or LE artery, or
- AAA ≥5 cm
- Subclinical CVD:
- Carotid artery calcium score ≥400 in prior 2 years
- ABI ≤0.90 in prior 2 years, or
- LVH on EKG, echocardiogram, or other imaging in prior 2 years
- CKD: eGFR 20-59 mL/min/1.73 m2 on MDRD in prior 6 months
- Framingham estimated 10-year CVD risk ≥15% in prior 12 months
- Age ≥75 years
- Clinical CVD (non-stroke):
Exclusion Criteria
- DM
- Stroke
- Not on disease-appropriate antihypertensives (eg, beta blocker and recent MI)
- Secondary cause of hypertension
- If able to stand, 1 min standing SBP <110
- Proteinuria in any of the following ranges:
- ≥1g/day urine protein
- ≥600 mg/day urine albumin
- Spot protein:creatinine ≥1g protein/g creatinine
- Spot albumin:creatinine ≥600 mg/g creatinine
- Urine dipstick ≥2+ protein if none of the above are available
- Polycystic kidney disease
- Glomerulonephritis
- eGFR < 20 mL/min/1.73 m2
- CV event, procedure, or UA hospitalization in prior 3 months
- Symptomatic HF in prior 6 mo
- LVEF <35%
- Life-limiting illness
- Poor adherence
- Organ transplant
- Unintentional weight loss >10% in prior 6 months
- Pregnancy
Outcome: Primary Endpoint
- First ACS, stroke, HF, or CV death
- 5.2% vs. 6.8% (HR 0.75; 95% CI 0.64-0.89; P<0.001; NNT 63)
Outcome: Secondary Endpoint
- MI
- 2.1% vs. 2.5% (HR 0.83; 95% CI 0.64-1.09; P=0.19)
- ACS without MI
- 0.9% vs. 0.9% (HR 1.00; 95% CI 0.64-1.55; P=0.99)
- Stroke
- 1.3% vs. 1.5% (HR 0.89; 95% CI 0.62-1.25; P=0.50)
- HF
- 1.3% vs. 2.1% (HR 0.62; 95% CI 0.45-0.84; P=0.002; NNT 125)
- CV mortality
- 0.8% vs. 1.4% (HR 0.57; 95% CI 0.38-0.85; P=0.005; NNT 167)
- All-cause mortality
- 3.3% vs. 4.5% (HR 0.73; 95% CI 0.60-0.90; P=0.003; NNT 83)
- Composite of primary outcome or all-cause mortality
- 7.1% vs. 9.0% (HR 0.78; 95% CI 0.67-0.90; P<0.001; NNT 53)
- Of those with CKD at baseline
- ≥50% reduction in GFR, long-term HD, or renal transplant: 1.1% vs. 1.1% (HR 0.89; 95% CI 0.42-1.87; P=0.76)
- ≥50% reduction in GFR: 0.8% vs. 0.8% (HR 0.87; 95% CI 0.36-2.07; P=0.75)
- Long-term HD: 0.5% vs. 0.8% (HR 0.57; 95% CI 0.19-2.54; P=0.27)
- Renal transplant: none
- New albuminuria: 9.3% vs. 11.8% (HR 0.72; 95% CI 0.48-1.07; P=0.11)
- Above defined as doubling of albumin:creatinine ratio from <10 to >10 mg albumin/g creatinine.
- Of those without CKD at baseline
- ≥30% reduction in GFR to <60 mL/min/1.73 m2: 3.8% vs. 1.1% (HR 3.49; 95% CI 2.44-5.10; P<0.001; NNH 37)
- New albuminuria: 6.2% vs. 7.4% (HR 0.81; 95% CI 0.63-1.04; P=0.10)
Outcome: Exploratory Endpoints
- BP at year 1
- SBP: 121.4 vs. 136.2 mmHg
- DBP: 68.7 vs. 76.3 mmHg
- Number of antihypertensives
- 2.8 vs. 1.8
- None: 2.7% vs. 11.3%
- 1: 10.5% vs. 31.1%
- 2: 30.5% vs. 33.3%
- 3: 31.8% vs. 17.2%
- ≥4: 24.3% vs. 6.9%
- Breakdown of medication utilization is presented on page 30 of the supplementary appendix.[1]
Subgroup Analysis
There was no significant interaction for the primary outcome by CKD at baseline, age, sex, race, prior CVD, or SBP.
Outcome: Safety endpoints
- Serious adverse event (SAE)
- 38.3% vs. 37.1% (HR 1.04; P=0.25)
- Hypotension: 2.4% vs. 1.4% (HR 1.67; P=0.001; NNH 100)
- Syncope: 2.3% vs. 1.7% (HR 1.33; P=0.05; NNH 167)
- Bradycardia: 1.9% vs. 1.6% (HR 1.19; P=0.28)
- Electrolyte abnormality: 3.1% vs. 2.3% (HR 1.35; P=0.02; NNH 125)
- Fall with injury: 2.2% vs. 2.3% (HR 0.95; P=0.71)
- AKI/ARF: 4.1% vs. 2.5% (HR 1.66; P<0.001; NNH 63)
- SAE possibly or definitely associated with the intervention 4.7% vs. 2.5% (HR 1.88; P<0.001; NNH 45)
- Above is from page 33 of supplemental appendix.[1]
- SAE possibly or definitely associated with the intervention 4.7% vs. 2.5% (HR 1.88; P<0.001; NNH 45)
- SAE or ED visit
- Hypotension: 3.4% vs. 2.0% (HR 1.70; P<0.001; NNH 71)
- Syncope: 3.5% vs. 2.4% (HR 1.44; P=0.003; NNH 91)
- Bradycardia: 2.2% vs. 1.8% (HR 1.25; P=0.13)
- Electrolyte abnormality: 3.8% vs. 2.8% (HR 1.38; P=0.006; NNH 100)
- Fall with injury: 7.1% vs. 7.1% (HR 1.00; P=0.97)
- AKI/ARF: 4.4% vs. 2.6% (HR 1.71; P<0.001; NNH 56)
- Laboratory abnormality
- Na <130 mmol/L: 3.8% vs. 2.1% (HR 1.76; P<0.001; NNH 59)
- Na >150 mmol/L: 0.1% vs. 0% (HR not given; P=0.02; NNH 1,000)
- K <3 mmol/L: 2.4% vs. 1.6% (HR 1.50; P=0.006; NNH 125)
- K >5.5 mmol/L: 3.8% vs. 3.7% (HR 1.00; P=0.97)
- Orthostatic hypotension
- 16.6% vs. 18.3% (HR 0.88; P=0.01; NNT 59)
- With dizziness: 1.3% vs. 1.5% (HR 0.85; P=0.35)
Statistical Analysis
- 88.7% power to detect a 20% effect with respect to the primary outcome
- Cox proportional-hazards regression with two-sided tests (HR)
- 5% level of significance
- Analysis: Intention-to-treat
Conclusions
- In conclusion, lower systolic blood pressure targets of less than 120 mm Hg, as compared with < 140 mm Hg, in patients at high risk for cardiovascular events but without diabetes resulted in lower rates of major cardiovascular events and death from any cause.[1]
- Positive for primary endpoint
Discussion and Limitations of the Trial
- Lack of generalizability to patients with diabetes, those with prior stroke, and those younger than 50 years of age.[2]
- Recruitment limitations, lack of enrollment to older adults residing in nursing homes or assisted-living facilities.
- Safety surveillance and effects of lower blood pressure on the central nervous system and kidney cannot be reasonably interpreted until the analysis of these endpoints is completed.
Commentary
Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [1]
- Assess kidney injury related to lower systolic blood pressure. Long term adverse renal outcome.
- Meta-analysis on existing trials evaluating identical systolic-blood pressure targets.
- Can we know more characteristics on patients lost in follow-up?
- Intracranial hypoperfusion has been linked to cognitive decline in the elderly, which may be worsened by lower BP targets, although SPRINT was likely too short to detect a meaningful change in cognitive status.
Slides
Video Commentary
External sites for further information
References
- ↑ 1.0 1.1 1.2 Wright JT, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV, Reboussin DM, Rahman M, Oparil S, Lewis CE, Kimmel PL, Johnson KC, Goff DC, Fine LJ, Cutler JA, Cushman WC, Cheung AK, Ambrosius WT (2015). "A Randomized Trial of Intensive versus Standard Blood-Pressure Control". N. Engl. J. Med. 373 (22): 2103–16. doi:10.1056/NEJMoa1511939. PMID 26551272.
- ↑ Perkovic V and Rodgers A. "Editorial: Redefining blood-pressure targets -- SPRINT starts the marathon." The New England Journal of Medicine. epub 2015-11-09.