Systolic Blood Pressure Intervention Trial - SPRINT
Contribution To Literature:
The SPRINT trial showed that intensive BP control to SBP <120 mm Hg results in significant cardiovascular benefit in high-risk patients with hypertension compared with routine BP control to <140 mm Hg.
The goal of the trial was to compare the safety and efficacy of intensive lowering of systolic blood pressure (SBP) to <120 mm Hg versus routine management to <140 mm Hg.
Patients were randomized to intensive SBP lowering (target <120 mm Hg) or routine SBP management (target <140 mm Hg).
- Total number of enrollees: 9,361
- Duration of follow-up: 5 years (median 3.26 years)
- Age ≥50 years
- Hypertension with SBP ≥130 mm Hg
At least one risk factor for heart disease:
- Presence of clinical or subclinical cardiovascular disease other than stroke
- Chronic kidney disease, defined as estimated glomerular filtration rate (eGFR) 20-59 ml/min/1.73 m2
- A Framingham Risk Score for 10-year cardiovascular disease risk ≥15%
- Age >75 years
- An indication for a specific BP-lowering medication that the person is not taking and the person has not been documented to be intolerant of the medication class
- Known secondary cause of hypertension
- One-minute standing SBP <110 mm Hg
- Arm circumference too large or small to allow accurate BP measurement with available devices
- Diabetes mellitus
- History of stroke
- Polycystic kidney disease
- Glomerulonephritis treated with or likely to be treated with immunosuppressive therapy
- eGFR <20 ml/min/1.73 m2 or end-stage renal disease
- Cardiovascular event or procedure or hospitalization for unstable angina within last 3 months
- Symptomatic heart failure within the past 6 months or left ventricular ejection fraction <35%
- A medical condition likely to limit survival to <3 years or a malignancy other than nonmelanoma skin cancer within the last 2 years
- Organ transplant
The trial was terminated early due to overwhelming evidence of benefit. The primary outcome, myocardial infarction (MI), acute coronary syndrome (ACS), stroke, congestive heart failure (CHF), or cardiovascular (CV) death, was significantly lowered in the intensive BP management arm compared with the routine management arm (5.2% vs. 6.8%, hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.64–0.89; p < 0.0001).
Individual components (event rates for intensive vs. routine management, absolute event rates):
- MI: 2.1% vs. 2.5%, p = 0.19
- ACS: 0.9% vs. 0.9%, p = 0.99
- Stroke: 1.3% vs. 1.5%, p = 0.5
- CHF: 1.3% vs. 2.1%, p = 0.002
- CV death: 0.8% vs. 1.4%, p = 0.0005
Important secondary endpoints for intensive vs. routine BP control, absolute event rates:
- Mortality: 3.3% vs. 4.5%, p = 0.0003
- Among patients with chronic kidney disease: composite renal endpoint (decrease in GFR ≥50%, need for HD, renal transplant); 1.1% vs. 1.1%, p = 0.76
- Among patients without CKD: ≥30% decline in GFR to <60 ml/min: 3.8% vs. 1.1%, p < 0.001
- Hypotension: 2.4% vs. 1.4%, p = 0.001
- Syncope: 2.3% vs. 1.7%, p = 0.05
- Hyponatremia: 3.8% vs. 2.1%, p < 0.001
Generalizability to the US population: Based on National Health and Nutrition Examination Survey (NHANES) data from 2007 to 2012, it appears that 7.6% or 16.8 million US adults, and 16.7% or 8.2 million of those with treated hypertension, would meet the SPRINT eligibility criteria. Thus, 8.6 million of US adults are not currently treated for hypertension based on the SPRINT trial, highlighting the public health importance of these findings.
Among patients aged ≥75 years (n = 2,636), primary outcomes for intensive vs. routine BP management were 7.7% vs. 11.2%, p < 0.05. All-cause mortality was 5.5% vs. 8.1%, respectively, p < 0.05.
Left ventricular hypertrophy (LVH) progression (n = 8,164): Among participants without baseline LVH, intensive BP lowering reduced LVH on electrocardiogram (HR 0.54, 95% CI 0.43-0.68). Similarly, among participants with baseline LVH (n = 605, 7.4%), intensive BP lowering was more likely to show LVH regression (HR 1.66, 95% CI 1.31-2.11). Adjusting for LVH did not attenuate the risk of CV disease with intensive lowering, suggesting that LVH improvement was not a significant driver of CV disease reduction with intensive BP lowering.
Effect on patient-reported outcomes: Patient-reported outcome measures included the scores on the Physical Component Summary (PCS) and Mental Component Summary (MCS) of the Veterans RAND 12-Item Health Survey, the Patient Health Questionnaire 9-item depression scale (PHQ-9), among others. Participants who received intensive treatment received an average of one additional antihypertensive medication, and the systolic blood pressure was 14.8 mm Hg (95% confidence interval, 14.3-15.4) lower in the group that received intensive treatment than in the group that received standard treatment. Mean PCS, MCS, and PHQ-9 scores were relatively stable over a median of 3 years of follow-up, with no significant differences between the two treatment groups. Satisfaction with BP medications was high.
Cost-effectiveness: A microsimulation model was created to assess costs, clinical outcomes, and quality-adjusted life-years (QALYs) among SPIRIT-eligible adults. The mean number of QALYs was estimated to be 0.27 higher among patients who received intensive control than among those who received standard control and would cost approximately $47,000 more per QALY gained if there were a reduction in adherence and treatment effects after 5 years; the cost would be approximately $28,000 more per QALY gained if the treatment effects persisted for the remaining lifetime of the patient. Most simulation results indicated that intensive treatment would be cost-effective (51-79% below the willingness-to-pay threshold of $50,000 per QALY and 76-93% below the threshold of $100,000 per QALY), regardless of whether treatment effects were reduced after 5 years or persisted for the remaining lifetime.
BP measurement differences: A post hoc survey was conducted at SPRINT closeout sites as to whether BP measurements were usually attended or unattended by staff. Patients were divided into four groups: always alone, never alone, alone for rest, and alone for BP measurement. Improvements in primary endpoint and total mortality with intensive BP lowering were similar between these four groups (p for interaction for primary endpoint = 0.88), suggesting that the results were insensitive to whether or not patient BP measurements were made in an attended fashion.
The results of this landmark trial indicate that intensive BP lowering to a target <120 mm Hg is superior to routine management with a target of <140 mm Hg in high-risk nondiabetic patients with hypertension, including in elderly patients. There were also reductions noted in CV and all-cause mortality, accompanied by a reduction in CHF. An intensive strategy also reduced the risk of developing LVH among patients without baseline LVH and resulted in greater LVH regression among those with evidence of baseline LVH. An intensive strategy carried a higher risk of hypotension, syncope, and accelerated reductions in GFR (only in patients without CKD at baseline). This is a landmark trial and is likely to result in a paradigm shift in the management of patients with hypertension.
The trial design is also interesting because it suggests that hypertension treatment should be individualized based on underlying risk of CV outcomes rather than based on absolute values alone. This change has occurred in lipid management as well, based on the most recent Eighth Joint National Committee (JNC 8) guidelines. The public health importance of this trial will be large. These findings are contrary to the smaller ACCORD trial in patients with diabetes mellitus, where aggressive BP lowering was not associated with superior CV outcomes.
Presented by Dr. Karen C. Johnson at the American Heart Association Annual Scientific Sessions (AHA 2017), Anaheim, CA, November 13, 2017.
Berlowitz DR, Foy CG, Kazis LE, et al., on behalf of the SPRINT Research Group. Effect of Intensive Blood-Pressure Treatment on Patient-Reported Outcomes. N Engl J Med 2017;377:733-44.
Bress AP, Bellows BK, King JB, et al., on behalf of the SPRINT Research Group. Cost-Effectiveness of Intensive versus Standard Blood-Pressure Control. N Engl J Med 2017;377:745-55.
Soliman EZ, Ambrosius WT, Cushman WC, et al., on behalf of the SPRINT Research Study Group. Effect of Intensive Blood Pressure Lowering on Left Ventricular Hypertrophy in Patients with Hypertension: The Systolic Blood Pressure Intervention (SPRINT) Trial. Circulation 2017;136:440-50.
Williamson JD, Supiano MA, Applegate WB, et al., on behalf of the SPRINT Research Group. Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged ≥75 Years: A Randomized Clinical Trial. JAMA 2016;315:2673-82.
The SPRINT Research Group. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med 2015;373:2103-16.
Bress AP, Tanner RM, Hess R, Colantonio LD, Shimbo D, Muntner P. Generalizability of results from the Systolic Blood Pressure Intervention Trial (SPRINT) to the US adult population. J Am Coll Cardiol 2016;67:463-72.
Presented by Dr. Paul K. Whelton at the American Heart Association Scientific Sessions, Orlando, FL, November 9, 2015.
Editorial: Drazen JM, Morrissey S, Campion EW, Jarcho JA. A SPRINT to the Finish. N Engl J Med 2015;373:2174-5.
Editorial: Perkovic V. Redefining Blood-Pressure Targets — SPRINT Starts the Marathon. N Engl J Med 2015;373:2175-8.
Perspective: Chobanian AV. Time to Reassess Blood-Pressure Goals. N Engl J Med 2015;373:2093-5.
Clinical Decisions: Yeh J. Blood Pressure Control. N Engl J Med 2015;373:2180-2.
Study Design: Ambrosius WT, Sink KM, Foy CG, et al., on behalf of the SPRINT Study Research Group. The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: the Systolic Blood Pressure Intervention Trial (SPRINT). Clin Trials 2014;11:532-46.
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