Systolic Blood Pressure Intervention Trial - SPRINT

Description:

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.

Visit ACC.org's SPRINT Trial Hub

Contribution to the Literature: 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.

Study Design

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)

Inclusion criteria:

  • 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

Exclusion criteria:

  • 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
  • Proteinuria
  • 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

Principal Findings:

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 0.75, 95% confidence interval 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.

Interpretation:

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 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.

References:

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;May 19:[Epub ahead of print].

The SPRINT Research Group. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med 2015;Nov 9:[Epub ahead of print].

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 2015;Nov 9:[Epub ahead of print].

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;Nov 9:[Epub ahead of print].

Editorial: Perkovic V. Redefining Blood-Pressure Targets — SPRINT Starts the Marathon. N Engl J Med 2015;Nov 9:[Epub ahead of print].

Perspective: Chobanian AV. Time to Reassess Blood-Pressure Goals. N Engl J Med 2015;Nov 9:[Epub ahead of print].

Clinical Decisions: Yeh J. Blood Pressure Control. N Engl J Med 2015;Nov 9:[Epub ahead of print].

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.

Clinical Topics: Acute Coronary Syndromes, Diabetes and Cardiometabolic Disease, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Hypertension

Keywords: Acute Coronary Syndrome, Blood Pressure, Blood Pressure Determination, Geriatrics, Hypertension, Heart Failure, Metabolic Syndrome X, Myocardial Infarction, Primary Prevention, Renal Insufficiency, Chronic, Risk Factors, Stroke, AHA Annual Scientific Sessions


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