Interpreting Key Trials

Interpreting SPRINT: How low should you go?

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ABSTRACTThe Systolic Blood Pressure Intervention Trial (SPRINT) found evidence of cardiovascular benefit with intensive lowering of systolic blood pressure (goal < 120 mm Hg) compared with the currently recommended goal (< 140 mm Hg) in older patients with cardiovascular risk but without diabetes or stroke. This article reviews the trial design and protocol, summarizes the results, and briefly discusses the implications of these results.


  • SPRINT is the first large prospective randomized trial to show evidence of cardiovascular and mortality benefit for intensive lowering of systolic blood pressure (goal < 120 mm Hg) in older patients at cardiovascular risk, but without a history of diabetes mellitus or stroke.
  • A similar trial in patients with type 2 diabetes mellitus did not show significant benefit of intensive treatment.
  • Intensive treatment was associated with more adverse events, including hypotension, syncope, electrolyte abnormalities, and acute kidney injury.
  • It is unclear if these results can be extrapolated to patients with a history of diabetes or stroke, younger patients, or those with low cardiovascular risk.
  • Healthcare providers should engage patients in a shared decision-making process, with discussion of the benefits and risks associated with intensive lowering of blood pressure.



In treating hypertension, lower systolic pressure is better than higher—with caveats. This is the message of the Systolic Blood Pressure Intervention Trial (SPRINT),1 a large, federally funded study that was halted early when patients at high cardiovascular risk who were randomized to a goal systolic pressure of less than 120 mm Hg were found to have better outcomes, including lower rates of heart failure, death from cardiovascular causes, and death from any cause, than patients randomized to a goal of less than 140 mm Hg.

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The caveats: the benefit came at a price of more adverse events. Also, the trial excluded patients who had diabetes mellitus or previous strokes, so it is uncertain if these subgroups would also benefit from intensive lowering of systolic pressure—and in earlier trials they did not.

This article reviews the trial design and protocol, summarizes the results, and briefly discusses the implications of these results.


Hypertension is very common in adults in the United States, and is a risk factor for heart disease, stroke, heart failure, and kidney disease. The estimated prevalence of hypertension in the 2011–2014 National Health and Nutrition Examination Survey (NHANES) was 29%, and the prevalence increases with age (7.3% in those ages 18 to 39, 32.2% in those ages 40 to 59, and 64.9% in those ages 60 and older).2 Isolated systolic hypertension (ie, systolic blood pressure > 140 mm Hg with diastolic pressure < 90 mm Hg) is the most common form of hypertension after age 50.3

Clinical trials have provided substantial evidence that treating hypertension reduces the incidence of stroke, myocardial infarction, and heart failure.4,5 Although observational studies show a progressive and linear rise in cardiovascular risk as systolic blood pressure rises above 115 mm Hg,6 clinical trials in the general population have not documented benefits of lowering systolic pressure to this level.7–11 However, clinical trials that directly evaluated two different blood pressure goals in the general population showed benefit with achieving systolic blood pressure less than 150 mm Hg,7,9 with limited data on lower blood pressure targets.10–12

No benefit found in intensive systolic lowering in diabetes or after stroke

The Action to Control Cardiovascular Risk in Diabetes-Blood Pressure (ACCORD BP) trial13 in patients with type 2 diabetes found no benefit in lowering systolic pressure to less than 120 mm Hg compared with less than 140 mm Hg in terms of the trial’s primary composite cardiovascular outcome (ie, nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes). However, the intensively treated group in this trial did enjoy a benefit in terms of fewer stroke events.

The Secondary Prevention of Small Subcortical Strokes (SPS3) trial14 in patients with stroke found no significant benefit in lowering systolic pressure to less than 130 mm Hg compared with less than 150 mm Hg for overall risk of another stroke, but a significant benefit was noted in reduced risk of intracerebral hemorrhage.

Current guidelines, based on available evidence, advocate treatment to a systolic goal of less than 140 mm Hg in most patients, and recommend relaxing this goal to less than 150 mm Hg in the elderly.15,16

SPRINT was stopped early due to better outcomes in the intensive treatment group

Given the uncertainty surrounding optimal systolic targets, SPRINT was designed to test the hypothesis that a goal of less than 120 mm Hg would reduce the risk of cardiovascular events more than the generally accepted systolic goal of less than 140 mm Hg.17 Patients with diabetes and stroke were excluded because a similar hypothesis was tested in the ACCORD BP and SPS3 trials, which included patients with these conditions.


SPRINT was a randomized, controlled, open-label trial sponsored by the National Institutes of Health and conducted at 102 US sites.

Inclusion criteria. Participants had to be at least 50 years old, with systolic pressure of 130 to 180 mm Hg, and had to have at least one cardiovascular risk factor, eg:

  • Clinical or subclinical cardiovascular disease (other than stroke)
  • Chronic kidney disease, defined as estimated glomerular filtration rate (eGFR), calculated by the Modification of Diet in Renal Disease (MDRD) study equation, of 20 to less than 60 mL/min/1.73 m2
  • Framingham risk score of 15% of more
  • Age 75 or older.

Major exclusion criteria included:

  • Diabetes
  • Stroke
  • Polycystic kidney disease
  • Chronic kidney disease with an eGFR less than 20 mL/min/1.73 m2
  • Proteinuria (excretion > 1 g/day).

Intensive vs standard treatment

Participants were randomized to receive intensive treatment (systolic goal < 120 mm Hg) or standard treatment (systolic goal < 140 mm Hg). Baseline antihypertensive medications were adjusted to achieve blood pressure goals based on randomization assignment.

Doses of medications were adjusted on the basis of an average of three seated office blood pressure measurements after a 5-minute period of rest, taken with an automated monitor (Omron Healthcare Model 907); the same monitor was used and the same protocol was followed at all participating sites. Blood pressure was also measured after standing for 1 minute to assess orthostatic change.

Intensive treatment required, on average, one more medication than standard treatment

Lifestyle modifications were encouraged in both groups. There was no restriction on using any antihypertensive medication, and this was at the discretion of individual investigators. Thiazide-type diuretics were encouraged as first-line agents (with chlorthalidone encouraged as the primary thiazide-type diuretic).

Outcomes measured

The primary outcome was a composite of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, and cardiovascular mortality.

Secondary outcomes included individual components of the primary composite outcome, all-cause mortality, and the composite of primary outcome and all-cause mortality.

Renal outcomes were assessed as:

  • Incident albuminuria (doubling of the urinary albumin-to-creatinine ratio from less than 10 mg/g to more than 10 mg/g)
  • Composite of a 50% decrease in eGFR or development of end-stage renal disease requiring long-term dialysis or kidney transplantation (in those with baseline chronic kidney disease)
  • A 30% decrease in eGFR (in those without chronic kidney disease).1,17

SPRINT also recruited participants to two nested substudies: SPRINT MIND and SPRINT MIND MRI, to study differences in cognitive outcomes and small-vessel ischemic disease between intensive treatment and standard treatment.

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