SPRINT Trials: Update From ASH

May 23, 2016

Will more aggressive BP control reduce the risk of CV outcomes? Finally, some answers.

The SPRINT trial is a multi-center, randomized controlled trial sponsored by the National Institutes of Health (NIH) and aimed to answer the following question: “Will more aggressive BP control to SBP <120 mm Hg (intensive group) reduce the risk of cardiovascular, kidney, and cognitive outcomes, compared to the current standard practice of BP control to SBP <140 mm Hg (standard group)?”

The study enrolled 9361 volunteers aged 50 and above, with established cardiovascular disease or with cardiovascular risk factors, with particular emphasis on patients with chronic kidney disease (CKD) with estimated glomerular filtration rate (GFR) of 20-50 mL/min/1.73 m2 and patients aged 75 years and older. Patients with diabetes, stroke, or polycystic kidney disease were not  included in the study (as other studies aimed to answer the question in these patients). The primary outcome was the first occurrence of a myocardial infarction, acute coronary syndrome, stroke, heart failure, or cardiovascular disease death. Secondary outcomes included all-cause mortality, decline in kidney function or development of end stage renal disease, decline in cognitive function and small vessel cerebral ischemic disease.

The median follow up period of the study was 3.2 years, average age of study participants was 68 years, about 36% were female and 30% were of Black ethnicity. 28% of the participants were above the age of 75 years, and 28% had baseline CKD (9.5% of participants had an estimated GFR of less than 45 mL/min/1.73 m2).

The primary results from SPRINT indicate there was a significant 30% lower incidence for primary outcome and a 25% lower risk of death in participants in the intensive group compared to the standard group. The lower incidence for primary outcome was primarily driven by a reduction in heart failure. The benefits extended to the elderly above the age of 75 and in those with CKD. Adverse events, including hypotension, syncope, hyponatremia, and acute kidney injury, was more common in the intensive group. Renin angiotensin system (RAS) blockers were the most common medication class used in both groups. Chlorthalidone was the preferred diuretic of choice in the study. Based on the NHANES data from 2007 – 2012, it is estimated that 7.6% or 16.8 million US adults would meet eligibility criteria for SPRINT. Other study results including cognitive outcomes are still awaited, as are more details on long term renal function.

Data on outcomes and adverse events in the frail elderly (compared to the fit elderly above the age of 75 years) (SPRINT SENIOR) are expected to be published soon. Preliminary results from the SPRINT ABPM sub-study (where a subset of patients had 24 hr ambulatory blood pressure measurements done in addition to office BP) indicate that the intensive group had lower average daytime, nighttime, and 24 hour blood pressures compared to the standard group, with lower blood pressure variability. Updated analysis of heart failure events (SPRINT HF sub-study) again showed significant differences between the intensive and standard group, with a 36% reduction of acute decompensated heart failure events in the former group. Further analysis of heart failure events with preserved versus reduced ejection fraction is awaited, as are analyses of medications – there was more use of all medication groups within the intensive group, including medications which would drive heart failure benefit (renin angiotensin system blockers, beta blockers, diuretics, and aldosterone antagonists). 

What should we do?

  • Emphasize correct BP measurement in office.

  • Emphasize lifestyle modifications in patients with hypertension, including a low sodium DASH (Dietary Approaches to Stop Hypertension) diet, physical activity, weight management, and moderation in alcohol intake.

  • Individualize treatment – the SPRINT results apply to “SPRINT-like” patients, that is, patients without a history of diabetes and stroke, and office BP was taken according to strict guidelines with an automated oscillometric BP monitor (3 readings taken at 1 minute intervals with patient alone in the room, with a 5 minute period of rest prior to measurement)

  • Keep in mind that the intensive group in the SPRINT trial was followed very closely – if intensifying treatment in the “real world”, close follow-up including frequent lab assessments to check renal function and electrolytes, may be needed.

  • The risks and benefits of intensive control will need to be balanced in individual patients, especially considering the higher incidence of adverse events in the intensive group.

  • Further results on quality of life measures, cognitive outcomes, experience in the elderly (especially the frail elderly), and long term renal outcomes, are awaited – this can further inform decisions about managing these patients, with a better understanding potential benefits and risks

  • The American Heart Association and the American College of Cardiology are in the process of formulating new hypertension guidelines, and evidence from the SPRINT trial will inform any new recommendations.