The SPRINT Trial: Pros
Editor's Note: This is Part I (Pros) of a two-part Expert Analysis. Go to Part II (Cons).
The Systolic Blood Pressure Intervention Trial (SPRINT) was designed to test the hypothesis that systolic blood pressure (SBP) reduction to a goal of less than 120 mm Hg had a greater impact on fatal and non-fatal cardiovascular events than reducing SBP to the goal of <140 mm Hg,1 the current guideline recommendation in the U.S. and Europe for persons <60 years old and those with chronic kidney disease (CKD) and diabetes mellitus (DM).2,3 Although these SBP goals were similar to those in the BP-lowering arm of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial that enrolled only patients with diabetes,4 SPRINT enrolled considerably more hypertensive patients ≥50 years old without diabetes (n = 9,361) who were at increased cardiovascular risk because of pre-existing cardiovascular disease (CVD), CKD stage II-III, age >75 years, or a Framingham 10-year CVD risk score of ≥15%.5 At screening, persons with SBP >180 mm Hg; those taking four or more medications; those with diabetes, dementia, prior stroke, or TIA; or significant albuminuria were excluded from participating. At the recommendation of the Data Safety and Quality Monitoring Board, the trial was halted after only 3.26 years average follow-up because of a 25% relative risk reduction in the primary composite endpoint (95% confidence interval [CI] 0.64-0.89, P <0.001) and a 27% reduction in all-cause mortality (95% CI 0.6-0.9; P <0.003) in the cohort assigned to intensive SBP reduction (mean SBP 121.4 mm Hg) compared to those in the standard SBP treatment group (mean SBP 136.2 mm Hg). The benefits of intensive SBP reduction were observed in all pre-specified subgroups, including those with CVD and CKD, and the elderly. Intensive blood pressure treatment was associated with a 38% reduction in the development of heart failure (P <0.002) and a 43% reduction in death from cardiovascular causes (P <0.005). The observation that death from any cause was also significantly reduced in the intensive treatment group is unexplained. It is also somewhat surprising that intensive treatment did not lower the risk of stroke, myocardial infarction, or acute coronary syndrome.
It has been estimated that as many as 16 million Americans have clinical characteristics similar to those required for enrollment in SPRINT and could potentially derive benefit from achievement of lower BPs than those recommended in current guidelines.6 Surprisingly, cardiovascular risk reduction during intensive BP treatment was particularly robust in elderly patients. However, as both autonomic function and renal function decline with advancing age, processes exaggerated by hypertension, the likelihood of experiencing orthostatic hypotension, acute kidney injury, or electrolyte abnormalities such as hyponatremia, hypokalemia, hyperkalemia increases. In addition, intensive BP control required on average one more antihypertensive drug in SPRINT than was needed in the standard treatment group. Thus, patients in the intensive treatment group had more serious adverse effects, including orthostatic hypotension, syncope, and electrolyte abnormalities than did those in the standard treatment group. Patients in clinical practice treated to a similar goal will need to be monitored carefully for the development of these adverse effects. A higher number of medications needed to treat to lower BP goals also has health care cost implications. A health care cost analysis was pre-specified when the SPRINT protocol was developed. Publications of analyses of adverse events and their associated costs by selected subgroups, such as the elderly, should be useful for the practice community to consider when making decisions about treating high-risk hypertensive patients similar to those enrolled in SPRINT.
- Ambrosius WT, Sink KM, Foy CG, et al. 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.
- James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014;311:507-20.
- Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2013;31:1281-357.
- Cushman WC, Evans GW, Byington RP, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010;362:1575-85.
- SPRINT Research Group, Wright JT Jr, Williamson JD, et al. 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 2015 Oct 31. [Epub ahead of print]
- Valbusa F, Labat C, Salvi P, Vivian ME, Hanon O, Benetos A. Orthostatic hypotension in very old individuals living in nursing homes: the PARTAGE study. J Hypertens 2012;30:53-60.
< Back to Listings