SPRINT 2015

Methods	Multicentre, randomized, parallel, controlled trial. Blinded to the outcomes assessor. The intervention was stopped early after a median follow‐up of 3.26 years
Participants	Men and women aged ≥50 years and SBP 130 to 180 mmHg (on 0 or 1 medication), 130 to 170 mmHg (on up to 2 medications), 130 to 160 mmHg (on up to 3 medications) or 130 to 150 mmHg (on up to 4 medications). Participants also had at least one of the following risk factors: presence of clinical or subclinical CVD other than stroke; CKD; Framingham risk score for 10 year CVD risk 15%; or aged ≥75 years. Two major exclusion criteria: diabetes mellitus and stroke. Other exclusion criteria were secondary hypertension, proteinuria, recent cardiovascular event or procedure, and symptomatic heart failure within the past 6 months
Interventions	Standard target: SBP < 140 mmHg Intensive target: SBP < 120 mmHg
Outcomes	The primary outcome was a composite of non fatal MI, acute coronary syndrome not resulting in MI, non fatal stroke, non fatal acute decompensated heart failure, and death from cardiovascular disease. Three subgroups were of particular interest: participants with and without CKD, Black or non Black participants, and participants aged < or ≥75 years. SPRINT prespecified secondary outcomes included components of the primary outcome, total mortality, and a composite of the primary outcome (i.e. cardiovascular disease‐free survival). Additional secondary cardiovascular disease outcomes included peripheral arterial disease, coronary revascularization, TIA, left ventricular hypertrophy (LVH) on ECG, and atrial fibrillation or flutter. Peripheral arterial disease included carotid and peripheral revascularization, abdominal aortic aneurysm repair and other objectively defined peripheral arterial disease events
Funding sources	Federal funds from the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging and the National Institute of Neurological Disorders and Stroke
Declarations of interest	The study authors declared no conflicts of interest (In Clinical Trials 2014;11(5):532–46) In NEJM 2015;26;373(22):2103‐16, Dr. Ambrosius, Dr. Johnson, Dr. Rahman, Dr. Reboussin, Dr. Rocco, Dr. Sink, Dr. Williamson and Dr. Wright, Jr. report grant support from NIH/NHLBI and non‐financial support from Takeda Pharmaceuticals International, Inc, and Arbor Pharmaceuticals, LLC, during the conduct of the study. Dr. Cheung and Dr. Goff report grant support from the National Institutes of Health during the conduct of the study. Dr. Cushman reports grant support from the National Institutes of Health (NIH) and non‐financial support from Takeda Pharmaceuticals International, Inc., and Arbor Pharmaceuticals, LLC, during the conduct of the study; and personal fees from Takeda and Novartis outside the submitted work. Dr. Cutler reports non‐financial support from Takeda International Pharmaceuticals Inc. and Arbor Pharmaceuticals, Inc., during the conduct of the study, and personal fees from the National Heart, Lung, and Blood Institute outside the submitted work. Dr. Fine, Ms. Snyder and Dr. Whelton report non‐financial support from Takeda Pharmaceuticals International, Inc., and Arbor Pharmaceuticals, LLC, during the conduct of the study. Dr. Kimmel reports personal fees from Academic Press outside the submitted work. Dr. Lewis reports grant support from the NIH and non‐financial support from Takeda Pharmaceuticals International and Arbor Pharmaceuticals during the conduct of the study; and grant support from Novo Nordisk outside the submitted work. Dr. Oparil reports grant support from the NIH/NHLBI during the conduct of the study; grant support from Merck and Co., the NIH/NHLBI, Novartis, and Arbor Pharmaceuticals, LLC, grant support and personal fees from AstraZeneca and Bayer, grant support, personal fees and non‐financial support from Medtronic, and personal fees from Forest Laboratories, Inc., Amgen (Onyx – Subsidiary), Boehringer Ingelheim, and GlaxoSmithKline outside the submitted work. In addition, Dr. Oparil was co‐chair (JNC 8): "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), and Co‐Chair, 2007‐2013 (JAMA 311(5):507‐520, 2014).
Notes	Four institutes of the National Institutes of Health (NIH) co‐sponsored SPRINT. The authors declared no conflicts of interest. A public repository provided individual patient data for hypertensive participants with established cardiovascular disease for use in this Cochrane Review
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Participant randomization: SPRINT will use an internet‐based, web browser randomisation procedure. Clinical Sites access the randomisation application through the study web site. Access to this application is password protected and its communications are encrypted. Once security requirements are satisfied, a series of questions identify and verify the eligibility of the participant. When the session is complete, an e‐mail is sent to the Clinic Coordinator, the appropriate CCN, and the CC indicating that the participant has been properly randomised and appended to the database" (pp. 2103‐16)
Allocation concealment (selection bias)	Unclear risk	No detailed information was provided on the randomization system used in the trial
Blinding of participants and personnel (performance bias) All outcomes	High risk	The study design was not compatible with blinding of participants and personnel
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"Participants and study personnel were aware of the study‐group assignments, but outcome adjudicators were not" (pp. 2103‐16)
Incomplete outcome data (attrition bias) All outcomes	Low risk	No attrition bias detected (pp. 2103‐16, Figure 1)
Selective reporting (reporting bias)	Low risk	No reporting bias detected (protocol checked)
Other bias	High risk	Only about 17% of total participants met review inclusion criteria (participants with established cardiovascular disease). The trial was assessed as biased because it was stopped early for benefit