Systolic Blood Pressure Intervention Trial

Systolic Blood Pressure Intervention Trial
Name	Systolic Blood Pressure Intervention Trial
Acronym	SPRINT
Phase	Randomized controlled trial
Status	Completed
Locations	United States
Sponsor	National Institutes of Health
Participants	9361
Start date	2010
Primary completion date	2015

Systolic Blood Pressure Intervention Trial The Systolic Blood Pressure Intervention Trial was a multicenter randomized controlled trial that tested intensive versus standard systolic blood pressure targets in adults at increased cardiovascular risk. The trial influenced contemporary hypertension guidelines and engaged institutions such as the National Institutes of Health, National Heart, Lung, and Blood Institute, and multiple academic medical centers. Key investigators included clinicians and researchers affiliated with universities, medical centers, and professional organizations across the United States.

Background

The trial was conceived amid debates between proponents of lower systolic targets advocated by clinicians at institutions like Hypertension Canada and guideline panels such as committees convened by the American Heart Association, American College of Cardiology, and the European Society of Cardiology. Rising attention to cardiovascular disease prevention from organizations including the World Health Organization and research networks like the Clinical and Translational Science Awards program prompted the National Heart, Lung, and Blood Institute to fund a large pragmatic trial. Prior landmark studies that framed equipoise included the Framingham Heart Study, the ALLHAT trial, and the HOT trial, while observational evidence from cohorts such as the Cardiovascular Health Study and the Atherosclerosis Risk in Communities Study showed associations between systolic pressure and outcomes.

Study Design and Methods

SPRINT employed an open-label, randomized, controlled design with blinded outcome assessment coordinated through clinical sites associated with academic centers like Johns Hopkins University, University of California, San Francisco, and Brigham and Women's Hospital. Participants were randomized to an intensive treatment arm targeting systolic blood pressure <120 mm Hg or a standard arm targeting <140 mm Hg, with event adjudication by committees modeled on methods used in trials such as the HOT trial and ALLHAT trial. The trial's statistical analysis plan drew on approaches used in the Framingham Heart Study and techniques described by investigators linked to the Duke Clinical Research Institute, ensuring power to detect differences in a composite primary outcome of myocardial infarction, acute coronary syndrome, stroke, heart failure, or cardiovascular death.

Participant Characteristics

The cohort comprised older adults recruited from primary care networks and specialty clinics affiliated with institutions including University of Pennsylvania, Vanderbilt University Medical Center, and Mayo Clinic. Enrollment criteria emphasized age ≥50 years with increased cardiovascular risk, excluding individuals with diabetes or prior stroke to reduce heterogeneity compared with trials like ACCORD and PROGRESS. Demographic representation included participants from urban centers such as Boston, Chicago, and Los Angeles, as well as rural sites in partnership with networks resembling the Clinical and Translational Science Awards hubs. Baseline comorbidities mirrored prevalences seen in cohorts like the Cardiovascular Health Study.

Interventions and Treatment Protocols

Treatment algorithms used antihypertensive agents from classes championed in trials like ALLHAT and clinical guidelines from the American College of Cardiology and American Heart Association. First-line agents included thiazide-type diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers, with adjustments overseen by site investigators at centers such as University of Michigan and Yale School of Medicine. Medication titration, visit frequency, and monitoring protocols paralleled strategies used in pragmatic trials coordinated by networks like the Duke Clinical Research Institute and trial infrastructures supported by the National Institutes of Health.

Outcomes and Results

The primary composite cardiovascular outcome showed fewer events in the intensive-treatment arm, consistent with declines in outcomes targeted in prior studies like Framingham Heart Study-derived risk models. Secondary analyses demonstrated reductions in all-cause mortality and heart failure incidence, prompting rapid reinterpretation of guideline targets by organizations including the American College of Cardiology and American Heart Association. Subgroup assessments explored heterogeneity across age groups including adults aged ≥75 years, mirroring analyses comparable to cohorts from the Cardiovascular Health Study.

Adverse Events and Safety

Intensive treatment was associated with higher rates of some adverse events monitored through safety committees modeled on procedures used in ALLHAT and other NHLBI trials. Reported issues included events such as hypotension, syncope, electrolyte abnormalities, and acute kidney injury, requiring adjudication analogous to processes employed by the Duke Clinical Research Institute and safety oversight by boards akin to those convened by the National Institutes of Health.

Interpretation and Impact

Results accelerated shifts in hypertension targets advocated by guideline bodies like the American College of Cardiology and American Heart Association and influenced statements from professional societies including the International Society of Hypertension and the European Society of Cardiology. Health systems and payers, including entities resembling Centers for Medicare & Medicaid Services, evaluated implications for performance metrics derived from earlier initiatives such as the Million Hearts program. The trial stimulated further research networks and secondary analyses from academic centers including Johns Hopkins University and Mayo Clinic.

Criticisms and Limitations

Critiques addressed trial generalizability to populations excluded for conditions such as diabetes or stroke, comparing applicability to trials like ACCORD and PROGRESS. Observers noted intensive monitoring and visit frequency at centers like Brigham and Women's Hospital may limit real-world implementation, and concerns were raised about risk-benefit trade-offs in frail elderly subgroups represented in cohorts such as the Cardiovascular Health Study. Methodological discussions referenced guideline panels from the American Heart Association and analytic considerations familiar to investigators at the Duke Clinical Research Institute.

Category:Clinical trials