Principal Findings:

The trial was terminated early due to overwhelming evidence of benefit. The primary outcome, myocardial infarction (MI), acute coronary syndrome (ACS), stroke, congestive heart failure (CHF), or cardiovascular (CV) death, was significantly lowered in the intensive BP management arm compared with the routine management arm (5.2% vs. 6.8%, hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.64–0.89; p < 0.0001).

Individual components (event rates for intensive vs. routine management, absolute event rates):

• MI: 2.1% vs. 2.5%, p = 0.19
• ACS: 0.9% vs. 0.9%, p = 0.99
• Stroke: 1.3% vs. 1.5%, p = 0.5
• CHF: 1.3% vs. 2.1%, p = 0.002
• CV death: 0.8% vs. 1.4%, p = 0.0005

Important secondary endpoints for intensive vs. routine BP control, absolute event rates:

• Mortality: 3.3% vs. 4.5%, p = 0.0003
• Among patients with chronic kidney disease: composite renal endpoint (decrease in GFR ≥50%, need for HD, renal transplant); 1.1% vs. 1.1%, p = 0.76
• Among patients without CKD: ≥30% decline in GFR to <60 ml/min: 3.8% vs. 1.1%, p < 0.001
• Hypotension: 2.4% vs. 1.4%, p = 0.001
• Syncope: 2.3% vs. 1.7%, p = 0.05
• Hyponatremia: 3.8% vs. 2.1%, p < 0.001

Generalizability to the US population: Based on National Health and Nutrition Examination Survey (NHANES) data from 2007 to 2012, it appears that 7.6% or 16.8 million US adults, and 16.7% or 8.2 million of those with treated hypertension, would meet the SPRINT eligibility criteria. Thus, 8.6 million of US adults are not currently treated for hypertension based on the SPRINT trial, highlighting the public health importance of these findings. 

Among patients aged ≥75 years (n = 2,636), primary outcomes for intensive vs. routine BP management were 7.7% vs. 11.2%, p < 0.05. All-cause mortality was 5.5% vs. 8.1%, respectively, p < 0.05.

Left ventricular hypertrophy (LVH) progression (n = 8,164): Among participants without baseline LVH, intensive BP lowering reduced LVH on electrocardiogram (HR 0.54, 95% CI 0.43-0.68). Similarly, among participants with baseline LVH (n = 605, 7.4%), intensive BP lowering was more likely to show LVH regression (HR 1.66, 95% CI 1.31-2.11). Adjusting for LVH did not attenuate the risk of CV disease (CVD) with intensive lowering, suggesting that LVH improvement was not a significant driver of CVD reduction with intensive BP lowering.

Effect on patient-reported outcomes: Patient-reported outcome measures included the scores on the Physical Component Summary (PCS) and Mental Component Summary (MCS) of the Veterans RAND 12-Item Health Survey, the Patient Health Questionnaire 9-item depression scale (PHQ-9), among others. Participants who received intensive treatment received an average of one additional antihypertensive medication, and the systolic blood pressure was 14.8 mm Hg (95% confidence interval, 14.3-15.4) lower in the group that received intensive treatment than in the group that received standard treatment. Mean PCS, MCS, and PHQ-9 scores were relatively stable over a median of 3 years of follow-up, with no significant differences between the two treatment groups. Satisfaction with BP medications was high.

Cost-effectiveness: A microsimulation model was created to assess costs, clinical outcomes, and quality-adjusted life-years (QALYs) among SPIRIT-eligible adults. The mean number of QALYs was estimated to be 0.27 higher among patients who received intensive control than among those who received standard control and would cost approximately $47,000 more per QALY gained if there were a reduction in adherence and treatment effects after 5 years; the cost would be approximately $28,000 more per QALY gained if the treatment effects persisted for the remaining lifetime of the patient. Most simulation results indicated that intensive treatment would be cost-effective (51-79% below the willingness-to-pay threshold of $50,000 per QALY and 76-93% below the threshold of $100,000 per QALY), regardless of whether treatment effects were reduced after 5 years or persisted for the remaining lifetime.

BP measurement differences: A post hoc survey was conducted at SPRINT closeout sites as to whether BP measurements were usually attended or unattended by staff. Patients were divided into four groups: always alone, never alone, alone for rest, and alone for BP measurement. Improvements in primary endpoint and total mortality with intensive BP lowering were similar between these four groups (p for interaction for primary endpoint = 0.88), suggesting that the results were insensitive to whether or not patient BP measurements were made in an attended fashion.

Role of high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro–B-type natriuretic peptide (NT-proBNP) in risk stratification: Median (25th and 75th percentiles) concentration of hs-cTnT was 9.4 (6.4, 14.1) ng/L with 25.6% having values ≥14 ng/L. Median NT-proBNP was 86 (37, 197) pg/ml with 38.2% having concentrations ≥125 pg/ml. Higher baseline values of hs-cTnT and NT-proBNP were each associated with a greater risk of death, the composite of death and heart failure, and the SPRINT primary composite outcome, with highest risk among those with abnormal levels of both biomarkers.

Outcomes based on predicted risk: Predictive models were created for long-term CVD composite endpoint (c-index 0.71), all-cause mortality (c-index 0.75), and treatment-related side effects (c-index 0.69). The baseline factors that were most strongly associated with a higher risk for the CVD composite outcome were older age, history of CVD, and impaired kidney function. The predicted magnitude of benefit of intensive versus standard treatment in terms of absolute risk reduction grew linearly as baseline risk increased. For instance, the risk of long-term composite CVD events was 2.4% at the 10th percentile and 14% at the 90th percentile. The predicted risks of composite CVD events and treatment-related adverse events (AEs) demonstrated close correlation. Few participants were predicted as high benefit with low AE risk (1.8%) or low benefit with high AE risk (1.5%).