Effect of Intensive Blood Pressure Control on Kidney Outcomes: Long-Term Electronic Health Record-Based Post-Trial Follow-Up of SPRINT.

BACKGROUND: Intensive BP lowering in the Systolic Blood Pressure Intervention Trial (SPRINT) produced acute decreases in kidney function and higher risk for AKI. We evaluated the effect of intensive BP lowering on long-term changes in kidney function using trial and outpatient electronic health record (EHR) creatinine values. METHODS: SPRINT data were linked with EHR data from 49 (of 102) study sites. The primary outcome was the total slope of decline in eGFR for the intervention phase and the post-trial slope of decline during the observation phase using trial and outpatient EHR values. Secondary outcomes included a ≥30% decline in eGFR to <60 ml/min per 1.73 m 2 and a ≥50% decline in eGFR or kidney failure among participants with baseline eGFR ≥60 and <60 ml/min per 1.73 m 2 , respectively. RESULTS: EHR creatinine values were available for a median of 8.3 years for 3041 participants. The total slope of decline in eGFR during the intervention phase was -0.67 ml/min per 1.73 m 2 per year (95% confidence interval [CI], -0.79 to -0.56) in the standard treatment group and -0.96 ml/min per 1.73 m 2 per year (95% CI, -1.08 to -0.85) in the intensive treatment group ( P < 0.001). The slopes were not significantly different during the observation phase: -1.02 ml/min per 1.73 m 2 per year (95% CI, -1.24 to -0.81) in the standard group and -0.85 ml/min per 1.73 m 2 per year (95% CI, -1.07 to -0.64) in the intensive group. Among participants without CKD at baseline, intensive treatment was associated with higher risk of a ≥30% decline in eGFR during the intervention (hazard ratio, 3.27; 95% CI, 2.43 to 4.40), but not during the postintervention observation phase. In those with CKD at baseline, intensive treatment was associated with a higher hazard of eGFR decline only during the intervention phase (hazard ratio, 1.95; 95% CI, 1.03 to 3.70). CONCLUSIONS: Intensive BP lowering was associated with a steeper total slope of decline in eGFR and higher risk for kidney events during the intervention phase of the trial, but not during the postintervention observation phase.

Fluid Intake Management in Maintenance Hemodialysis Using a Smartphone-Based Application: A Pilot Study.

Rationale & Objective: Increased interdialytic weight gain (IDWG) has been associated with increased morbidity and mortality. We evaluated the usefulness and safety of a mobile application (app) that allows patients receiving maintenance hemodialysis to self-monitor their daily fluid intake. Study Design: Within group comparison before or during intervention. Setting & Participants: Patients receiving maintenance hemodialysis with mean IDWG of <4%. Exposure: Participants were trained to use a smartphone-based app, FiApp that allowed them to record fluid intake and compare with individual targeted daily fluid intake determined by the nephrologist. Outcomes: The primary study outcome was the association between IDWG and fluid intake recorded in the FiApp. Secondary outcomes included FiApp safety and usage. Patient interviews were performed at weeks 1 and 4 to collect information regarding FiApp usability and recommendations for app improvements. Analytical Approach: Mean, median, and standard deviation. Results: Eighteen of 25 patients completed the full 4-week study, provided all app data, and completed 2 patient interviews. The mean 4-week IDWG during app use was similar to the baseline mean 4-week IDWG before app use; however, 61% of the participants had a decrease in IDWG when using the app compared with IDWG at baseline. Of the 18 participants who completed the study, only 1 had a mean 4-week IDWG that was 20% higher than that at baseline. The app was used on ≥80% of the days by 13 (72%) of 18 participants, and was used every day in 7 (39%) of 18 participants. The mean relationship between fluid reported in the app and fluid consumed was 40%. Limitations: This safety study recruited patients who had IDWG of <4%. Conclusions: A smartphone-based app can be safely used to help patients receiving maintenance hemodialysis track and control fluid intake. Motivated patients were able to decrease IDWG despite baseline IDWG being <4% of the body weight. Trial Registration: NCT03759847. Plain-Language Summary: Patients receiving maintenance hemodialysis struggle to limit fluid intake. Excess fluid intake can lead to adverse cardiovascular events. We developed a smartphone app to help patients receiving dialysis self-monitor their fluid intake. In this safety study in patients receiving dialysis with an interdialytic weight gain of <4% of the body weight, more than half of the patients were able to decrease their interdialytic fluid intake while using the app, and only 1 patient had an increase in interdialytic weight gain of >20% while using the app. Information gleaned from structured patient interviews will be used to refine this app.

Concordance between clinical outcomes in the Systolic Blood Pressure Intervention Trial and in the electronic health record.

BACKGROUND: Randomized trials are the gold standard for generating clinical practice evidence, but follow-up and outcome ascertainment are resource-intensive. Electronic health record (EHR) data from routine care can be a cost-effective means of follow-up, but concordance with trial-ascertained outcomes is less well-studied. METHODS: We linked EHR and trial data for participants of the Systolic Blood Pressure Intervention Trial (SPRINT), a randomized trial comparing intensive and standard blood pressure targets. Among participants with available EHR data concurrent to trial-ascertained outcomes, we calculated sensitivity, specificity, positive predictive value, and negative predictive value for EHR-recorded cardiovascular disease (CVD) events, using the gold standard of SPRINT-adjudicated outcomes (myocardial infarction (MI)/acute coronary syndrome (ACS), heart failure, stroke, and composite CVD events). We additionally compared the incidence of non-CVD adverse events (hyponatremia, hypernatremia, hypokalemia, hyperkalemia, bradycardia, and hypotension) in trial versus EHR data. RESULTS: 2468 SPRINT participants were included (mean age 68 (SD 9) years; 26% female). EHR data demonstrated ≥80% sensitivity and specificity, and ≥ 99% negative predictive value for MI/ACS, heart failure, stroke, and composite CVD events. Positive predictive value ranged from 26% (95% CI; 16%, 38%) for heart failure to 52% (95% CI; 37%, 67%) for MI/ACS. EHR data uniformly identified more non-CVD adverse events and higher incidence rates compared with trial ascertainment. CONCLUSIONS: These results support a role for EHR data collection in clinical trials, particularly for capturing laboratory-based adverse events. EHR data may be an efficient source for CVD outcome ascertainment, though there is clear benefit from adjudication to avoid false positives.

Medical Information Delivering Improved Customer Experience: A Guide.

Customer experience (CX) is essential in any business. In the pharmaceutical industry, the Medical Information Contact Center is a customer-facing unit that provides evidence-based, scientifically balanced information to healthcare professionals and patients in response to unsolicited inquiries. The purpose of this paper is to provide analysis and guidance for designing and measuring interactions in the Medical Information Contact Center to facilitate the delivery of a superior and continuously improving CX. Surveys were conducted to establish current trends in CX among a diverse group of CX professionals and members of phactMI, a non-profit collaboration of Medical Information leaders from the pharmaceutical industry. The top three observations from the CX professionals survey centered on establishing a clear CX strategy, use of technology, and frequency of sharing results. Three potential areas for improvement focus on CX strategy, measurements of CX, and sharing of results. An analysis of quality monitoring results of customer interactions in the pharmaceutical industry from Centerfirst, a contact center quality monitoring service provider, was also reviewed. This analysis found a positive correlation between CX and three agent skills: taking the lead, empathy, and strong compliance skills. Based on these results, a CX guide was developed and specifically tailored for the pharmaceutical industry. This tool may be used to help identify, assess, and possibly improve CX.

Efficient Recovery of Organic Matter from Municipal Wastewater by a High-Rate Membrane Bioreactor Equipped with Flat-Sheet Ceramic Membranes.

High-rate processes have been investigated for the recovery of organic matter from municipal wastewater. High-rate membrane bioreactors (HR-MBRs) may simultaneously achieve the increased recovery of carbon and high effluent quality, although control of membrane fouling is extremely difficult. To address the severe fouling in HR-MBRs, the combination of granular scouring and frequent chemically enhanced backwashing was examined. The use of robust flat-sheet ceramic membranes enabled the application of those cleaning strategies. Experiments were carried out at an existing wastewater treatment plant. To operate as a high-rate system, the bioreactor solid residence time and hydraulic residence time were set at 0.5 days and 1.6 h, respectively. Although a relatively high flux of 20 L m-2 h-1 was applied, the proposed HR-MBR exhibited a very low fouling rate of 1.3 kPa/day. The system could recover >70% of the carbon from raw wastewater, whereas the concentration of chemical oxygen demand in the effluent was lowered to <20 mg/L. The performance of the proposed HR-MBR observed in this study was clearly superior to those reported in previous related studies.

A National Registry for People With All Stages of Kidney Disease: The National Kidney Foundation (NKF) Patient Network.

RATIONALE & OBJECTIVE: The National Kidney Foundation (NKF) launched the first national US kidney disease patient registry, the NKF Patient Network, that is open to patients throughout the continuum of chronic kidney disease (CKD). The Network provides individualized education and will facilitate patient-centered research, clinical care, and health policy decisions. Here, we present the overall design and the results of a feasibility study that was conducted July through December 2020. STUDY DESIGN: Longitudinal observational cohort study of patient-entered data with or without electronic health care record (EHR) linkage in collaboration with health systems. SETTING & PARTICIPANTS: People with CKD, age≥18 years, are invited through their provider, NKF communications, or national outreach campaign. People self-enroll and share their data through a secure portal that offers individualized education and support. The first health system partner is Geisinger. EXPOSURE: Any cause and stage of CKD, including dialysis and kidney transplant recipients. OUTCOME: Feasibility of the EHR data transfer, participants' characteristics, and their perspectives on usability and content. ANALYTICAL APPROACH: Data were collected and analyzed through the registry portal powered by the Pulse Infoframe healthie 2.0 platform. RESULTS: During the feasibility study, 80 participants completed their profile, and 42 completed a satisfaction survey. Mean age was 57.5 years, 51% were women, 83% were White, and 89% were non-Hispanic or Latino. Of the participants, 60% were not aware of their level of estimated glomerular filtration rate and 91% of their urinary albumin-creatinine ratio. LIMITATIONS: Challenges for the Network are lack of awareness of kidney disease for many with CKD, difficulty in recruiting vulnerable populations or those with low digital readiness, and loss to follow-up, all leading to selection bias. CONCLUSIONS: The Network is positioned to become a national and international platform for real-world data that can inform the development of patient-centered research, care, and treatments.

Longer-Term All-Cause and Cardiovascular Mortality With Intensive Blood Pressure Control: A Secondary Analysis of a Randomized Clinical Trial.

Importance: The Systolic Blood Pressure Intervention Trial (SPRINT) showed that intensive blood pressure control reduced cardiovascular morbidity and mortality. However, the legacy effect of intensive treatment is unknown. Objective: To evaluate the long-term effects of randomization to intensive treatment with the incidence of cardiovascular and all-cause mortality approximately 4.5 years after the trial ended. Design, Setting, and Participants: In this secondary analysis of a multicenter randomized clinical trial, randomization began on November 8, 2010, the trial intervention ended on August 20, 2015, and trial close-out visits occurred through July 2016. Patients 50 years and older with hypertension and increased cardiovascular risk but without diabetes or history of stroke were included from 102 clinic sites in the US and Puerto Rico. Analyses were conducted between October 2021 and February 2022. Interventions: Randomization to systolic blood pressure (SBP) goal of less than 120 mm Hg (intensive treatment group; n = 4678) vs less than 140 mm Hg (standard treatment group; n = 4683). Main Outcomes and Measures: Extended observational follow-up for mortality via the US National Death Index from 2016 through 2020. In a subset of 2944 trial participants, outpatient SBP from electronic health records during and after the trial were examined. Results: Among 9361 randomized participants, the mean (SD) age was 67.9 (9.4) years, and 3332 (35.6%) were women. Over a median (IQR) intervention period of 3.3 (2.9-3.9) years, intensive treatment was beneficial for both cardiovascular mortality (hazard ratio [HR], 0.66; 95% CI, 0.49-0.89) and all-cause mortality (HR, 0.83; 95% CI, 0.68-1.01). However, at the median (IQR) total follow-up of 8.8 (8.3-9.3) years, there was no longer evidence of benefit for cardiovascular mortality (HR, 1.02; 95% CI, 0.84-1.24) or all-cause mortality (HR, 1.08; 95% CI, 0.94-1.23). In a subgroup of participants, the estimated mean outpatient SBP among participants randomized to intensive treatment increased from 132.8 mm Hg (95% CI, 132.0-133.7) at 5 years to 140.4 mm Hg (95% CI, 137.8-143.0) at 10 years following randomization. Conclusions and Relevance: The beneficial effect of intensive treatment on cardiovascular and all-cause mortality did not persist after the trial. Given increasing outpatient SBP levels in participants randomized to intensive treatment following the trial, these results highlight the importance of consistent long-term management of hypertension. Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

Effect of Intensive versus Standard BP Control on AKI and Subsequent Cardiovascular Outcomes and Mortality: Findings from the SPRINT EHR Study.

Background: Adjudication of inpatient AKI in the Systolic Blood Pressure Intervention Trial (SPRINT) was based on billing codes and admission and discharge notes. The purpose of this study was to evaluate the effect of intensive versus standard BP control on creatinine-based inpatient and outpatient AKI, and whether AKI was associated with cardiovascular disease (CVD) and mortality. Methods: We linked electronic health record (EHR) data from 47 clinic sites with trial data to enable creatinine-based adjudication of AKI. Cox regression was used to evaluate the effect of intensive BP control on the incidence of AKI, and the relationship between incident AKI and CVD and all-cause mortality. Results: A total of 3644 participants had linked EHR data. A greater number of inpatient AKI events were identified using EHR data (187 on intensive versus 155 on standard treatment) as compared with serious adverse event (SAE) adjudication in the trial (95 on intensive versus 61 on standard treatment). Intensive treatment increased risk for SPRINT-adjudicated inpatient AKI (HR, 1.51; 95% CI, 1.09 to 2.08) and for creatinine-based outpatient AKI (HR, 1.40; 95% CI, 1.15 to 1.70), but not for creatinine-based inpatient AKI (HR, 1.20; 95% CI, 0.97 to 1.48). Irrespective of the definition (SAE or creatinine based), AKI was associated with increased risk for all-cause mortality, but only creatinine-based inpatient AKI was associated with increased risk for CVD. Conclusions: Creatinine-based ascertainment of AKI, enabled by EHR data, may be more sensitive and less biased than traditional SAE adjudication. Identifying ways to prevent AKI may reduce mortality further in the setting of intensive BP control.

Impact of DBP on all-cause and cardiovascular mortality: results from the National Health and Nutrition Examination survey, 1999-2014.

INTRODUCTION: Hypertension is common and has a significant effect on cardiovascular morbidity and death. However, despite the development of several guidelines to manage SBP, there is little research or guidance on the evaluation and management of DBP or isolated diastolic hypertension (IDH). METHOD: To determine the association of DBP with all-cause and cardiovascular mortality, we used NHANES data from 1999 to 2014 and included adults aged at least 18 years. The relationship between DBP, IDH and all-cause, cardiovascular mortality was evaluated. RESULTS: Of the 35 109 participants, all-cause death occurred in 10.6%, and cardiovascular death occurred in 2.1% over a median follow-up of 7.2 years. Multivariate Cox regression analysis revealed that the risk of all-cause mortality was significantly higher in the lowest (≤56.9 mmHg) DBP groups than in the reference group (DBP 74-76.9 mmHg). However, the risk of cardiovascular mortality was significantly higher in the lowest and highest (≥83 mmHg) DBP group than in the reference group. The risk of all-cause mortality was higher for most groups with SBP at least 140 mmHg than for the reference group with DBP 74-76.9 mmHg and SBP 100-139.9 mmHg. Both the 2018 ESC/NICE and the 2017 AHA/ACC-defined IDH was not significantly associated with all-cause mortality. CONCLUSION: DBP and all-cause mortality had an inverse relationship, whereas DBP and cardiovascular mortality had a U-shaped relationship, with the DBP reference group having the lowest risk for all-cause and cardiovascular mortality. There was no significant relationship between IDH and death.

Is Medication Adherence Predictive of Cardiovascular Outcomes and Blood Pressure Control? The Systolic Blood Pressure Intervention Trial (SPRINT).

BACKGROUND: Adherence to study medications is crucial to evaluating treatment effects in clinical trials. To assess whether in the SPRINT trial, adherence and cardiovascular outcomes are associated regardless of intervention assignment. METHODS: This study included 9,361 participants aged ≥50 years, recruited from 102 clinics. Participants were randomized to a Standard Treatment Group (targeted systolic blood pressure [SBP] <140 mm Hg) or an Intensive Treatment Group (targeted SBP <120 mm Hg) and followed for incident cardiovascular events until the study was halted early for benefit. The 8-item Morisky Medication Adherence Scale (MMAS-8) was administered at baseline, and at the 12- and 48-month (or close out) visit. RESULTS: Adjusting for covariates, there was no association between the baseline 8-item MMAS-8 and the likelihood of the primary composite endpoint, any of the secondary endpoints, or blood pressure (BP) control. Low adherence was associated with a higher body mass index, SBP, diastolic BP, and Patient Health Questionnaire, and high adherence was associated with a higher Montreal Cognitive Assessment. There was no difference in the MMAS-8 over time by treatment arm assignment. For the primary outcome (a composite of myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes), baseline odds ratios (95% confidence intervals) for the Low vs. Medium and vs. High; and, for Medium vs. High MMAS-8 were 1.02 (0.82-1.28), 1.07 (0.85-1.34), and 1.05 (0.88-1.250). CONCLUSIONS: In SPRINT, medication adherence as measured using the MMAS-8 was not associated with outcomes or BP control.

Incidence and Outcomes of Acute Heart Failure With Preserved Versus Reduced Ejection Fraction in SPRINT.

BACKGROUND: In the SPRINT (Systolic Blood Pressure Intervention Trial), intensive BP treatment reduced acute decompensated heart failure (ADHF) events. Here, we report the effect on HF with preserved ejection fraction (HFpEF) and HF with reduced EF (HFrEF) and their subsequent outcomes. METHODS: Incident ADHF was defined as hospitalization or emergency department visit, confirmed, and formally adjudicated by a blinded events committee using standardized protocols. HFpEF was defined as EF ≥45%, and HFrEF was EF <45%. RESULTS: Among the 133 participants with incident ADHF who had EF assessment, 69 (52%) had HFpEF and 64 (48%) had HFrEF (P value: 0.73). During average 3.3 years follow-up in those who developed incident ADHF, rates of subsequent all-cause and HF hospital readmission and mortality were high, but there were no significant differences between those who developed HFpEF versus HFrEF. Randomization to the intensive arm had no effect on subsequent mortality or readmissions after the initial ADHF event, irrespective of EF subtype. During follow-up among participants who developed HFpEF, although relatively modest number of events limited statistical power, age was an independent predictor of all-cause mortality, and Black race independently predicted all-cause and HF hospital readmission. CONCLUSIONS: In SPRINT, intensive BP reduction decreased both acute decompensated HFpEF and HFrEF events. After initial incident ADHF, rates of subsequent hospital admission and mortality were high and were similar for those who developed HFpEF or HFrEF. Randomization to the intensive arm did not alter the risks for subsequent all-cause, or HF events in either HFpEF or HFrEF. Among those who developed HFpEF, age and Black race were independent predictors of clinical outcomes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.

SPRINT Revisited: Updated Results and Implications.

The SPRINT (Systolic Blood Pressure Intervention Trial) results have influenced clinical practice but have also generated discussion regarding the validity, generalizability, and importance of the findings. Following the SPRINT primary results manuscript in 2015, additional results and analyses of the data have addressed these concerns. The primary objective of this article is to respond to key questions that have been raised.

The Predialysis Serum Sodium Level Modifies the Effect of Hemodialysis Frequency on Left-Ventricular Mass: The Frequent Hemodialysis Network Trials.

INTRODUCTION: The Frequent Hemodialysis Network (FHN) Daily and Nocturnal trials aimed to compare the effects of hemodialysis (HD) given 6 versus 3 times per week. More frequent in-center HD significantly reduced left-ventricular mass (LVM), with more pronounced effects in patients with low urine volumes. In this study, we aimed to explore another potential effect modifier: the predialysis serum sodium (SNa) and related proxies of plasma tonicity. METHODS: Using data from the FHN Daily and Nocturnal Trials, we compared the effects of frequent HD on LVM among patients stratified by SNa, dialysate-to-predialysis serum-sodium gradient (GNa), systolic and diastolic blood pressure, time-integrated sodium-adjusted fluid load (TIFL), and extracellular fluid volume estimated by bioelectrical impedance analysis. RESULTS: In 197 enrolled subjects in the FHN Daily Trial, the treatment effect of frequent HD on ∆LVM was modified by SNa. When the FHN Daily Trial participants are divided into lower and higher predialysis SNa groups (less and greater than 138 mEq/L), the LVM reduction in the lower group was substantially higher (-28.0 [95% CI -40.5 to -15.4] g) than in the higher predialysis SNa group (-2.0 [95% CI -15.5 to 11.5] g). Accounting for GNa, TIFL also showed more pronounced effects among patients with higher GNa or higher TIFL. Results in the Nocturnal Trial were similar in direction and magnitude but did not reach statistical significance. DISCUSSION/CONCLUSION: In the FHN Daily Trial, the favorable effects of frequent HD on left-ventricular hypertrophy were more pronounced among patients with lower predialysis SNa and higher GNa and TIFL. Whether these metrics can be used to identify patients most likely to benefit from frequent HD or other dialytic or nondialytic interventions remains to be determined. Prospective, adequately powered studies studying the effect of GNa reduction on mortality and hospitalization are needed.

Text Messaging and Home Blood Pressure Monitoring for Patients with Uncontrolled Hypertension: Proposal for a Feasibility Pilot Randomized Controlled Trial.

BACKGROUND: A decrease in blood pressure, even modestly (ie, 2 mmHg), lowers cardiovascular morbidity and mortality. Low patient adherence to antihypertensive medication is the most significant modifiable patient-related barrier to achieving controlled blood pressure. Preliminary studies have shown that SMS text messaging and home blood pressure monitoring (HBPM) can be effective in promoting medication adherence and blood pressure control. The best strategy to engage with older patients of low socioeconomic status who are low adopters of technology and disproportionally affected by uncontrolled hypertension is still unknown. OBJECTIVE: The objective of this study is to improve blood pressure control in the older, low socioeconomic status population. The study will test two aims: First, we aim to evaluate the feasibility of conducting a randomized controlled trial by using an SMS-based approach among nonadherent, older patients of low socioeconomic status who have uncontrolled hypertension. Feasibility will be assessed in terms of recruitment rates per month (primary outcome); patient acceptability will be evaluated by monitoring retention rates and SMS response rates and using the validated Systems Usability Scale (secondary outcomes). Second, we aim to estimate the effects of the SMS approach on lowering blood pressure and adherence to antihypertensive medications. METHODS: We will recruit 24 patients of low socioeconomic status with uncontrolled hypertension (systolic BP>140 mmHg or diastolic BP>90 mmHg) showing low medication adherence and taking at least two antihypertensives, who have presented to two outpatient clinics of Wake Forest Baptist Health (Winston Salem, North Carolina, USA). Participants will be randomly assigned to either SMS and HBPM (n=12) or usual care and HBPM (n=12) intervention. Clinicians adjusting the patients' medications will be blinded to the study assignment. Text messages will be sent from a secure platform to assess medication adherence and HBPM on a weekly basis. The content and delivery frequency of the proposed SMS intervention are based on input from three focus groups conducted in Spring 2019. Participants in both study arms will receive education on HBPM and using an HBPM device. We hypothesize that we will successfully recruit 24 participants and the intervention will be acceptable to the participants. It will also improve medication adherence (assessed by question Medication Adherence Questionnaire scores) and blood pressure control. RESULTS: Our study was funded in July 2020. As of May 2021, we have enrolled 6 participants. CONCLUSIONS: Our findings will help design a larger efficacy trial to advance the field of eHealth delivery systems particularly for older adults of low socioeconomic status. This study addresses a highly significant topic and targets a population of high morbidity and mortality that has been traditionally underrepresented in clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT03596242; https://clinicaltrials.gov/ct2/show/NCT03596242. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/18984.

Final Report of a Trial of Intensive versus Standard Blood-Pressure Control.

BACKGROUND: In a previously reported randomized trial of standard and intensive systolic blood-pressure control, data on some outcome events had yet to be adjudicated and post-trial follow-up data had not yet been collected. METHODS: We randomly assigned 9361 participants who were at increased risk for cardiovascular disease but did not have diabetes or previous stroke to adhere to an intensive treatment target (systolic blood pressure, <120 mm Hg) or a standard treatment target (systolic blood pressure, <140 mm Hg). The primary outcome was a composite of myocardial infarction, other acute coronary syndromes, stroke, acute decompensated heart failure, or death from cardiovascular causes. Additional primary outcome events occurring through the end of the intervention period (August 20, 2015) were adjudicated after data lock for the primary analysis. We also analyzed post-trial observational follow-up data through July 29, 2016. RESULTS: At a median of 3.33 years of follow-up, the rate of the primary outcome and all-cause mortality during the trial were significantly lower in the intensive-treatment group than in the standard-treatment group (rate of the primary outcome, 1.77% per year vs. 2.40% per year; hazard ratio, 0.73; 95% confidence interval [CI], 0.63 to 0.86; all-cause mortality, 1.06% per year vs. 1.41% per year; hazard ratio, 0.75; 95% CI, 0.61 to 0.92). Serious adverse events of hypotension, electrolyte abnormalities, acute kidney injury or failure, and syncope were significantly more frequent in the intensive-treatment group. When trial and post-trial follow-up data were combined (3.88 years in total), similar patterns were found for treatment benefit and adverse events; however, rates of heart failure no longer differed between the groups. CONCLUSIONS: Among patients who were at increased cardiovascular risk, targeting a systolic blood pressure of less than 120 mm Hg resulted in lower rates of major adverse cardiovascular events and lower all-cause mortality than targeting a systolic blood pressure of less than 140 mm Hg, both during receipt of the randomly assigned therapy and after the trial. Rates of some adverse events were higher in the intensive-treatment group. (Funded by the National Institutes of Health; SPRINT ClinicalTrials.gov number, NCT01206062.).

Heart Failure Primary Prevention: What Does SPRINT Add?: Recent Advances in Hypertension.

Hypertension is the most prevalent modifiable factor for the development of heart failure. However, the optimal blood pressure (BP) target for preventing heart failure remains uncertain. The SPRINT (Systolic BP Intervention Trial) was a large, randomized open-label trial (n=9361 participants) that showed the superiority of a systolic BP target of <120 mm Hg compared with <140 mm Hg, with a 36% lower rate of acute decompensated heart failure (ADHF) events. This beneficial effect was consistent across all the key prespecified subgroups, including advanced age, chronic kidney disease, and prior cardiovascular disease. Participants who had an ADHF event had a markedly increased risk of subsequent cardiovascular disease events, including recurrent ADHF. Randomization to the intensive arm did not affect the recurrence of ADHF after the initial ADHF event (hazard ratio, 0.93 [95% CI, 0.50-1.67]; P=0.81). A separate analysis demonstrated that the reduction in ADHF events in the intensive treatment group in SPRINT was not due to the differential use of diuretics between the 2 treatment groups. Although intensive BP treatment resulted in a lower cardiovascular disease event rate, this was not significantly associated with changes in left ventricular mass, function, or fibrosis, as assessed in SPRINT HEART, an ancillary study to SPRINT. Intensive BP treatment, however, significantly attenuated increases in carotid-femoral pulse wave velocity. Overall, these data highlight the importance of preventing ADHF in high cardiovascular risk hypertensive patients by optimal BP reduction as tested in SPRINT.

Effect of Intensive Blood Pressure Control on Aortic Stiffness in the SPRINT-HEART.

[Figure: see text].