Intensive Systolic Blood Pressure Treatment Research Articles

Impact of Hypertension Duration on the Cardiovascular Benefit of Intensive Blood Pressure Control.

The optimal timing for initiating intensive systolic blood pressure (SBP) treatment remains unclear. While longer hypertension duration is positively associated with increased cardiovascular disease risk, it is unknown whether patients with prolonged hypertension can derive similar benefits from intensive SBP treatment. From the STEP trial (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients), 8442 participants with complete hypertension duration data were categorized by hypertension duration ≤5 years, 5 to 10 years, 10 to 15 years, and >15 years. The primary outcome was a composite of cardiovascular events. Hazard ratios were calculated using the Fine-Gray subdistribution hazard model. The incidences of the primary outcome increased significantly in patients with hypertension over 15 years than those <5 years in the standard SBP treatment group (adjusted hazard ratios, 1.68 [95% CI, 1.11-2.56]) but not in the intensive treatment group. Each 1-year increase in hypertension duration continuously increased the adjusted risk of major cardiovascular events by 4% (95% CI, 1.01-1.08) up to 20 years, plateauing at an adjusted hazard ratio of 2.27 (95% CI, 1.28-4.04). After intensive SBP treatment, the incidences of major cardiovascular events were similar across different hypertension duration groups, which were 2.22%, 1.69%, 3.02%, and 2.52%, respectively (P>0.05). Subgroup analyses indicated a potential sex difference in this relationship between hypertension duration and the primary outcome in the standard SBP treatment group (Pinteraction=0.05). Initiating intensive SBP treatment at any stage of hypertension duration could reduce cardiovascular disease risk to a comparable level. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03015311.

Estimated Population Health Benefits of Intensive Systolic Blood Pressure Treatment Among SPRINT-Eligible US Adults.

The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated an intensive (<120 mm Hg) vs. standard (<140 mm Hg) systolic blood pressure (SBP) goal lowered cardiovascular disease (CVD) risk. Estimating the effect of intensive SBP lowering among SPRINT-eligible adults most likely to benefit can guide implementation efforts. We studied SPRINT participants and SPRINT-eligible participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study and National Health and Nutrition Examination Surveys (NHANES). A published algorithm of predicted CVD benefit with intensive SBP treatment was used to categorize participants into low, medium, or high predicted benefit. CVD event rates were estimated with intensive and standard treatment. Median age was 67.0, 72.0, and 64.0 years in SPRINT, SPRINT-eligible REGARDS, and SPRINT-eligible NHANES participants, respectively. The proportion with high predicted benefit was 33.0% in SPRINT, 39.0% in SPRINT-eligible REGARDS, and 23.5% in SPRINT-eligible NHANES. The estimated difference in CVD event rate (standard minus intensive) was 7.0 (95% confidence interval [CI] 3.4-10.7), 8.4 (95% CI 8.2-8.5), and 6.1 (95% CI 5.9-6.3) per 1,000 person-years in SPRINT, SPRINT-eligible REGARDS participants, and SPRINT-eligible NHANES participants, respectively (median 3.2-year follow-up). Intensive SBP treatment could prevent 84,300 (95% CI 80,800-87,920) CVD events per year in 14.1 million SPRINT-eligible US adults; 29,400 and 28,600 would be in 7.0 million individuals with medium or high predicted benefit, respectively. Most of the population health benefit from intensive SBP goals could be achieved by treating those characterized by a previously published algorithm as having medium or high predicted benefit.

REMNANT CHOLESTEROL AND INTENSIVE BLOOD PRESSURE CONTROL IN OLDER PATIENTS WITH HYPERTENSION: A POST HOC ANALYSIS OF THE STEP RANDOMIZED TRIAL

Objective: Emerging evidence shows the close relationship between remnant cholesterol (RC) and hypertension. However, it is unknown whether RC is associated with the effect of intensive systolic blood pressure (SBP) lowering on cardiovascular outcomes. We aimed to determine the influence of baseline RC on the effect of intensive SBP lowering in hypertensive patients. Design and method: We performed a post-hoc analysis of the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Participants were randomly allocated to intensive SBP treatment (110 to &lt;130 mmHg) or standard SBP treatment (130 to &lt;150 mmHg). RC was calculated as total cholesterol minus high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol. The median RC concentration was used to categorize participants into low and high RC groups. The primary outcome was a composite of stroke, acute coronary syndrome, acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes. Results: Of the 8,511 participants in the STEP trial, 8,276 participants had available baseline RC concentrations (low RC group: n = 4,200; high RC group: n = 4,076). After a median follow-up of 3.33 years, a reduction in the primary outcome was observed in participants allocated to receive intensive SBP lowering in both groups; however, the reduction was only significant in the high RC group (high RC group: adjusted hazard ratio [aHR] 0.62; 95% confidence interval [CI] 0.45–0.84; low RC group: 0.91 [0.67–1.24]; P for interaction = 0.09). Intensive SBP treatment decreased all-cause mortality in the high RC group (aHR 0.48; 95% CI 0.28 – 0.81) but increased it in the low RC group (aHR 2.51; 95% CI 1.47 – 4.28; P for interaction &lt;0.001). Among the adverse events, only hypotension was slightly increased in the high RC group (adjusted relative risk 1.48; 95% CI 1.02 – 2.16). Conclusions: Patients with high RC experienced greater cardiovascular benefits with intensive SBP lowering.

Association of Intensive vs Standard Blood Pressure Control With Regional Changes in Cerebral Small Vessel Disease Biomarkers

Little is known about the associations of strict blood pressure (BP) control with microstructural changes in small vessel disease markers. To investigate the regional associations of intensive vs standard BP control with small vessel disease biomarkers, such as white matter lesions (WMLs), fractional anisotropy (FA), mean diffusivity (MD), and cerebral blood flow (CBF). The Systolic Blood Pressure Intervention Trial (SPRINT) is a multicenter randomized clinical trial that compared intensive systolic BP (SBP) control (SBP target <120 mm Hg) vs standard control (SBP target <140 mm Hg) among participants aged 50 years or older with hypertension and without diabetes or a history of stroke. The study began randomization on November 8, 2010, and stopped July 1, 2016, with a follow-up duration of approximately 4 years. A total of 670 and 458 participants completed brain magnetic resonance imaging at baseline and follow-up, respectively, and comprise the cohort for this post hoc analysis. Statistical analyses for this post hoc analysis were performed between August 2020 and October 2022. At baseline, 355 participants received intensive SBP treatment and 315 participants received standard SBP treatment. The main outcomes were regional changes in WMLs, FA, MD (in white matter regions of interest), and CBF (in gray matter regions of interest). At baseline, 355 participants (mean [SD] age, 67.7 [8.0] years; 200 men [56.3%]) received intensive BP treatment and 315 participants (mean [SD] age, 67.0 [8.4] years; 199 men [63.2%]) received standard BP treatment. Intensive treatment was associated with smaller mean increases in WML volume compared with standard treatment (644.5 mm3 vs 1258.1 mm3). The smaller mean increases were observed specifically in the deep white matter regions of the left anterior corona radiata (intensive treatment, 30.3 mm3 [95% CI, 16.0-44.5 mm3]; standard treatment, 80.5 mm3 [95% CI, 53.8-107.2 mm3]), left tapetum (intensive treatment, 11.8 mm3 [95% CI, 4.4-19.2 mm3]; standard treatment, 27.2 mm3 [95% CI, 19.4-35.0 mm3]), left superior fronto-occipital fasciculus (intensive treatment, 3.2 mm3 [95% CI, 0.7-5.8 mm3]; standard treatment, 9.4 mm3 [95% CI, 5.5-13.4 mm3]), left posterior corona radiata (intensive treatment, 26.0 mm3 [95% CI, 12.9-39.1 mm3]; standard treatment, 52.3 mm3 [95% CI, 34.8-69.8 mm3]), left splenium of the corpus callosum (intensive treatment, 45.4 mm3 [95% CI, 25.1-65.7 mm3]; standard treatment, 83.0 mm3 [95% CI, 58.7-107.2 mm3]), left posterior thalamic radiation (intensive treatment, 53.0 mm3 [95% CI, 29.8-76.2 mm3]; standard treatment, 106.9 mm3 [95% CI, 73.4-140.3 mm3]), and right posterior thalamic radiation (intensive treatment, 49.5 mm3 [95% CI, 24.3-74.7 mm3]; standard treatment, 102.6 mm3 [95% CI, 71.0-134.2 mm3]). This study suggests that intensive BP treatment, compared with standard treatment, was associated with a slower increase of WMLs, improved diffusion tensor imaging, and FA and CBF changes in several brain regions that represent vulnerable areas that may benefit from more strict BP control. ClinicalTrials.gov Identifier: NCT01206062.

Effects of intensive vs. standard blood pressure control on cognitive function: Post-hoc analysis of the STEP randomized controlled trial.

The STEP (Strategy of Blood Pressure Intervention in the older Hypertensive Patients) trial showed that intensive systolic blood pressure (SBP) control resulted in a lower incidence of cardiovascular events than standard treatment. This study analyzed the effects of intensive SBP lowering on cognitive function. STEP was a multicenter, randomized controlled trial of hypertensive patients aged 60-80 years. Participants were randomly assigned (1:1) to SBP goals of 110-130 mmHg (intensive treatment) or 130-150 mmHg (standard treatment). Each individual was asked to complete a cognitive function test (Mini-Mental State Examination; MMSE) at baseline and during follow-up. The primary outcome for this study was the annual change in MMSE score. Subjects with a score less than education-specific cutoff point were categorized as cognitive decline. The analysis enrolled 6,501 participants (3,270 participants in the intensive-treatment and 3,231 participants in the standard-treatment groups). Median follow-up was 3.34 years. There was a minor change in MMSE score, with an annual change of -0.001 [95% confidence interval [CI] -0.020, 0.018] and 0.030 (95% CI 0.011, 0.049) in the intensive- and standard-treatment groups, respectively (p = 0.052). Cognitive decline occurred in 46/3,270 patients (1.4%) in the intensive-treatment group and 42/3,231 (1.3%) in the standard-treatment group (hazard ratio 0.005, 95% CI 0.654, 1.543, p = 0.983). Compared with standard treatment, intensive SBP treatment did not result in a significant change in cognitive function test score. The impact of intensive blood pressure lowering was not evident using this global cognitive function test. ClinicalTrials.gov. Unique identifier: NCT03015311.

Intensive systolic blood pressure treatment remodels brain perivascular spaces: A secondary analysis of the Systolic Pressure Intervention Trial (SPRINT)

BackgroundBrain perivascular spaces (PVS) are part of the glymphatic system and facilitate clearance of metabolic byproducts. Since enlarged PVS are associated with vascular health, we tested whether intensive systolic blood pressure (SBP) treatment affects PVS structure. MethodsThis is a secondary analysis of the Systolic PRessure INtervention Trial (SPRINT) MRI Substudy: a randomized trial of intensive SBP treatment to goal < 120 mm Hg vs < 140 mm Hg. Participants had increased cardiovascular risk, pre-treatment SBP 130–180, and no clinical stroke, dementia, or diabetes. Brain MRIs acquired at baseline and follow-up were used to automatically segment PVS in the supratentorial white matter and basal ganglia using a Frangi filtering method. PVS volumes were quantified as a fraction of the total tissue volume. The effects of SBP treatment group and major antihypertensive classes on PVS volume fraction were separately tested using linear mixed-effects models while covarying for MRI site, age, sex, Black race, baseline SBP, history of cardiovascular disease (CVD), chronic kidney disease, and white matter hyperintensities (WMH). ResultsFor 610 participants with sufficient quality MRI at baseline (mean age 67 ± 8, 40 % female, 32 % Black), greater PVS volume fraction was associated with older age, male sex, non-Black race, concurrent CVD, WMH, and brain atrophy. For 381 participants with MRI at baseline and at follow-up (median ± IQR = 3.9 ± 0.4 years), intensive treatment was associated with decreased PVS volume fraction relative to standard treatment (interaction coefficient: −0.029 [−0.055 to −0.0029] p = 0.029). Reduced PVS volume fraction was also associated with exposure to calcium channel blockers (CCB). ConclusionsPVS enlargement was partially reversed in the intensive SBP treatment group. The association with CCB use suggests that improved vascular compliance may be partly responsible. Improved vascular health may facilitate glymphatic clearance.Clincaltrials.gov: NCT01206062.

Safety and efficacy of intensive systolic blood pressure lowering after successful endovascular therapy: a post hoc analysis of the BP TARGET trial

BackgroundThe Safety and Efficacy of Intensive Blood Pressure Lowering after Successful Endovascular Therapy in Acute Ischaemic Stroke (BP TARGET) trial demonstrated no benefit from intensive systolic blood pressure (SBP) treatment...

Abstract WMP87: Effect Of Intensive Blood Pressure Treatment After Successful Reperfusion On Outcome According To End Of Procedure Blood Pressure: Insight From The Bp Target Trial

Backgroup: The Safety and efficacy of intensive blood pressure lowering after successful endovascular therapy in acute ischaemic stroke (BP TARGET) trial demonstrated no benefit of systolic blood pressure (SBP) intensive lowering treatment after successful reperfusion. However, it is still unknown whether end of procedure SBP modifies the treatment effect of SBP intensive lowering treatment after successful reperfusion. Methods: This is a post hoc analysis of the BP TARGET multicenter trial. Patients were enrolled in the BP TARGET trial if they achieved successful reperfusion with EVT and had systolic blood pressure (SBP) ≥130 mmHg at the end of procedure. Patients were randomized in 1:1 fashion to intensive SBP treatment (SBP target 100-129 mmHg to be achieved within 1 hour of randomization) or standard SBP treatment (SBP target 130-185 mmHg). In this study, patients were divided into two groups based on end of procedure SBP (&lt;160 mmHg, ≥ 160 mmHg). Primary outcome was any intracerebral hemorrhage and secondary outcome was favorable outcome ( modified Rankin Scale 0-2 ) at 90 days. Results: A total of 290 patients were included in the present study (141 patients in the intensive treatment arm and 149 patients in the standard arm). A total of 105 patients had end of procedure SBP≥160 mmHg (53 in the intensive arm and 52 in the standard arm) and 185 patients had SBP&lt;160mmHg (88 in the intensive arm and 97 in the standard arm). Intensive SBP treatment was not associated with any intracerebral hemorrhage or favorable outcome in both &lt;160 mmHg and ≥160mmHg groups (Table 1). Moreover, there was no heterogeneity of treatment effect according to end of procedure SBP. Conclusion: End of procedure SBP did not modify the treatment effect of SBP lowering treatment after successful reperfusion.

Patient Selection for Intensive Blood Pressure Management Based on Benefit and Adverse Events

BackgroundIntensive systolic blood pressure (SBP) treatment prevents cardiovascular disease (CVD) events in patients with high CVD risk on average, though benefits likely vary among patients. ObjectivesThe aim of this study was to predict the magnitude of benefit (reduced CVD and all-cause mortality risk) along with adverse event (AE) risk from intensive versus standard SBP treatment. MethodsThis was a secondary analysis of SPRINT (Systolic Blood Pressure Intervention Trial). Separate benefit outcomes were the first occurrence of: 1) a CVD composite of acute myocardial infarction or other acute coronary syndrome, stroke, heart failure, or CVD death; and 2) all-cause mortality. Treatment-related AEs of interest included hypotension, syncope, bradycardia, electrolyte abnormalities, injurious falls, and acute kidney injury. Modified elastic net Cox regression was used to predict absolute risk for each outcome and absolute risk differences on the basis of 36 baseline variables available at the point of care with intensive versus standard treatment. ResultsAmong 8,828 SPRINT participants (mean age 67.9 years, 35% women), 600 CVD composite events, 363 all-cause deaths, and 481 treatment-related AEs occurred over a median follow-up period of 3.26 years. Individual participant risks were predicted for the CVD composite (C index = 0.71), all-cause mortality (C index = 0.75), and treatment-related AEs (C index = 0.69). Higher baseline CVD risk was associated with greater benefit (i.e., larger absolute CVD risk reduction). Predicted CVD benefit and predicted increased treatment-related AE risk were correlated (Spearman correlation coefficient = −0.72), and 95% of participants who fell into the highest tertile of predicted benefit also had high or moderate predicted increases in treatment-related AE risk. Few were predicted as high benefit with low AE risk (1.8%) or low benefit with high AE risk (1.5%). Similar results were obtained for all-cause mortality. ConclusionsSPRINT participants with higher baseline predicted CVD risk gained greater absolute benefit from intensive treatment. Participants with high predicted benefit were also most likely to experience treatment-related AEs, but AEs were generally mild and transient. Patients should be prioritized for intensive SBP treatment on the basis of higher predicted benefit. (Systolic Blood Pressure Intervention Trial [SPRINT]; NCT01206062)

Abstract P179: The Magnitude, And Not Direction, Of Blood Pressure Change Influences The Risk Of Serious Adverse Events In SPRINT

Background: The landmark Systolic Blood Pressure Intervention Trial (SPRINT) showed that more intensive systolic blood pressure treatment (SBP &lt; 120 mm Hg) was associated with lower risk for cardiovascular events and mortality but higher risk for serious adverse events (SAEs). However, it is unclear if the magnitude and/or the direction of the BP change determines SAE risk. In this study, we aim to determine how the magnitude and direction of BP change impacts SAE risk. Methods: This is a secondary analysis of 7922 participants in SPRINT. Time-varying Cox proportional hazards models were used to explore the relationship between visit-to-visit BP change and SAE risk. BP change was categorized using five intervals: 1) decreases ≥30 mm Hg, 2) decreases 10-29 mm Hg, 3) increases or decreases &lt;10 mm Hg (reference category), 4) increases 10-29 mm Hg, and 5) increases ≥30 mm Hg. Additional variables adjusted for in the model included: age, gender, race, estimated glomerular filtration rate, treatment group, and baseline atherosclerotic cardiovascular disease (ASCVD) risk. Hypotension was excluded as an SAE to prevent bias in SAE risk in the large BP decrease category. Results: The hazard ratio (HR) for SAEs compared to the minimal BP change category was greatest for BP increases above 30 mm Hg (HR = 1.62, 95% confidence interval [1.30, 2.01]). However, the HR was similar for sharp BP decreases over 30 mm Hg (HR = 1.52 [1.23, 1.87]). Milder BP increases and decreases were associated with lower SAE risk (HR = 1.18 [1.06, 1.32] and HR = 1.10 [0.98, 1.22] for BP changes 10 to 30 mm Hg and -30 to -10 mm Hg, respectively). There were no significant interactions between BP change, intensive treatment, and baseline ASCVD risk. Conclusions: SAE risk was similar for similarly sized increases and decreases in BP between visits, with higher magnitude changes associated with higher SAE risk. When accounting for the magnitude of BP change, no significant effect of intensive treatment or baseline ASCVD risk was found.

Abstract 103: The Effects of s Lower Blood Pressure Treatment Goal on Orthostatic Hypotension in Adults With Recent Stroke

Background: Lower systolic blood pressure (SBP) treatment goals reduce risk of orthostatic hypotension (OH). Whether a lower goal also reduces orthostatic symptoms is unknown. Methods: We examined the effect of SBP goal on OH in SPS3-BP (Secondary Prevention of Small Subcortical Strokes - Blood Pressure), an open label, randomized trial. Adults with a recent stroke (&lt;6 months) were assigned to either a SBP goal of 130-149 mm Hg or &lt;130 mm Hg. During follow-up, BP was measured 3 times in a seated position and once after 2 minutes of standing. OH was defined as a drop in SBP ≥20 mm Hg or DBP ≥10 mm Hg. We also examined extreme standing BP values (SBP ≥190 mm Hg or ≤90 mm Hg; DBP ≥110 mm Hg or ≤40 mm Hg). Participants were asked about dizziness and lightheadedness in the process of standing up. We used generalized estimating equations to account for repeat measurements. Results: During 36,342 visits, involving 2,876 participants (mean age 62.8 ± 10.7 yrs, 37% women, 16% black) with a mean of 15 follow-up visits, OH was present 2,591 times in 1,165 participants. Similarly, dizziness was present 1,343 times (in 592 participants) and lightheadedness was present 941 times (in 893 participants). A lower SBP goal (compared to standard) was associated with a lower risk of OH (OR 0.86; 95% CI: 0.75, 0.99), a higher risk of SBP ≤90 mm Hg (3.79; 2.35, 6.11) or DBP ≤40 mm Hg (2.42; 1.41, 4.15), and a lower risk of SBP ≥190 mm Hg (0.40; 0.27, 0.60) or DBP ≥110 mm Hg (0.31; 0.19, 0.50) ( Table ). BP goal did not affect dizziness or lightheadedness. Conclusions: A lower SBP goal decreased OH without affecting orthostatic symptoms. These findings support recent observations that more intensive SBP treatment does not increase risk of falls.

A1177 Effect of Intensive versus Standard Blood Pressure Treatment According to Baseline Systolic Blood Pressure

Objectives: To determine whether the effects of intensive (<120 mmHg) compared with standard (<140 mmHg) systolic blood pressure (SBP) treatment are different among those with different baseline SBP in SPRINT. Methods: De-identified SPRINT database was used for this post hoc analysis. SPRINT participants were categorized by baseline SBP status, defined as high-SBP (≥140 mmHg) group versus those with low-SBP (<140 mmHg) group. The primary outcome was a composite of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, or death from cardiovascular causes. Treatment-related adverse events including hypotension, syncope, injurious falls, electrolyte abnormalities, and bradycardia were also evaluated. Cox regression was used to calculate hazard ratios for study outcomes with intensive compared with standard SBP treatment between these two groups. Results: Among 9,361 participants randomized (age 67.9 ± 9.4 years; 35.5% female), 4,964 and 4,397 had baseline low-SBP (<140 mmHg) and high-SBP (≥140 mmHg), respectively. After a median follow-up of 3.26 years, the hazard ratio for the primary outcome was 0.65 (95% CI 0.50, 0.83) and 0.84 (95% CI 0.66, 1.06) among those with low-SBP group and high-SBP group, respectively (P value for interaction 0.15). For treatment-related adverse events, the hazard ratio with intensive SBP treatment was 2.03 (95% CI 1.44, 2.85) for low-SBP group and 1.80 (95% CI 1.32, 2.47) for high-SBP group (P value for interaction 0.28). Conclusion: In SPRINT, the beneficial effects of intensive SBP treatment might be taken away among those with high baseline SBP level.

Influence of baseline systolic blood pressure on the relationship between intensive blood pressure control and cardiovascular outcomes in the Systolic Blood Pressure Intervention Trial (SPRINT).

To determine whether the effects of intensive (< 120mmHg) compared with standard (< 140mmHg) systolic blood pressure (SBP) treatments are different among those with different baseline SBP. De-identified SPRINT database was used for this post hoc analysis. SPRINT participants were categorized by baseline SBP status, defined as high-SBP (≥ 140mmHg) group versus the low-SBP (< 140mmHg) group. The primary outcome was a composite of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, or death from cardiovascular causes. Treatment-related adverse events including hypotension, syncope, and bradycardia were also evaluated. Cox regression was used to calculate hazard ratios for study outcomes with intensive compared with standard SBP treatment between these two groups. Among 9361 participants randomized (age 67.9 ± 9.4years; 35.5% female), 4964 and 4397 had baseline low SBP (< 140mmHg) and high SBP (≥ 140mmHg), respectively. After a median follow-up of 3.26years, the hazard ratio for the primary outcome was 0.65 (95% CI 0.50, 0.83) and 0.84 (95% CI 0.66, 1.06) among those in the low-SBP group and high-SBP group, respectively (P value for interaction 0.15). For treatment-related adverse events, the hazard ratio with intensive SBP treatment was 2.03 (95% CI 1.44, 2.85) for the low-SBP group and 1.80 (95% CI 1.32, 2.47) for the high-SBP group (P value for interaction 0.28). Hypertensive patients with low baseline SBP may benefit from intensive SBP lowering, whereas benefits were inconclusive among those with high baseline SBP.

Effect of Intensive Versus Standard Blood Pressure Treatment According to Baseline Prediabetes Status: A Post Hoc Analysis of a Randomized Trial.

To determine whether the effects of intensive (<120 mmHg) compared with standard (<140 mmHg) systolic blood pressure (SBP) treatment are different among those with prediabetes versus those with fasting normoglycemia at baseline in the Systolic Blood Pressure Intervention Trial (SPRINT). This was a post hoc analysis of SPRINT. SPRINT participants were categorized by prediabetes status, defined as baseline fasting serum glucose ≥100 mg/dL versus those with normoglycemia (fasting serum glucose <100 mg/dL). The primary outcome was a composite of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, or death from cardiovascular causes. Cox regression was used to calculate hazard ratios for study outcomes with intensive compared with standard SBP treatment among those with prediabetes and normoglycemia. Among 9,361 participants randomized (age 67.9 ± 9.4 years; 35.5% female), 3,898 and 5,425 had baseline prediabetes and normoglycemia, respectively. After a median follow-up of 3.26 years, the hazard ratio for the primary outcome was 0.69 (95% CI 0.53, 0.89) and 0.83 (95% CI 0.66, 1.03) among those with prediabetes and normoglycemia, respectively (P value for interaction 0.30). For all-cause mortality, the hazard ratio with intensive SBP treatment was 0.77 (95% CI 0.55, 1.06) for prediabetes and 0.71 (95% CI 0.54, 0.94) for normoglycemia (P value for interaction 0.74). Effects of intensive versus standard SBP treatment on prespecified renal outcomes and serious adverse events were similar for prediabetes and normoglycemia (all interaction P > 0.05). In SPRINT, the beneficial effects of intensive SBP treatment were similar among those with prediabetes and fasting normoglycemia.

Potential Deaths Averted and Serious Adverse Events Incurred From Adoption of the SPRINT (Systolic Blood Pressure Intervention Trial) Intensive Blood Pressure Regimen in the United States: Projections From NHANES (National Health and Nutrition Examination Survey).

SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated a 27% reduction in all-cause mortality with a systolic blood pressure (SBP) goal of <120 versus <140 mm Hg among US adults at high cardiovascular disease risk but without diabetes mellitus, stroke, or heart failure. To quantify the potential benefits and risks of SPRINT intensive goal implementation, we estimated the deaths prevented and excess serious adverse events incurred if the SPRINT intensive SBP treatment goal were implemented in all eligible US adults. SPRINT eligibility criteria were applied to the 1999 to 2006 National Health and Nutrition Examination Survey and linked with the National Death Index through December 2011. SPRINT eligibility included age ≥50 years, SBP of 130 to 180 mm Hg (depending on the number of antihypertensive medications being taken), and high cardiovascular disease risk. Exclusion criteria were diabetes mellitus, history of stroke, >1 g proteinuria, heart failure, estimated glomerular filtration rate <20 mL·min-1·1.73 m-2, or dialysis. Annual mortality rates were calculated by dividing the Kaplan-Meier 5-year mortality by 5. Hazard ratios for all-cause mortality and heart failure and absolute risks for serious adverse events in SPRINT were used to estimate the number of potential deaths and heart failure cases prevented and serious adverse events incurred with intensive SBP treatment. The mean age was 68.6 years, and 83.2% and 7.4% were non-Hispanic white and non-Hispanic black, respectively. The annual mortality rate was 2.20% (95% confidence interval [CI], 1.91-2.48), and intensive SBP treatment was projected to prevent ≈107 500 deaths per year (95% CI, 93 300-121 200) and give rise to 56 100 (95% CI, 50 800-61 400) episodes of hypotension, 34 400 (95% CI, 31 200-37 600) episodes of syncope, 43 400 (95% CI, 39 400-47 500) serious electrolyte disorders, and 88 700 (95% CI, 80 400-97 000) cases of acute kidney injury per year. The analysis-of-extremes approach indicated that the range of estimated lower- and upper-bound number of deaths prevented per year with intensive SBP control was 34 600 to 179 600. Intensive SBP control was projected to prevent 46 100 (95% CI, 41 800-50 400) cases of heart failure annually. If fully implemented in eligible US adults, intensive SBP treatment could prevent ≈107 500 deaths per year. A consequence of this treatment strategy, however, could be an increase in serious adverse events.

Abstract P178: Cost-Effectiveness of Intensive versus Standard Blood Pressure Goals by Baseline Systolic Blood Pressure Levels in SPRINT-Eligible US Adults

Background: In high-risk adults, intensive systolic blood pressure (SBP) goals (&lt;120 mmHg) reduced cardiovascular disease (CVD) events and mortality, when compared to standard SBP goals (&lt;140 mmHg), in the Systolic Blood Pressure Intervention Trial (SPRINT). While average benefit of reduced CVD risk with intensive SBP goals outweighs the average risk of serious adverse events (SAEs) and treatment costs, net intensive SBP goal benefits may vary by baseline SBP. We hypothesized that intensive SBP goals would be cost-effective vs. standard SBP goals when stratified by baseline SBP level in SPRINT-eligible US adults from the payer’s perspective. Methods: Using CVD event, death, and SAE risks, a microsimulation model compared direct healthcare costs and quality-adjusted life-years (QALYs) in the SPRINT intensive and standard SBP goal arms over patients’ remaining lifetimes. Published literature and national estimates were used for model parameters. The model assumed that, after the planned duration of SPRINT, adherence to treatment goals decayed over time. To estimate the effect of baseline SBP on the cost-effectiveness of intensive SBP goals, baseline SBP was stratified into the following groups: 130-139 mmHg, 140-149 mmHg, 150-159 mmHg, 160-169 mmHg, and 170-180 mmHg. Results: With higher baseline SBP, patients in both arms experienced higher rates of CVD events or CVD deaths and accrued higher costs compared with patients starting with lower baseline SBP. However, with higher baseline SBP, there were slightly more incremental QALYs gained with intensive SBP treatment, from 0.29 to 0.31. This led to a modestly better incremental cost-effectiveness ratio (ICER) for intensive vs. standard SBP goals, decreasing from approximately $50,000 to $43,000 per QALY gained as baseline SBP increased. If SPRINT treatment effects and in-trial adherence persisted for the remaining lifetime, the ICER for intensive SBP goals decreased to approximately $25,000-$26,000 per QALY gained across baseline SBP groups. Conclusions: Treatment of all SPRINT-eligible patients led to lifetime cost-effectiveness below accepted willingness-to-pay thresholds and lifetime net benefit and cost-effectiveness varied only modestly by baseline SBP. However, this analysis was based on summary data and did not account for individual patient risks. Multiple predictors, in addition to baseline SBP, may be needed to identify which SPRINT-eligible patients derive maximal benefit from intensive SBP treatment.

Abstract P180: Impact of Intensive Systolic Blood Pressure Treatment on Cardiovascular Disease and Mortality in the US Population

Introduction: Hypertension is the most important risk factor for cardiovascular disease (CVD), the leading cause of morbidity and mortality among US adults. Clinical trials suggest that intensive systolic blood pressure (BP) management significantly reduces risk of CVD and mortality in patients at high risk for CVD. However, the impact of intensive BP lowering in the US population is uncertain. Hypothesis: More intensive treatment of systolic BP provides great benefits in the reduction of CVD and total deaths in the US population aged ≥40 years. Methods: We pooled follow-up data in 31,851 individuals from four US cohort studies (ARIC, CHS, Framingham Heart Study, and MESA) to estimate annual incidence rates of major CVD (combined stroke, coronary heart disease, and heart failure) by sex, race (white and non-white), and age groups (40-49, 50-59, 60-69, and ≥70 years). We retrieved mortality data from annual death statistics reported by the CDC. We combined nationally-representative survey data from three NHANES cycles (2009-2010, 2011-2012, 2013-2014) to estimate the proportions of US adults aged ≥40 years in each of 10 systolic BP categories (range &lt;120 to ≥160 mm Hg). A Bayesian network meta-analysis of antihypertensive clinical trials was used to estimate relative risks for CVD and mortality comparing each of the 10 systolic BP categories, after adjusting for baseline risk in included trials. Using these data sources, we calculated the population attributable fractions and number of events (and deaths) that could be reduced by treating systolic BP ≥140 mmHg to more intensive systolic BP targets in the US population. Results: Treating systolic BP to 120-124 mm Hg showed the largest reduction in number of CVD events and total deaths compared to higher targets (Table). Conclusions: In conclusion, intensive treatment of systolic BP could prevent a large number of CVD events and total deaths in the US population.

Abstract P176: Impact of Serious Adverse Event Risks on the Cost-effectiveness of Intensive Blood Pressure Goals in Patients Aged ≥75 Years

Background: Compared to the overall Systolic Blood Pressure Intervention Trial (SPRINT) results, patients aged ≥75 years at baseline had a greater reduction in cardiovascular disease (CVD) events and all-cause mortality with an intensive systolic blood pressure (SBP) goal (&lt;120 mmHg) compared to a standard SBP goal (&lt;140 mmHg). Applying an intensive SBP goal in high-risk older patients represents a major shift in clinical practice and may increase concern for medication-related severe adverse events (SAEs). We hypothesized that the benefits of reduced CVD risk would outweigh the increased costs and SAE risk of intensive vs. standard SBP goals in SPRINT-eligible patients aged ≥75 years even when considering variable SAE risks. Methods: A microsimulation health-state transition model of 10,000 patients was created to estimate the CVD events, SAEs, quality-adjusted life years (QALYs), and direct healthcare costs of intensive vs. standard SBP goals. The model assumed patients were adherent to treatment during the median SPRINT follow-up, but that all patients would become non-adherent over 5 years. While adherent, CVD and SAE risks were derived from published SPRINT effect estimates for the ≥75 subgroup. Due to uncertainty in the SAE risk associated with intensive SBP goals in older adults, the intensive arm SAE risk was varied to determine the point at which treatment costs and harms outweighed CVD benefits at accepted willingness-to-pay thresholds. Healthcare costs and health state utilities were derived from national sources and other published estimates. Results: If SAE risk was equal to the observed rates in SPRINT, mean lifetime costs and QALYs were $268,000 and 7.85 for the intensive arm, and $262,000 and 7.60 for the standard arm. The resulting incremental cost-effectiveness ratio (ICER) was about $26,000 per QALY gained. However, as SAE risk in the intensive arm increased by 1.5, 2, and 2.5 times, the ICER increased to $33,000, $43,000, and $55,000 per QALY gained, respectively. Conclusion: Intensive SBP goals may be a cost-effective way to reduce CVD events and improve survival in patients aged ≥75 years, but safety and cost-effectiveness depend on medication-related SAE risk. However, these results are based on summary data and do not account for clustering of risks at the individual patient level. Thus, more precise prediction of risks and benefits is needed to guide selection of older patients for intensive SBP treatment goals.