Standard Blood Pressure Control Research Articles

A data-zone scoring system to assess the generalizability of clinical trial results to individual patients.

Evaluating the applicability of a clinical trial to a specific patient is difficult. A novel framework, the Trial Score, was created to quantify the generalizability of a trial's result based on participants' baseline characteristics and not on the trial's inclusion and exclusion criteria. For each Systolic Blood Pressure Intervention Trial (SPRINT) participant, the Euclidean distance in six-dimensional space from the theoretical "average" participant was calculated to produce an individual Trial Score that incorporates multiple distinct continuous-variable baseline characteristics. We prospectively defined the "data-rich," "data-limited," and "data-free" zones as Trial Scores < 90th percentile, the 90th-97.5th percentile, and >97.5th percentile, respectively. Trial Scores were then calculated for National Health and Nutrition Examination Survey participants to map data zones of the general population. Individual participant data from the Action to Control Cardiovascular Risk in Diabetes blood pressure trial (ACCORD-BP) was used to test if participants further from the average SPRINT participant behave differently than the overall SPRINT results. The National Health and Nutrition Examination Survey cohort and the ACCORD-BP trial demonstrate large percentages of participants in SPRINT's data-free and data-limited zones. Time-to-event rates seen with intensive and standard blood pressure control in SPRINT were the same as ACCORD-BP participants within SPRINT's data-rich zone (hazard ratio 0.97, p = 0.84 and hazard ratio 0.95, p = 0.70). However, these rates were significantly different than those of ACCORD-BP participants outside SPRINT's data-rich zone (hazard ratio 0.64, p < 0.01 and hazard ratio 0.77, p < 0.01). ACCORD-BP participants with SPRINT Trial Scores in the 90th percentile or below have similar event rates to SPRINT participants in both the intensive and standard blood pressure groups. Quantifying the difference between an individual patient and the average clinical trial participant holds promise as a tool to more precisely determine applicability of a specific trial to individual patients.

A Randomised Trial of Intensive versus Standard Blood-Pressure Control in Patients with a History of Stroke: The RESPECT Study

A Randomised Trial of Intensive versus Standard Blood-Pressure Control in Patients with a History of Stroke: The RESPECT Study

Abstract P121: The Effect of Intensive Blood Pressure Targets on Mortality in Chronic Kidney Disease Patients: An Individual Patient Data Meta-Analysis of Randomized Controlled Trials

Introduction: Current evidence is conflicting on whether intensive blood pressure (BP) management, specifically with targets of &lt;130/90 mmHg, produces a mortality benefit in non-diabetic chronic kidney disease (CKD) patients. MDRD, AASK, and SPRINT are the largest randomized controlled trials available investigating intensive targets in CKD patients. The MDRD and AASK recruited exclusively CKD patients, while SPRINT had a large CKD subpopulation within its cohort. MDRD assigned patients to a standard mean arterial pressure (MAP) target of 107 mmHg vs. an intensive target of 92 mmHg (achieved BPs of 134/81 mmHg vs 126/77 mmHg, respectively). AASK assigned African American patients to a MAP of 102-107 mmHg vs. &lt;92 mmHg (achieved BPs of 141/85 mmHg vs. 128/78 mmHg, respectively). SPRINT compared a systolic target of 140 mmHg vs. 120 mmHg (achieved BPs of 137/74 vs. 123/67 in the CKD subpopulation). Our study pools individual patient data (IPD) from these three trials. Methods: IPD for all patients in MDRD, AASK, and SPRINT were obtained and screened for non-diabetic CKD patients. The resulting 4537 patients were assigned to their original randomized intervention group – 2258 patients to the standard group and 2279 to the intensive group. The primary outcome was mortality. Statistical analysis for primary outcome was performed with Cox proportional hazards models stratified by clinical site/center. Interactions between outcome and trial enrollment were also assessed. Results: There was no statistically significant difference in mortality rate between intensive and standard BP control (HR: 0.84; 95% CI: 0.66, 1.07; p = 0.148). 126 patients (5.5%) in the intensive group and 149 patients (6.6%) in the standard group expired. No interaction was present between treatment and trial enrollment (MDRD, AASK, SPRINT) (p-value of interaction: 0.080). Conclusion: Intensive BP targets do not improve mortality for non-diabetic patients with CKD. Further investigation needs to be performed to determine if this lack of benefit is consistent across subpopulations.

Comparison of Frequency of Atherosclerotic Cardiovascular and Safety Events With Systolic Blood Pressure

Whether the benefit of intensive blood pressure (BP) control reduces atherosclerotic cardiovascular disease (ASCVD) risk without increasing risks of serious adverse events (SAEs) is unknown. We sought to assess differences in incident ASCVD and SAE with intensive BP control across the spectrum of 10-year ASCVD risk in the Systolic Blood Pressure Intervention Trial (SPRINT). SPRINT randomized 9,361 participants who were ≥50years old and ≥1 CVD risk factor to standard or intensive BP control (<120 or 130 to 139mm Hg). We excluded adults with clinical ASCVD or age ≥80. We included 6,875 participants. We compared hazard ratios (HR) and risk differences (RD) of incident ASCVD events or SAEs in all and across quartiles of baseline risk. Median predicted ASCVD risk was 15.9%. Intensive BP control significantly reduced ASCVD events (HR 0.75, 95% confidence interval 0.58, 0.97, p = 0.03; RD -0.94; -1.8, -0.1; p = 0.03). There was no difference in effect across quartiles of ASCVD risk. There was a non-significant increase in SAE with intensive BP control (HR 1.08, 1.00, 1.17 p = 0.06; RD 2.1, -0.1, 4.4, p = 0.03), and no difference in this effect across quartiles of risk. In SPRINT participants without baseline clinical ASCVD, the benefit of intensive BP control for primary prevention of ASCVD may extend to lower risk participants without an increase in SAE. In conclusion, lower risk adults with stage 1 hypertension meeting SPRINT eligibility may benefit from initiation of antihypertensives.

Sex Differences of Patients With Systemic Hypertension (From the Analysis of the Systolic Blood Pressure Intervention Trial [SPRINT

There are differences in the incidence, pathophysiology, and long-term effects of hypertension between women and men. We assessed sex-specific benefit-risk tradeoffs of different blood pressure (BP) goals in patients enrolled in the Systolic Blood Pressure Intervention Trial (SPRINT) after propensity score matching those with standard therapy (systolic BP <140mm Hg) to those with intensive therapy (systolic BP <120mm Hg; n = 9,106). Cox regression was conducted to compare standard versus intensive therapy in women and men with the composite outcome of myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. Women were generally healthier at baseline and had a lower cardiovascular risk. Men on intensive therapy had a lower risk of the composite outcome compared to those on standard therapy (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.57 to 0.86, p = 0.001) while in women no differences between therapy groups were observed (HR 0.82 [0.60 to 1.12], p = 0.206). For safety outcomes, women and men had increased risk of related serious adverse events with intensive treatment (HR 1.52 [1.06 to 2.18], p = 0.023 and HR 2.07 [1.55 to2.77], p < 0.001, respectively). In conclusion, our study demonstrated that women did not benefit from intensive compared to standard BP control. A potential explanation for this may be the lower baseline cardiovascular risk in women.

Effect of intensive versus standard blood pressure control on major adverse cardiac events and serious adverse events: A bivariate analysis of randomized controlled trials

ABSTRACTBackground: Intensive blood pressure (BP) lowering may offer protective effects against major adverse cardiac event (MACE) but is also associated with a greater risk of a serious adverse event (SAE). The risk-benefit profile of intensive versus standard BP control has not been comprehensively assessed. Methods: Four studies were identified from a systematic literature search for randomized controlled trials comparing intensive versus standard BP lowering that reported both MACE and SAE endpoints. A previously described statistical approach was applied to characterize the efficacy-safety tradeoff of BP control. The bivariate outcome was computed to quantitatively assess the net clinical benefit (NCB) of intensive BP lowering as compared to standard treatment, with positive values indicating increased risks and negative values indicating decreased risks. Results: Data from the SPRINT trial demonstrated that intensive strategy was superior in MACE but inferior in SAE, thereby eroding the NCB (bivariate outcome: 0.33% [−0.50% to 1.21%]). Intensive strategy from the SPS3 trial fulfilled non-inferiority in both MACE and SAE but did not reach a favorable NCB (−1.31% [−2.25% to 0.01%]). The ACCORD trial suggested that intensive strategy was non-inferior in MACE but inferior in SAE (−0.19% [−0.79% to 1.37%]). Results from the VALISH trial were inconclusive for SAE but suggested non-inferiority in MACE (−1.19% [−3.24% to 0.68%]). Conclusions: Compared to the standard blood pressure target, pooled data from randomized controlled trials suggest that intensive strategy did not achieve a net clinical benefit when weighing the benefit of MACE reduction against the risk of SAE under the bivariate framework.Abbreviations: Blood pressure (BP), diastolic blood pressure (DBP), major adverse cardiac event (MACE), net clinical benefit (NCB), serious adverse event (SAE), systolic blood pressure (SBP).

Effect of Standard vs Intensive Blood Pressure Control on Cerebral Blood Flow in Small Vessel Disease

Blood pressure (BP) lowering is considered neuroprotective in patients with cerebral small vessel disease; however, more intensive regimens may increase cerebral hypoperfusion. This study examined the effect of standard vs intensive BP treatment on cerebral perfusion in patients with severe small vessel disease. To investigate whether standard vs intensive BP lowering over 3 months causes decreased cerebral perfusion in small vessel disease. This randomized clinical trial took place at 2 English university medical centers. Patients were randomized via a central online system (in a 1:1 ratio). Seventy patients with hypertension and with magnetic resonance imaging-confirmed symptomatic lacunar infarct and confluent white matter hyperintensities were recruited between February 29, 2012, and October 21, 2015, and randomized (36 in the standard group and 34 in the intensive group). Analyzable data were available in 62 patients, 33 in the standard group and 29 in the intensive group, for intent-to-treat analysis. This experiment examines the 3-month follow-up period. Patients were randomized to standard (systolic, 130-140 mm Hg) or intensive (systolic, <125 mm Hg) BP targets, to be achieved through medication changes. Cerebral perfusion was measured using arterial spin labeling; the primary end point was change in global perfusion between baseline and 3 months, compared between treatment groups by analysis of variance. Linear regression compared change in perfusion against change in BP. Magnetic resonance imaging scan analysis was masked to treatment group. Among 62 analyzable patients, the mean age was 69.3 years, and 60% (n = 37) were male. The mean (SD) systolic BP decreased by 8 (12) mm Hg in the standard group and by 27 (17) mm Hg in the intensive group (P < .001), with mean (SD) achieved pressures of 141 (13) and 126 (10) mm Hg, respectively. Change in global perfusion did not differ between treatment groups: the mean (SD) change was -0.5 (9.4) mL/min/100 g in the standard group vs 0.7 (8.6) mL/min/100 g in the intensive group (partial η2, 0.004; 95% CI, -3.551 to 5.818; P = .63). No differences were observed when the analysis examined gray or white matter only or was confined to those achieving target BP. The number of adverse events did not differ between treatment groups, with a mean (SD) of 0.21 (0.65) for the standard group and 0.32 (0.75) for the intensive group (P = .44). Intensive BP lowering did not reduce cerebral perfusion in severe small vessel disease. isrctn.org Identifier: ISRCTN37694103.

Effect of intensive blood pressure control in patients with type 2 diabetes mellitus over 9 years of follow-up: A subgroup analysis of high-risk ACCORDION trial participants.

Although guidelines recommend strict blood pressure (BP) control in patients with type 2 diabetes mellitus (T2DM) and elevated cardiovascular risk, the long-term effects of this approach are unknown. We investigated the effect of intensive BP control on clinical outcomes in patients with T2DM over 9 years of follow-up. We included Action to Control Cardiovascular Risk in Diabetes - Blood Pressure participants in the standard glucose control arm who had established cardiovascular disease, chronic kidney disease, were ≥75 years of age or who had a 10-year coronary heart risk ≥15%. Participants were randomized to either intensive (systolic BP < 120 mm Hg) or standard (systolic BP < 140 mm Hg) BP control for an average of 5 years. Observational follow-up occurred for an average of 4 years thereafter. After an average total follow-up of 9 years, intensive BP control reduced the composite of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke by 25% (hazard ratio, 0.75; 95% confidence interval, 0.60-0.95; P = .02). The overall benefit was driven by a reduction in nonfatal myocardial infarction (P = .01). In this post-hoc analysis, the benefits of a fixed-duration intensive BP control intervention in patients with T2DM persisted throughout 9 years of follow-up.

Abstract P497: Re-analysis of the Systolic Blood Pressure Intervention Trial (SPRINT): The Renal Consequences of Intensive versus Standard Blood Pressure Lowering

Background: BP management guidelines suggest that persons with CKD should be treated to a SBP ≤ 140 mmHg. SPRINT compared this target to intensive SBP lowering (≤ 120 mmHg) in persons with and without CKD and found a reduced rate of CV events and all-cause mortality (ACM). However intensive therapy was associated with an increased risk of AKI. We extrapolated the results of SPRINT over a lifetime horizon to determine whether in the long-term, the benefit in terms of the primary outcome would be less economically attractive when the risks of more frequent AKI and subsequent CKD progression were considered. Methods: We re-configured the CKD Simulator, a Markov model of CKD progression, AKI events, fatal and non-fatal CV events, and ESRD. We recalibrated the model to be representative of the SPRINT cohort and compared intensive vs. standard blood pressure control among 10 million simulated persons with and without CKD over their lifetimes. Marginal treatment costs were calculated and hazard ratios for AKI, CV events and ACM observed in SPRINT were applied to the monthly probabilities of these events in the intensive SBP arm. Results: Lifetime average, discounted, costs per person associated with intensive vs. standard SBP lowering were predicted to be $35,811 and $30,584, respectively. Quality-adjusted, discounted average lifespans were 196.05 and 190.47 months, respectively. The cost of each quality-adjusted life-year gained by adopting intensive over standard BP lowering would be $11,220, significantly below the accepted cost-effectiveness threshold of $50,000. Intensive SBP control would reduce the lifetime incidence of at least one CV event by 5.5%, but increase the incidence of at least one AKI episode and ESRD by 1.7% and 0.7%, respectively. These differences were associated with average lifetime cost savings per person of $459 for CV events, but losses of $161 and $2,889 for AKI and ESRD. Discussion: Intensive SBP management would be cost-effective and associated with a significant lifetime reduction in CV events. However, there would be an increase in the lifetime risk of AKI and ESRD, contributing to 58% of the total increase in cost of intensive relative to usual SBP control. Intensive SBP lowering should be adopted judiciously in persons at high risk of ESRD.

Cost-Effectiveness of Intensive versus Standard Blood-Pressure Control

BackgroundIn the Systolic Blood Pressure Intervention Trial (SPRINT), adults at high risk for cardiovascular disease who received intensive systolic blood-pressure control (target, <120 mm Hg) had significantly lower rates of death and cardiovascular disease events than did those who received standard control (target, <140 mm Hg). On the basis of these data, we wanted to determine the lifetime health benefits and health care costs associated with intensive control versus standard control.MethodsWe used a microsimulation model to apply SPRINT treatment effects and health care costs from national sources to a hypothetical cohort of SPRINT-eligible adults. The model projected lifetime costs of treatment and monitoring in patients with hypertension, cardiovascular disease events and subsequent treatment costs, treatment-related risks of serious adverse events and subsequent costs, and quality-adjusted life-years (QALYs) for intensive control versus standard control of systolic blood pressure.ResultsWe determined that the mean number of QALYs would 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 to 79% below the willingness-to-pay threshold of $50,000 per QALY and 76 to 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.ConclusionsIn this simulation study, intensive systolic blood-pressure control prevented cardiovascular disease events and prolonged life and did so at levels below common willingness-to-pay thresholds per QALY, regardless of whether benefits were reduced after 5 years or persisted for the patient’s remaining lifetime. (Funded by the National Heart, Lung, and Blood Institute and others; SPRINT ClinicalTrials.gov number, NCT01206062.)

The optimal cut-off of blood pressure related to left ventricular diastolic dysfunction and remodeling in Asian diabetic patients

BackgroundAlthough a recent randomized trial found no difference between intensive and standard blood pressure (BP) control in patients with diabetes mellitus (DM), the debate over the optimal BP target continues. Thus, the present study investigated the effect of BP on the subclinical left ventricular (LV) function and structural changes in diabetic patients. MethodA total of 2649 patients with DM who received echocardiography were enrolled in this study. Study population was stratified by three groups according to BP and presence of hypertension (normal, <130/80mmHg; prehypertension, ≥130/80mmHg without hypertension; hypertension, ≥140/90mmHg or history of hypertension). The odds ratios (ORs) of impaired LV diastolic function and LV remodeling were analyzed using multivariate logistic regression analysis. The adjusted mean values of echocardiographic parameters related to LV diastolic function and remodeling were also evaluated. ResultWhen normal group was set as reference, the adjusted ORs [95% confidential interval (CI)] for impaired LV diastolic function was 2.45 (95% CI 1.84–3.24) in prehypertension, 3.51 (95% CI 2.57–4.80) in hypertension group. Adjusted ORs for LV remodeling only showed significant result in hypertension group [1.82 (95% CI 1.23–2.69)]. The adjusted mean value of LV diastolic function and structure also demonstrated LV deterioration in prehypertension and hypertension groups. ConclusionOur study showed the adverse influence of prehypertension and hypertension on subclinical LV deterioration. This finding suggested the potential clinical benefits of intensive BP control (<130/80mmHg) in patients with DM.

4118A meta-analysis on standard and intensive blood pressure control in patients with chronic kidney disease

4118A meta-analysis on standard and intensive blood pressure control in patients with chronic kidney disease

Abstract 502: Effect of Intensive Versus Standard Blood Pressure Control on Stroke and Serious Adverse Event: A Bivariate Analysis on the Net Clinical Benefit

Background: Intensive blood pressure (BP) control is associated with a reduced risk of stroke but a greater risk of serious adverse event (SAE), thereby offsetting the benefit-to-risk ratio of this strategy. Methods: Using a previously described method of bivariate analysis, efficacy and safety outcomes were collectively analyzed as net clinical benefit (NCB) based on data from three randomized controlled trials comparing intensive versus standard BP control among 17,115 patients (ACCORD, SPS3, and SPRINT trials). Bivariate risk difference was assessed by the minimum distance from NCB curve to 95% CI of risk difference in all-cause stroke and SAE. Results: Compared to standard BP target, intensive strategies reduced all-cause stroke by 0.70% (95% CI: 0.19% to 1.21%; P = 0.007) and increased SAE by 1.85% (95% CI: 1.35% to 2.34%; P &lt; 0.0001). With a non-inferiority margin of 25%, standard strategy was preferable with respect to NCB in diabetics (bivariate risk difference: 1.29% [0.40% to 2.31%]) and in patients without diabetes or prior stroke (1.55% [0.76% to 2.37%]). Among patients with stroke history, intensive strategy failed to achieve non-inferiority in NCB (-0.18% [-1.01% to 0.83%]). Conclusions: Bivariate analysis is a novel method that allows simultaneous display and assessment of efficacy and safety outcomes. Among patients with cardiovascular risk factors, intensive BP control failed to demonstrate a favorable risk-benefit profile against standard BP control with respect to the tradeoff between stroke and SAE. Figure 1. Net clinical benefit of intensive vs standard BP control Figure 2. Forest plot of bivariate risk difference in stroke and SAE

Personalizing the Intensity of Blood Pressure Control: Modeling the Heterogeneity of Risks and Benefits From SPRINT (Systolic Blood Pressure Intervention Trial).

In SPRINT (Systolic Blood Pressure Intervention Trial), patients with hypertension and high cardiovascular risk treated with intensive blood pressure (BP) control (<120 mm Hg) had fewer major adverse cardiovascular events (MACE) and deaths but higher rates of treatment-related serious adverse events (SAE) than patients randomized to standard BP control (<140 mm Hg). However, the degree of benefit or harm for an individual patient could vary because of heterogeneity in treatment effect. Using patient-level data from 9361 randomized patients in SPRINT, we developed models to predict risk for MACE or death and treatment-related SAE to allow for individualized BP treatment goals based on each patient's projected risk and benefit of intensive versus standard BP control. Models were internally validated using bootstrap resampling and externally validated on 4741 patients from the ACCORD-BP (The Action to Control Cardiovascular Risk in Diabetes blood pressure) trial. Among 9361 SPRINT patients, 755 patients (8.1%) had a MACE or death event and 338 patients (3.6%) had a treatment-related SAE during a median follow-up of 3.3 years. The MACE/death and the SAE model had C statistics of 0.72 and 0.70, respectively, in the derivation cohort and 0.69 and 0.65 in ACCORD. The MACE/death model had 10 variables including treatment interactions with age, baseline systolic BP, and diastolic BP, and the SAE model had 8 variables including treatment interaction with number of BP medications. Intensive BP treatment was associated with a mean 2.2±2.6% lower risk of MACE/death compared with standard treatment (range, 20.7% lower risk to 19.6% greater risk among individual patients) and a mean 2.2±1.2% higher risk for SAEs (range, 0.5%-15.8% more harm in individual patients). To translate the findings from SPRINT to clinical practice, we developed prediction models to tailor the intensity of BP control based on the projected risk and benefit for each unique patient. This approach should be prospectively tested to better engage patients in shared medical decision making and to improve outcomes. URL: https://clinicaltrials.gov. Unique identifier: NCT01206062.

Hypertension: Controversies in blood-pressure goals among the elderly.

The optimal blood-pressure (BP) goals for elderly patients remain inconclusive, despite the recent publication of meta-analyses comparing intensive BP control with standard BP control. In searching for therapeutic approaches in these patients, researchers should change the focus from optimal BP values to a more holistic, individual approach.

Association of Intensive Blood Pressure Control and Kidney Disease Progression in Nondiabetic Patients With Chronic Kidney Disease

The optimal blood pressure (BP) target remains debated in nondiabetic patients with chronic kidney disease (CKD). To compare intensive BP control (<130/80 mm Hg) with standard BP control (<140/90 mm Hg) on major renal outcomes in patients with CKD without diabetes. Searches of PubMed, MEDLINE, Embase, and Cochrane Library for publications up to March 24, 2016. Randomized clinical trials that compared an intensive vs a standard BP target in nondiabetic adults with CKD, reporting changes in glomerular filtration rate (GFR), doubling of serum creatinine level, 50% reduction in GFR, end-stage renal disease (ESRD), or all-cause mortality. Random-effects meta-analyses for pooling effect measures. Meta-regression and subgroup analyses for exploring heterogeneity. Differences in annual rate of change in GFR were expressed as mean differences with 95% CIs. Differences in doubling of serum creatinine or 50% reduction in GFR, ESRD, composite renal outcome, and all-cause mortality were expressed as risk ratios (RRs) with 95% CIs. We identified 9 trials with 8127 patients and a median follow-up of 3.3 years. Compared with standard BP control, intensive BP control did not show a significant difference on the annual rate of change in GFR (mean difference, 0.07; 95% CI, -0.16 to 0.29 mL/min/1.73 m2/y), doubling of serum creatinine level or 50% reduction in GFR (RR, 0.99; 95% CI, 0.76-1.29), ESRD (RR, 0.96; 95% CI, 0.78-1.18), composite renal outcome (RR, 0.99; 95% CI, 0.81-1.21), or all-cause mortality (RR, 0.95; 95% CI, 0.66-1.37). Nonblacks and patients with higher levels of proteinuria showed a trend of lower risk of kidney disease progression with intensive BP control. Targeting BP below the current standard did not provide additional benefit for renal outcomes compared with standard treatment during a follow-up of 3.3 years in patients with CKD without diabetes. However, nonblack patients or those with higher levels of proteinuria might benefit from the intensive BP-lowering treatments.

Abstract 003: Personalizing the Intensity of Blood Pressure Control: Modeling the Heterogeneity of Risks and Benefits From the SPRINT Trial

Introduction: In SPRINT (Systolic blood PRessure INtervention Trial), non-diabetic patients with hypertension at high cardiovascular risk treated with intensive blood pressure (BP) control (&lt;120mmHg) had fewer major adverse cardiovascular events (MACE) and all-cause deaths but higher rates of serious adverse events (SAE) compared with patients treated with standard BP control (&lt;140mmHg). However, the degree of benefit or harm for an individual patient could vary due to heterogeneity in treatment effect. Methods: Using patient-level data from SPRINT, we developed predictive models for benefit (freedom from death or MACE) and harm (increased SAE) to allow for individualized BP treatment goals based on projected risk-benefit for each patient. Interactions between candidate variable and treatment were evaluated in the models to identify differential treatment effects. We performed 10 fold cross-validation for both the models. Results: Among 9361 patients, 8606 (92%) patients had no MACE or death event (benefit) and 3529 (38%) patients had a SAE (harm) over a median follow-up of 3.3 years. The benefit model showed good discrimination (c-index= 0.72; cross-validated c-index= 0.72) with treatment interactions of age, sex, and baseline systolic BP (Figure A), with more benefit of intensive BP treatment in patients who are older, male, and have lower baseline SBP. The SAE risk model showed moderate discrimination (c-index=0.66; cross-validated c-index= 0.65) with a treatment interaction of baseline renal function (Figure B), indicating less harm of intensive treatment in patients with a higher baseline creatinine. The mean predicted absolute benefit of intensive BP treatment was of 2.2% ± 2.5% compared with standard treatment, but ranged from 10.7% lower benefit to 17% greater benefit in individual patients. Similarly, mean predicted absolute harm with intensive treatment was 1.0% ± 1.9%, but ranged from 15.9% lesser harm to 4.9% more harm. Conclusion: Among non-diabetic patients with hypertension at high cardiovascular risk, we developed prediction models using basic clinical data that can identify patients with higher likelihood of benefit vs. harm with BP treatment strategies. These models could be used to tailor the treatment approach based on the projected risk and benefit for each unique patient.

Abstract 240: Prevalence of Intense Systolic Blood Pressure Control in Unselected Real World Non-Diabetic Hypertensive Patients

Background: Recent data from SPRINT trial demonstrated that, intense systolic blood pressure (ISBP) control to &lt;120 mm Hg was associated with lower cardiovascular morbidity and mortality, compared to standard systolic BP (St-SBP) control to &lt;140 mm Hg. We sought to determine current trend in the clinical practice in terms of intense SBP control. Methods: Electronic medical records from 3 different ambulatory clinics were reviewed to identify hypertensive patients with at least 3 consecutive clinic visits. Patients with diabetes, with &lt;3 clinic visits, end-stage renal failure, and end stage liver failure were excluded. Cohort was categorized in to ISBP group and St-SBP group, when more than 50% of the clinic encounters had SBP ≤ 120 mm HG and &gt; 120 mm Hg respectively. Results: 1644 non diabetic patients with HTN included in the analysis. 1389 (84.5%) patients had St-SBP control whereas only 255 (15.5%) patients had ISBP control. ISBP group had significantly lower mean (±SD) SBP compared to St-SBP group; 116(±6.4) mm Hg vs. 136(±11.6) mm Hg respectively; P&lt;0.0001. Baseline characteristics shown in table 1. ISBP group and St-SBP group had similar comorbid profile, except slightly greater prevalence of COPD in ISBP 46 (18.0%) vs 165 (11.9%); P=0.007. Conclusion: There is significant variation in SBP control in non-diabetic hypertensive patients in clinical practice, despite comparable comorbid profile. Furthermore, ISBP control is not a common practice in real world. Quality improvement measures should focus on promoting ISBP control in non-diabetic hypertensive patients.

In adults ≥75 years of age with hypertension, intensive vs standard BP-lowering treatment reduced CV events.

Source Citation Williamson JD, Supiano MA, Applegate WB, et al; SPRINT Research Group. Intensive vs standard blood pressure control and cardiovascular disease outcomes in adults aged ≥ 75 years: a ...

Prognostic enrichment design in clinical trials for autosomal dominant polycystic kidney disease: the HALT-PKD clinical trial

Patients with mild autosomal dominant polycystic kidney disease (ADPKD) are less likely to be informative in randomized clinical trials (RCTs). We previously developed an imaging classification of ADPKD (typical diffuse cyst distribution Class 1A-E and atypical cyst distribution Class 2) for prognostic enrichment design in RCTs. We investigated whether using this classification would have increased the power to detect a beneficial treatment effect of rigorous blood pressure (BP) control on HALT-PKD participants with early disease (Study A). Post hoc analysis of the early disease HALT-PKD study, an RCT that studied the effect of rigorous versus standard BP control on rates of total kidney volume (TKV) increase and estimated glomerular filtration rate (eGFR) decline in ADPKD patients with eGFR >60 mL/min/1.73 m2. Five hundred and fifty-one patients were classified by two observers (98.2% agreement) into Class 1A (6.2%), 1B (20.3%), 1C (34.1%), 1D (22.1%), 1E (11.8%) and 2 (5.4%). The TKV increase and eGFR decline became steeper from Class 1A through 1E. Rigorous BP control had been shown to be associated with slower TKV increase, without a significant overall effect on the rate of eGFR decline (faster in the first 4 months and marginally slower thereafter). Merging Classes 1A and 2 (lowest severity), 1B and 1C (intermediate severity) and 1D and 1E (highest severity) detected stronger beneficial effects on TKV increase and eGFR decline in Class 1D and E with a smaller number of patients. Strategies for prognostic enrichment, such as image classification, should be used in the design of RCTs for ADPKD to increase their power and reduce their cost.