Intensive versus standard blood pressure control in type 2 diabetes: a restricted mean survival time analysis of a randomised controlled trial.
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ABSTRACT: Background
Restricted mean survival time analysis offers an intuitive and robust summary of treatment effect compared with HRs.Objective
To examine the effect of intensive versus standard blood pressure (BP) control on death or cardiovascular events in type 2 diabetes.Design
Secondary analysis of the Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial.Setting
77 sites in the USA and Canada.Participants
4733 adults with type 2 diabetes at high risk for cardiovascular events.Interventions
Systolic BP target <120 mm Hg (n=2371) versus <140 mm Hg (n=2362).Measurements
Composite endpoint of death, non-fatal myocardial infarction or non-fatal stroke.Results
The mean event-free survival time over 5 years (1825 days) was similar between intensive and standard BP control (1716 vs 1714 days; mean difference, 1.3 (95% CI -18.1 to 20.7) days). However, intensive BP treatment was more beneficial for those assigned to standard glycaemic control (1725 vs 1697 days; mean difference, 28.1 (95% CI 0.4 to 55.9) days), but not for those assigned to intensive glycaemic control (1706 vs 1731 days; mean difference, -25.2 (95% CI -52.3 to 1.9) days) (p=0.008 for interaction). In subgroup analysis, the mean event-free survival time difference between intensive and standard BP treatment was -76.0 (95% CI -131.8 to -20.3) days for those with cognitive impairment and 21.8 (95% CI -24.0 to 67.5) days for those with normal cognitive function (p=0.008 for interaction). The effect was not different by age, sex and baseline cardiovascular disease status.Conclusions
Intensive BP treatment may reduce death and cardiovascular events among patients with type 2 diabetes receiving standard glycaemic treatment and without cognitive impairment.Trial registration number
NCT00000620; Post-results.
SUBMITTER: Shi S
PROVIDER: S-EPMC8438933 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In 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.We 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.We 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.In 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 .).
| S-EPMC5708850 | biostudies-literature
Project description:Background/objectivesRestricted mean survival time (RMST) summarizes treatment effect in terms of a gain or loss in the event-free days. It remains uncertain whether communicating treatment benefit and harm using RMST-based summary is more effective than conventional summary based on absolute and relative risk reduction. We compared the effect of RMST-based approach and conventional approach on decisional conflict using an example of intensive versus standard blood pressure-lowering strategies.DesignOn-line survey.SettingA convenience sample of patients in the United States.ParticipantsTwo hundred adults aged 65 and older with hypertension requiring anti-hypertensive treatment (response rate 85.5%).InterventionsParticipants were randomly assigned to either RMST-based summary or conventional summary about the benefit and harm of blood pressure-lowering strategies.MeasurementsDecisional Conflict Scale (DCS), ranging from 0 (no conflict) to 100 (high conflict), and preference for intensive blood pressure-lowering strategy.ResultsParticipants assigned to RMST-based approach (n = 100) and conventional approach (n = 100) had similar age (mean [standard deviation, SD]: 72.3 [5.6] vs 72.8 [5.5] years) and proportions of female (50 [50.0%] vs 61 [61.0%]) and white race (92 [92.0%] vs 92 [92.0%]). The mean (SD) DCS score was 25.2 (15.0) for RMST-based approach and 25.6 (14.1) for conventional approach (p = 0.84). The number (%) of participants who preferred intensive strategy was 10 (10.0%) for RMST-based approach and 14 (14.0%) for conventional approach (p = 0.52). The results were consistent in subgroups defined by age, sex, education level, cardiovascular disease status, and predicted mortality risk categories.ConclusionIn a sample of relatively healthy older adults with hypertension, RMST-based approach was as effective as conventional approach on decisional conflict about choosing a blood pressure-lowering strategy. This study provides proof-of-concept evidence that RMST-based approach can be used in conjunction with absolute and relative risk reduction for communicating treatment benefit and harm in a decision aid.
| S-EPMC8373742 | biostudies-literature
Project description:BackgroundThe most appropriate targets for systolic blood pressure to reduce cardiovascular morbidity and mortality among persons without diabetes remain uncertain.MethodsWe randomly assigned 9361 persons with a systolic blood pressure of 130 mm Hg or higher and an increased cardiovascular risk, but without diabetes, to a systolic blood-pressure target of less than 120 mm Hg (intensive treatment) or a target of less than 140 mm Hg (standard treatment). The primary composite outcome was myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes.ResultsAt 1 year, the mean systolic blood pressure was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the standard-treatment group. The intervention was stopped early after a median follow-up of 3.26 years owing to a significantly lower rate of the primary composite outcome in the intensive-treatment group than in the standard-treatment group (1.65% per year vs. 2.19% per year; hazard ratio with intensive treatment, 0.75; 95% confidence interval [CI], 0.64 to 0.89; P<0.001). All-cause mortality was also significantly lower in the intensive-treatment group (hazard ratio, 0.73; 95% CI, 0.60 to 0.90; P=0.003). Rates of serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure, but not of injurious falls, were higher in the intensive-treatment group than in the standard-treatment group.ConclusionsAmong patients at high risk for cardiovascular events but without diabetes, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, resulted in lower rates of fatal and nonfatal major cardiovascular events and death from any cause, although significantly higher rates of some adverse events were observed in the intensive-treatment group. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01206062.).
| S-EPMC4689591 | biostudies-literature
Project description:Intensive systolic blood pressure (SBP) control improved outcomes in SPRINT (Systolic Blood Pressure Intervention Trial). Our objective was to expand on reported findings by analysis of baseline characteristics, primary outcomes, adverse events, follow-up blood pressure, and medication use differences by baseline SBP (tertile 1 [T1], <132; tertile 2 [T2], 132-145; and tertile 3 [T3], >145 mm Hg). Participants with higher baseline SBP tertile were more often women and older, had higher cardiovascular risk, and lower utilization of antihypertensive medications, statins, and aspirin. Achieved SBP in both treatment arms was slightly higher in T2 and T3 compared with T1 and fewer in the T3 groups achieved SBP targets compared with T1 and T2 groups. The primary composite outcome with intensive versus standard SBP treatment was reduced by 30% in T1, 23% in T2, and 17% in T3 with no evidence of an interaction (P=0.77). Event rates were lower in the intensive arm, and there was no evidence that this benefit differed by SBP tertile. There was no difference in the hazard for serious adverse events in any of the 3 tertiles. Medication utilization differed across the SBP tertiles at baseline with a lesser percentage of diuretics and angiotensin-converting enzyme inhibitors/angiotensin receptor blocker drugs in the higher tertiles-a finding that reversed during the trial. The beneficial effects of intensive SBP lowering were not modified by the level of baseline SBP. Within the parameters of this population, these findings add support for clinicians to treat blood pressure to goal irrespective of baseline SBP.
| S-EPMC5945323 | biostudies-literature
Project description:BackgroundIn 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.MethodsWe 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.ResultsAt 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.ConclusionsAmong 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.).
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Project description:For a study with an event time as the endpoint, its survival function contains all the information regarding the temporal, stochastic profile of this outcome variable. The survival probability at a specific time point, say t, however, does not transparently capture the temporal profile of this endpoint up to t. An alternative is to use the restricted mean survival time (RMST) at time t to summarize the profile. The RMST is the mean survival time of all subjects in the study population followed up to t, and is simply the area under the survival curve up to t. The advantages of using such a quantification over the survival rate have been discussed in the setting of a fixed-time analysis. In this article, we generalize this approach by considering a curve based on the RMST over time as an alternative summary to the survival function. Inference, for instance, based on simultaneous confidence bands for a single RMST curve and also the difference between two RMST curves are proposed. The latter is informative for evaluating two groups under an equivalence or noninferiority setting, and quantifies the difference of two groups in a time scale. The proposal is illustrated with the data from two clinical trials, one from oncology and the other from cardiology.
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Project description:In clinical or epidemiological follow-up studies, methods based on time scale indicators such as the restricted mean survival time (RMST) have been developed to some extent. Compared with traditional hazard rate indicator system methods, the RMST is easier to interpret and does not require the proportional hazard assumption. To date, regression models based on the RMST are indirect or direct models of the RMST and baseline covariates. However, time-dependent covariates are becoming increasingly common in follow-up studies. Based on the inverse probability of censoring weighting (IPCW) method, we developed a regression model of the RMST and time-dependent covariates. Through Monte Carlo simulation, we verified the estimation performance of the regression parameters of the proposed model. Compared with the time-dependent Cox model and the fixed (baseline) covariate RMST model, the time-dependent RMST model has a better prediction ability. Finally, an example of heart transplantation was used to verify the above conclusions.
| S-EPMC9545070 | biostudies-literature
Project description:Restricted mean survival time (RMST) is often of great clinical interest in practice. Several existing methods involve explicitly projecting out patient-specific survival curves using parameters estimated through Cox regression. However, it would often be preferable to directly model the restricted mean for convenience and to yield more directly interpretable covariate effects. We propose generalized estimating equation methods to model RMST as a function of baseline covariates. The proposed methods avoid potentially problematic distributional assumptions pertaining to restricted survival time. Unlike existing methods, we allow censoring to depend on both baseline and time-dependent factors. Large sample properties of the proposed estimators are derived and simulation studies are conducted to assess their finite sample performance. We apply the proposed methods to model RMST in the absence of liver transplantation among end-stage liver disease patients. This analysis requires accommodation for dependent censoring since pre-transplant mortality is dependently censored by the receipt of a liver transplant.
| S-EPMC5565738 | biostudies-literature
Project description:BackgroundTreatment effect is typically summarized in terms of relative risk reduction or number needed to treat ("conventional effect summary"). Restricted mean survival time (RMST) summarizes treatment effect in terms of a gain or loss in event-free days. Older adults' preference between the two effect summary measures has not been studied.MethodsWe conducted a mixed methods study using a quantitative survey and qualitative semi-structured interviews. For the survey, we enrolled 102 residents with hypertension at five senior housing facilities (mean age 81.3 years, 82 female, 95 white race). We randomly assigned respondents to either RMST-based (n = 49) or conventional decision aid (n = 53) about the benefits and harms of intensive versus standard blood pressure-lowering strategies and compared decision conflict scale (DCS) responses (range: 0 [no conflict] to 100 [maximum conflict]; <25 is associated with implementing decisions). We used a purposive sample of 23 survey respondents stratified by both their random assignment and DCS from the survey. Inductive qualitative thematic analysis explored complementary perspectives on preferred ways of summarizing treatment effects.ResultsThe mean (standard deviation) total DCS was 22.0 (14.3) for the conventional decision aid group and 16.7 (14.1) for the RMST-based decision aid group (p = 0.06), but the proportion of participants with a DCS <25 was higher in the RMST-based group (26 [49.1%] vs 34 [69.4%]; p = 0.04). Qualitative interviews suggested that, regardless of effect summary measure, older individuals' preference depended on their ability to clearly comprehend quantitative information, clarity of presentation in the visual aid, and inclusion of desired information.ConclusionsWhen choosing a blood pressure-lowering strategy, older adults' perceived uncertainty may be reduced with a time-based effect summary, although our study was underpowered to detect a statistically significant difference. Given highly variable individual preferences, it may be useful to present both conventional and RMST-based information in decision aids.
| S-EPMC9957827 | biostudies-literature
Project description:BackgroundResults from the Systolic Blood Pressure Intervention Trial (SPRINT) showed that intensive control of systolic blood pressure significantly reduced the occurrence of mild cognitive impairment, but not probable dementia. We investigated the effects of intensive lowering of systolic blood pressure on specific cognitive functions in a preplanned substudy of participants from SPRINT.MethodsSPRINT was an open-label, multicentre, randomised controlled trial undertaken at 102 sites, including academic medical centres, Veterans Affairs medical centres, hospitals, and independent clinics, in the USA and Puerto Rico. Participants were adults aged 50 years or older with systolic blood pressure higher than 130 mm Hg, but without diabetes, history of stroke, or dementia. Participants were randomly assigned (1:1) to a systolic blood pressure goal of less than 120 mm Hg (intensive treatment) versus less than 140 mm Hg (standard treatment). All major classes of antihypertensive agents were included. A subgroup of randomly assigned participants including, but not limited to, participants enrolled in an MRI substudy was then selected for a concurrent substudy of cognitive function (target 2800 participants). Each individual was assessed with a screening cognitive test battery and an extended cognitive test battery at baseline and biennially during the planned 4-year follow-up. The primary outcomes for this substudy were standardised composite scores for memory (Logical Memory I and II, Modified Rey-Osterrieth Complex Figure [immediate recall], and Hopkins Verbal Learning Test-Revised [delayed recall]) and processing speed (Trail Making Test and Digit Symbol Coding). SPRINT was registered with ClinicalTrials.gov, NCT01206062.FindingsFrom Nov 23, 2010, to Dec 28, 2012, 2921 participants (mean age 68·4 years [SD 8·6], 1080 [37%] women) who had been randomly assigned in SPRINT were enrolled in the substudy (1448 received intensive treatment and 1473 received standard treatment). SPRINT was terminated early due to benefit observed in the primary outcome (composite of cardiovascular events). After a median follow-up of 4·1 years (IQR 3·7-5·8), there was no between-group difference in memory, with an annual decline in mean standardised domain score of -0·005 (95% CI -0·010 to 0·001) in the intensive treatment group and -0·001 (-0·006 to 0·005) in the standard treatment group (between-group difference -0·004, 95% CI -0·012 to 0·004; p=0·33). Mean standardised processing speed domain scores declined more in the intensive treatment group (between-group difference -0·010, 95% CI -0·017 to -0·002; p=0·02), with an annual decline of -0·025 (-0·030 to -0·019) for the intensive treatment group and -0·015 (-0·021 to 0·009) for the standard treatment group.InterpretationIntensive treatment to lower systolic blood pressure did not result in a clinically relevant difference compared with standard treatment in memory or processing speed in a subgroup of participants from SPRINT. The effect of blood pressure lowering might not be evident in specific domains of cognitive function, but instead distributed across multiple domains.FundingNational Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Aging, National Institute of Neurological Disorders and Stroke, and the Alzheimer's Association.
| S-EPMC7714000 | biostudies-literature