Dataset Information

The Impact of Frailty on the Effectiveness and Safety of Intensive Glucose Control and Blood Pressure-Lowering Therapy for People With Type 2 Diabetes: Results From the ADVANCE Trial.

ABSTRACT:

Objective

To develop a frailty index (FI) and explore the relationship of frailty to subsequent adverse outcomes on the effectiveness and safety of more intensive control of both blood glucose and blood pressure (BP), among participants with type 2 diabetes in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial.

Research design and methods

Cox proportional hazard models were used to estimate the effectiveness and safety of intensive glucose control and BP intervention according to frailty (defined as FI >0.21) status. The primary outcomes were macro- and microvascular events. The secondary outcomes were all-cause mortality, cardiovascular mortality, severe hypoglycemia, and discontinuation of BP treatment due to hypotension/dizziness.

Results

There were 11,140 participants (mean age, 65.8 years; 42.5% women, 25.7% frail). Frailty was an independent predictor of all primary outcomes and secondary outcomes. The effect of intensive glucose treatment on primary outcomes showed some evidence of attenuation in the frail: hazard ratios for combined major macro- and microvascular events 1.03 (95% CI 0.90-1.19) in the frail versus 0.84 (95% CI 0.74-0.94) in the nonfrail (P = 0.02). A similar trend was observed with BP intervention. Severe hypoglycemia rates (per 1,000 person-years) were higher in the frail: 8.39 (6.15-10.63) vs. 4.80 (3.84-5.76) in nonfrail (P < 0.001). There was no significant difference in discontinuation of BP treatment between frailty groups.

Conclusions

It was possible to retrospectively estimate frailty in a trial population, and this FI identified those at higher risk of poor outcomes. Participants with frailty had some attenuation of benefit from intensive glucose-lowering and BP-lowering treatments.

SUBMITTER: Nguyen TN

PROVIDER: S-EPMC8323181 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Publications

The Impact of Frailty on the Effectiveness and Safety of Intensive Glucose Control and Blood Pressure-Lowering Therapy for People With Type 2 Diabetes: Results From the ADVANCE Trial.

Nguyen Tu N TN Harris Katie K Woodward Mark M Chalmers John J Cooper Mark M Hamet Pavel P Harrap Stephen S Heller Simon S MacMahon Stephen S Mancia Giuseppe G Marre Michel M Poulter Neil N Rogers Anthony A Williams Bryan B Zoungas Sophia S Chow Clara K CK Lindley Richard I RI

Diabetes care 20210525 7

<h4>Objective</h4>To develop a frailty index (FI) and explore the relationship of frailty to subsequent adverse outcomes on the effectiveness and safety of more intensive control of both blood glucose and blood pressure (BP), among participants with type 2 diabetes in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial.<h4>Research design and methods</h4>Cox proportional hazard models were used to estimate the effectiveness a ...[more]

PMID: 34035077

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Project description:BackgroundEpidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes. We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors.MethodsIn this randomized study, 10,251 patients (mean age, 62.2 years) with a median glycated hemoglobin level of 8.1% were assigned to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level from 7.0 to 7.9%). Of these patients, 38% were women, and 35% had had a previous cardiovascular event. The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The finding of higher mortality in the intensive-therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up.ResultsAt 1 year, stable median glycated hemoglobin levels of 6.4% and 7.5% were achieved in the intensive-therapy group and the standard-therapy group, respectively. During follow-up, the primary outcome occurred in 352 patients in the intensive-therapy group, as compared with 371 in the standard-therapy group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P=0.16). At the same time, 257 patients in the intensive-therapy group died, as compared with 203 patients in the standard-therapy group (hazard ratio, 1.22; 95% CI, 1.01 to 1.46; P=0.04). Hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group (P<0.001).ConclusionsAs compared with standard therapy, the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events. These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.)

Project description:BackgroundIntensive glucose lowering has previously been shown to increase mortality among persons with advanced type 2 diabetes and a high risk of cardiovascular disease. This report describes the 5-year outcomes of a mean of 3.7 years of intensive glucose lowering on mortality and key cardiovascular events.MethodsWe randomly assigned participants with type 2 diabetes and cardiovascular disease or additional cardiovascular risk factors to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level of 7 to 7.9%). After termination of the intensive therapy, due to higher mortality in the intensive-therapy group, the target glycated hemoglobin level was 7 to 7.9% for all participants, who were followed until the planned end of the trial.ResultsBefore the intensive therapy was terminated, the intensive-therapy group did not differ significantly from the standard-therapy group in the rate of the primary outcome (a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) (P=0.13) but had more deaths from any cause (primarily cardiovascular) (hazard ratio, 1.21; 95% confidence interval [CI], 1.02 to 1.44) and fewer nonfatal myocardial infarctions (hazard ratio, 0.79; 95% CI, 0.66 to 0.95). These trends persisted during the entire follow-up period (hazard ratio for death, 1.19; 95% CI, 1.03 to 1.38; and hazard ratio for nonfatal myocardial infarction, 0.82; 95% CI, 0.70 to 0.96). After the intensive intervention was terminated, the median glycated hemoglobin level in the intensive-therapy group rose from 6.4% to 7.2%, and the use of glucose-lowering medications and rates of severe hypoglycemia and other adverse events were similar in the two groups.ConclusionsAs compared with standard therapy, the use of intensive therapy for 3.7 years to target a glycated hemoglobin level below 6% reduced 5-year nonfatal myocardial infarctions but increased 5-year mortality. Such a strategy cannot be recommended for high-risk patients with advanced type 2 diabetes. (Funded by the National Heart, Lung and Blood Institute; ClinicalTrials.gov number, NCT00000620.).

Project description:BackgroundLimited data are available to guide the choice of a target for the systolic blood-pressure level when treating acute hypertensive response in patients with intracerebral hemorrhage.MethodsWe randomly assigned eligible participants with intracerebral hemorrhage (volume, <60 cm(3)) and a Glasgow Coma Scale (GCS) score of 5 or more (on a scale from 3 to 15, with lower scores indicating worse condition) to a systolic blood-pressure target of 110 to 139 mm Hg (intensive treatment) or a target of 140 to 179 mm Hg (standard treatment) in order to test the superiority of intensive reduction of systolic blood pressure to standard reduction; intravenous nicardipine to lower blood pressure was administered within 4.5 hours after symptom onset. The primary outcome was death or disability (modified Rankin scale score of 4 to 6, on a scale ranging from 0 [no symptoms] to 6 [death]) at 3 months after randomization, as ascertained by an investigator who was unaware of the treatment assignments.ResultsAmong 1000 participants with a mean (±SD) systolic blood pressure of 200.6±27.0 mm Hg at baseline, 500 were assigned to intensive treatment and 500 to standard treatment. The mean age of the patients was 61.9 years, and 56.2% were Asian. Enrollment was stopped because of futility after a prespecified interim analysis. The primary outcome of death or disability was observed in 38.7% of the participants (186 of 481) in the intensive-treatment group and in 37.7% (181 of 480) in the standard-treatment group (relative risk, 1.04; 95% confidence interval, 0.85 to 1.27; analysis was adjusted for age, initial GCS score, and presence or absence of intraventricular hemorrhage). Serious adverse events occurring within 72 hours after randomization that were considered by the site investigator to be related to treatment were reported in 1.6% of the patients in the intensive-treatment group and in 1.2% of those in the standard-treatment group. The rate of renal adverse events within 7 days after randomization was significantly higher in the intensive-treatment group than in the standard-treatment group (9.0% vs. 4.0%, P=0.002).ConclusionsThe treatment of participants with intracerebral hemorrhage to achieve a target systolic blood pressure of 110 to 139 mm Hg did not result in a lower rate of death or disability than standard reduction to a target of 140 to 179 mm Hg. (Funded by the National Institute of Neurological Disorders and Stroke and the National Cerebral and Cardiovascular Center; ATACH-2 ClinicalTrials.gov number, NCT01176565 .).

Project description:Background and objectiveThe clinical effect of renal impairment on intracerebral hemorrhage (ICH) is unknown. This study sought to assess whether estimated glomerular filtration rate (eGFR) affects clinical outcomes or modifies the efficacy of intensive systolic blood pressure (BP) control (target, 110-139 mm Hg) against the standard (target, 140-179 mm Hg) among patients with ICH.MethodsWe conducted post hoc analyses of ATACH-2, a randomized, 2-group, open-label trial. The baseline eGFR of each eligible patient was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. The outcome of interest was death or disability at 90 days. Multivariate logistic regression models were used for analysis.ResultsAmong the 1,000 patients randomized, 974 were analyzed. The median baseline eGFR was 88 (interquartile range, 68, 99) mL/min/1.73 m2; 451 (46.3%), 363 (37.3%), and 160 (16.4%) patients had baseline eGFR values of ≥90, 60-89, and <60 mL/min/1.73 m2, respectively. Compared with normal eGFR (≥90 mL/min/1.73 m2), higher odds of death or disability were noted among those with eGFR values of <60 mL/min/1.73 m2 (adjusted odds ratio [OR], 2.02; 95% confidence interval [CI], 1.25-3.26) but not among those with eGFR values of 60-89 mL/min/1.73 m2 (OR, 1.01; 95% CI, 0.70-1.46). The odds of death or disability were significantly higher in the intensive arm among patients with decreased eGFR; the ORs were 0.89 (95% CI, 0.55-1.44), 1.13 (0.68-1.89), and 3.60 (1.47-8.80) in patients with eGFR values of ≥90, 60-89, and <60 mL/min/1.73 m2, respectively (p for interaction = 0.02).DiscussionDecreased eGFR is associated with unfavorable outcomes following ICH. The statistically significant interaction between the eGFR group and treatment assignment raised safety concerns for the intensive BP-lowering therapy among patients with renal impairment.Trial registration informationClinicaltrials.gov identifier: NCT01176565.Classification of evidenceThis study provides Class II evidence that in spontaneous ICH, decreased eGFR identifies patients at risk of death or disability following intensive BP control.

Project description:Importance:Among high-risk patients with hypertension, targeting a systolic blood pressure of 120 mm Hg reduces cardiovascular morbidity and mortality compared with a higher target. However, intensive blood pressure management incurs additional costs from treatment and from adverse events. Objective:To evaluate the incremental cost-effectiveness of intensive blood pressure management compared with standard management. Design, Setting, and Participants:This cost-effectiveness analysis conducted from September 2015 to August 2016 used a Markov cohort model to estimate cost-effectiveness of intensive blood pressure management among 68-year-old high-risk adults with hypertension but not diabetes. We used the Systolic Blood Pressure Intervention Trial (SPRINT) to estimate treatment effects and adverse event rates. We used Centers for Disease Control and Prevention Life Tables to project age- and cause-specific mortality, calibrated to rates reported in SPRINT. We also used population-based observational data to model development of heart failure, myocardial infarction, stroke, and subsequent mortality. Costs were based on published sources, Medicare data, and the National Inpatient Sample. Interventions:Treatment of hypertension to a systolic blood pressure goal of 120 mm Hg (intensive management) or 140 mm Hg (standard management). Main Outcomes and Measures:Lifetime costs and quality-adjusted life-years (QALYs), discounted at 3% annually. Results:Standard management yielded 9.6 QALYs and accrued $155?261 in lifetime costs, while intensive management yielded 10.5 QALYs and accrued $176?584 in costs. Intensive blood pressure management cost $23?777 per QALY gained. In a sensitivity analysis, serious adverse events would need to occur at 3 times the rate observed in SPRINT and be 3 times more common in the intensive management arm to prefer standard management. Conclusions and Relevance:Intensive blood pressure management is cost-effective at typical thresholds for value in health care and remains so even with substantially higher adverse event rates.

Dataset Information

The Impact of Frailty on the Effectiveness and Safety of Intensive Glucose Control and Blood Pressure-Lowering Therapy for People With Type 2 Diabetes: Results From the ADVANCE Trial.

Objective

Research design and methods

Results

Conclusions

Publications

The Impact of Frailty on the Effectiveness and Safety of Intensive Glucose Control and Blood Pressure-Lowering Therapy for People With Type 2 Diabetes: Results From the ADVANCE Trial.

Similar Datasets

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