Treatment of Type 1 Diabetes: Synopsis of the 2017 American Diabetes Association Standards of Medical Care in Diabetes

Description: The American Diabetes Association (ADA) annually updates Standards of Medical Care in Diabetes to provide clinicians, patients, researchers, payers, and other interested parties with evidence-based recommendations for the diagnosis and management of patients with diabetes. Methods: For the 2017 Standards of Care, the ADA Professional Practice Committee did MEDLINE searches from 1 January 2016 to November 2016 to add, clarify, or revise recommendations on the basis of new evidence. The committee rated the recommendations as A, B, or C, depending on the quality of evidence, or E for expert consensus or clinical experience. The Standards of Care were reviewed and approved by the Executive Committee of the ADA Board of Directors, which includes health care professionals, scientists, and laypersons. Feedback from the larger clinical community informed revisions. Recommendation: This synopsis focuses on recommendations from the 2017 Standards of Care about monitoring and pharmacologic approaches to glycemic management for type 1 diabetes.

Benefits and Risks of Antithrombotic Therapy in Essential Thrombocythemia: A Systematic Review: Annals of Internal Medicine: Vol 167, No 3

Background: Patients with essential thrombocythemia (ET) are at high risk for both thrombosis and hemorrhage. Purpose: To evaluate the risks and benefits of antithrombotic therapy in adults with ET. Data Sources: Multiple databases, including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, through 4 March 2017. Study Selection: Randomized and observational studies of antiplatelet or anticoagulant therapy, published in any language and reporting thrombotic or hemorrhagic events. Data Extraction: Two reviewers independently extracted data, assessed risk of bias, and graded certainty of evidence. Data Synthesis: No relevant randomized trials were identified. Twenty-four observational studies (18 comparative and 6 single-group) involving 6153 patients followed for 31 711 patient-years were reviewed; most were deemed to have high risk of bias. Most patients receiving antiplatelet therapy (3613 of 4527 [80%]) received low-dose aspirin (50 to 150 mg/d); 914 (20%) received high-dose aspirin (300 to 600 mg/d), dipyridamole, or other agents. Overall, findings were inconsistent and imprecise. The reported incidence rates of thrombosis, any bleeding, and major bleeding without antiplatelet therapy ranged from 5 to 110 (median, 20), from 3 to 39 (median, 8), and from 2 to 53 (median, 6) cases per 1000 patient-years, respectively. The reported relative risks for thrombosis, any bleeding, and major bleeding with antiplatelet therapy compared with none ranged from 0.26 to 3.48 (median, 0.74), from 0.48 to 11.04 (median, 1.95), and from 0.48 to 5.17 (median, 1.30), respectively. Certainty of evidence was rated low or very low for all outcomes. Limitation: No randomized trials, no extractable data on anticoagulants, lack of uniform bleeding definitions, and systematic reporting of outcomes. Conclusion: Available evidence about the risk–benefit ratio of antiplatelet therapy in adults with ET is highly uncertain. Primary Funding Source: Regional Medical Associates. (PROSPERO: CRD42015027051)

Detecting Heterogeneous Treatment Effects to Guide Personalized Blood Pressure Treatment: A Modeling Study of Randomized Clinical Trials: Annals of Internal Medicine: Vol 166, No 5

Background: Two recent randomized trials produced discordant results when testing the benefits and harms of treatment to reduce blood pressure (BP) in patients with cardiovascular disease (CVD). Objective: To perform a theoretical modeling study to identify whether large, clinically important differences in benefit and harm among patients (heterogeneous treatment effects [HTEs]) can be hidden in, and explain discordant results between, treat-to-target BP trials. Design: Microsimulation. Data Sources: Results of 2 trials comparing standard (systolic BP target <140 mm Hg) with intensive (systolic BP target <120 mm Hg) BP treatment and data from the National Health and Nutrition Examination Survey (2013 to 2014). Target Population: U.S. adults. Time Horizon: 5 years. Perspective: Societal. Intervention: BP treatment. Outcome Measures: CVD events and mortality. Results of Base-Case Analysis: Clinically important HTEs could explain differences in outcomes between 2 trials of intensive BP treatment, particularly diminishing benefit with each additional BP agent (for example, adding a second agent reduces CVD risk [hazard ratio, 0.61], but adding a fourth agent to a third has no benefit) and increasing harm at low diastolic BP. Results of Sensitivity Analysis: Conventional treat-to-target trial designs had poor (<5%) statistical power to detect the HTEs, despite large samples (n > 20 000), and produced biased effect estimates. In contrast, a trial with sequential randomization to more intensive therapy achieved greater than 80% power and unbiased HTE estimates, despite small samples (n = 3500). Limitations: The HTEs as a function of the number of BP agents only were explored. Simulated aggregate data from the trials were used as model inputs because individual-participant data were not available. Conclusion: Clinically important heterogeneity in intensive BP treatment effects remains undetectable in conventional trial designs but can be detected in sequential randomization trial designs. Primary Funding Source: National Institutes of Health and U.S. Department of Veterans Affairs.

Comparative Effectiveness of Management Strategies for Renal Artery Stenosis: An Updated Systematic Review: Annals of Internal Medicine: Vol 165, No 9

Background: Atherosclerotic renal artery stenosis (ARAS) is associated with high blood pressure (BP), decreased kidney function, renal replacement therapy (RRT), and death. Purpose: To compare benefits and harms of percutaneous transluminal renal angioplasty with stent placement (PTRAS) versus medical therapy alone in adults with ARAS. Data Sources: MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from 1993 to 16 March 2016; gray literature; and prior systematic reviews. Study Selection: Randomized, controlled trials (RCTs); nonrandomized, comparative studies (NRCSs); single-group studies; and selected case reports that reported all-cause and cardiovascular mortality, RRT, kidney function, BP, and adverse events. Data Extraction: Six researchers extracted data on design, interventions, outcomes, and study quality into a Web-based database. Data Synthesis: Eighty-three studies met eligibility criteria. In 5 of 7 RCTs, PTRAS and medical therapy led to similar BP control in patients with ARAS, and no RCTs showed statistically significant differences in kidney function, mortality, RRT, cardiovascular events, or pulmonary edema. Eight NRCSs had more variable results, finding mostly no significant differences in mortality, RRT, or cardiovascular events but heterogeneous effects on kidney function and BP. Procedure-related adverse events were rare, and medication-related adverse events were not reported. Two RCTs found no patient characteristics that were associated with outcomes with either PTRAS or medical therapy. Single-group studies found various but inconsistent factors that predict outcomes. Case reports provided examples of clinical improvement after PTRAS in patients with acute decompensation. Limitation: Limited clinical applicability and power in RCTs, and possible publication bias and lack of adjusted analyses in NRCSs. Conclusion: The strength of evidence regarding the relative benefits and harms of PTRAS versus medical therapy alone for patients with ARAS is low. Studies have generally focused on patients with less severe ARAS. Primary Funding Source: Agency for Healthcare Research and Quality.

Change in Bone Mineral Density Is an Indicator of Treatment-Related Antifracture Effect in Routine Clinical Practice: A Registry-Based Cohort Study: Annals of Internal Medicine: Vol 165, No 7

Background: Whether change in bone mineral density (BMD) is an accurate indicator of antifracture effect in clinical practice is unknown. Objective: To evaluate repeated BMD testing as an indicator of treatment-related fracture risk reduction. Design: Registry-based cohort study. Setting: Manitoba, Canada. Patients: 6629 women aged 40 years or older initiating osteoporosis treatment with 2 consecutive dual-energy x-ray absorptiometry scans (mean interval, 4.5 years). Measurements: Change in BMD between the first and second dual-energy x-ray absorptiometry scans categorized as stable, detectable decrease, or detectable increase. Incident fractures were ascertained from health services data. Results: During a mean of 9.2 years, 910 (13.7%) women developed incident fractures, including 198 with hip fractures. After adjustment for baseline fracture probability, women with a detectable decrease in total hip BMD compared with stable BMD had an absolute increase of 2.9% (95% CI, 1.5% to 4.4%) and 5.5% (CI, 2.8% to 8.1%) in the 5- and 10-year cumulative incidence of any fracture, respectively. In contrast, risk for any fracture in women with a detectable increase in total hip BMD was 1.3% (CI, 0.4% to 2.2%) and 2.6% (CI, 0.7% to 4.5%) lower after 5 and 10 years, respectively. Consistent results were seen for change in femoral neck and lumbar spine BMD and across a range of subgroup analyses. Limitation: Lack of standardization in the BMD testing interval. Conclusion: Treatment-related increases in total hip BMD are associated with reduced fracture risk compared with stable BMD, whereas decreases in BMD are associated with greater risk for fractures. Monitoring BMD in clinical practice may help to identify women with a suboptimal response to osteoporosis treatment. Primary Funding Source: None.

The Effect of Erythropoietin-Stimulating Agents on Health-Related Quality of Life in Anemia of Chronic Kidney Disease: A Systematic Review and Meta-analysis: Annals of Internal Medicine: Vol 164, No 7

Background: The efficacy of erythropoietin-stimulating agents (ESAs) for improving health-related quality of life (HRQOL) in anemia of chronic kidney disease (CKD) is unclear. Purpose: To determine the effect of ESAs on HRQOL at different hemoglobin targets in adults with CKD who were receiving or not receiving dialysis. Data Sources: Searches of PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov from inception to 1 November 2015, supplemented with manual screening. Study Selection: Randomized, controlled trials that evaluated the treatment of anemia with ESAs, including erythropoietin and darbepoetin, targeted higher versus lower hemoglobin levels, and used validated HRQOL metrics. Data Extraction: Study characteristics, quality, and data were assessed independently by 2 reviewers. Outcome measures were scores on the Short Form-36 Health Survey (SF-36), Kidney Dialysis Questionnaire (KDQ), and other tools. Data Synthesis: Of 17 eligible studies, 13 reported SF-36 outcomes and 4 reported KDQ outcomes. Study populations consisted of patients not undergoing dialysis (n = 12), those undergoing dialysis (n = 4), or a mixed sample (n = 1). Only 4 studies had low risk of bias. Pooled analyses showed that higher hemoglobin targets resulted in no statistically or clinically significant differences in SF-36 or KDQ domains. Differences in HRQOL were further attenuated in studies at low risk of bias and in subgroups of dialysis recipients. Limitation: Statistically significant heterogeneity among studies, few good-quality studies, and possible publication bias. Conclusion: ESA treatment of anemia to obtain higher hemoglobin targets does not result in important differences in HRQOL in patients with CKD. Primary Funding Source: KRESCENT and Manitoba Health Research Council Establishment.

Pharmacologic Treatment of Primary Osteoporosis or Low Bone Mass to Prevent Fractures in Adults: A Living Clinical Guideline From the American College of Physicians (Version 1, Update Alert)

Prevalence and Management of Obesity in U.S. Adults With Type 1 Diabetes

Rosuvastatin Myotoxicity After Starting Canagliflozin Treatment: A Case Report

Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women