Annals for Educators - 3 July 2018

Osteoporosis Treatment: Not Easy

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

Comparative Effectiveness of Team-Based Care With and Without a Clinical Decision Support System for Diabetes Management: A Cluster Randomized Trial: Annals of Internal Medicine: Vol 176, No 1

Background: Uncontrolled hyperglycemia, hypercholesterolemia, and hypertension are common in persons with diabetes. Objective: To compare the effectiveness of team-based care with and without a clinical decision support system (CDSS) in controlling glycemia, lipids, and blood pressure (BP) among patients with type 2 diabetes. Design: Cluster randomized trial. (ClinicalTrials.gov: NCT02835287) Setting: 38 community health centers in Xiamen, China. Patients: 11 132 persons aged 50 years or older with uncontrolled diabetes and comorbid conditions, 5475 receiving team-based care with a CDSS and 5657 receiving team-based care alone. Intervention: Team-based care was delivered by primary care physicians, health coaches, and diabetes specialists in all centers. In addition, a computerized CDSS, which generated individualized treatment recommendations based on clinical guidelines, was implemented in 19 centers delivering team-based care with a CDSS. Measurements: Coprimary outcomes were mean reductions in hemoglobin A1c (HbA1c) level, low-density lipoprotein cholesterol (LDL-C) level, and systolic BP over 18 months and the proportion of participants with all 3 risk factors controlled at 18 months. Results: During the 18-month intervention, HbA1c levels, LDL-C levels, and systolic BP significantly decreased by −0.9 percentage point (95% CI, −0.9 to −0.8 percentage point), −0.49 mmol/L (CI, −0.53 to −0.45 mmol/L) (−19.0 mg/dL [CI, −20.4 to −17.5 mg/dL]), and −9.1 mm Hg (CI, −9.9 to −8.3 mm Hg), respectively, in team-based care with a CDSS and by −0.6 percentage point (CI, −0.7 to −0.5 percentage point), −0.32 mmol/L (CI, −0.35 to −0.29 mmol/L) (−12.5 mg/dL [CI, −13.6 to −11.3 mg/dL]), and −7.5 mm Hg (CI, −8.4 to −6.6 mm Hg), respectively, in team-based care alone. Net differences were −0.2 percentage point (CI, −0.3 to −0.1 percentage point) for HbA1c level, −0.17 mmol/L (CI, −0.21 to −0.12 mmol/L) (−6.5 mg/dL [CI, −8.3 to −4.6 mg/dL]) for LDL-C level, and −1.5 mm Hg (CI, −2.8 to −0.3 mm Hg) for systolic BP. The proportion of patients with controlled HbA1c, LDL-C, and systolic BP was 16.9% (CI, 15.7% to 18.2%) in team-based care with a CDSS and 13.0% (CI, 11.7% to 14.3%) in team-based care alone. Limitation: There was no usual care control, and clinical outcome assessors were unblinded; the analysis did not account for multiple comparisons. Conclusion: Compared with team-based care alone, team-based care with a CDSS significantly reduced cardiovascular risk factors in patients with diabetes, but the effect was modest. Primary Funding Source: Xiamen Municipal Health Commission.

Early Rhythm Control Therapy for Atrial Fibrillation in Low-Risk Patients: A Nationwide Propensity Score–Weighted Study: Annals of Internal Medicine: Vol 175, No 10

Background: Rhythm control is associated with lower risk for adverse cardiovascular outcomes compared with usual care among patients recently diagnosed with atrial fibrillation (AF) with a CHA2DS2-VASc score of approximately 2 or greater in EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial). Objective: To investigate whether the results can be generalized to patients with low stroke risk. Design: Population-based cohort study. Setting: Nationwide claims database of the Korean National Health Insurance Service. Participants: 54 216 patients with AF having early rhythm control (antiarrhythmic drugs or ablation) or rate control therapy that was initiated within 1 year of the AF diagnosis. Measurements: The effect of early rhythm control on the primary composite outcome of cardiovascular death, ischemic stroke, hospitalization for heart failure, or myocardial infarction was compared between eligible and ineligible patients for EAST-AFNET 4 (CHA2DS2-VASc score, approximately 0 to 1) using propensity overlap weighting. Results: In total, 37 557 study participants (69.3%) were eligible for the trial (median age, 70 years; median CHA2DS2-VASc score, 4), among whom early rhythm control was associated with lower risk for the primary composite outcome than rate control (hazard ratio, 0.86 [95% CI, 0.81 to 0.92]). Among the 16 659 low-risk patients (30.7%) who did not meet the inclusion criteria (median age, 54 years; median CHA2DS2-VASc score, 1), early rhythm control was consistently associated with lower risk for the primary outcome (hazard ratio, 0.81 [CI, 0.66 to 0.98]). No significant differences in safety outcomes were found between the rhythm and rate control strategies regardless of trial eligibility. Limitation: Residual confounding. Conclusion: In routine clinical practice, the beneficial association between early rhythm control and cardiovascular complications was consistent among low-risk patients regardless of trial eligibility. Primary Funding Source: The Ministry of Health and Welfare and the Ministry of Food and Drug Safety, Republic of Korea.

Cardiovascular Outcomes in Patients Initiating First-Line Treatment of Type 2 Diabetes With Sodium–Glucose Cotransporter-2 Inhibitors Versus Metformin: A Cohort Study: Annals of Internal Medicine: Vol 175, No 7

Background: Evidence on the risk for cardiovascular events associated with use of first-line sodium–glucose cotransporter-2 inhibitors (SGLT-2i) compared with metformin is limited. Objective: To assess cardiovascular outcomes among adults with type 2 diabetes (T2D) who initiated first-line treatment with SGLT-2i versus metformin. Design: Population-based cohort study. Setting: Claims data from 2 large U.S. commercial and Medicare databases (April 2013 to March 2020). Participants: Patients with T2D aged 18 years and older (>65 years in Medicare) initiating treatment with SGLT-2i or metformin during April 2013 to March 2020, without any use of antidiabetic medications before cohort entry, were identified. After 1:2 propensity score matching in each database, pooled hazard ratios (HRs) and 95% CIs were reported. Intervention: First-line SGLT-2i (canagliflozin, empagliflozin, or dapagliflozin) or metformin. Measurements: Primary outcomes were a composite of hospitalization for myocardial infarction (MI), hospitalization for ischemic or hemorrhagic stroke or all-cause mortality (MI/stroke/mortality), and a composite of hospitalization for heart failure (HHF) or all-cause mortality (HHF/mortality). Safety outcomes including genital infections were assessed. Results: Among 8613 first-line SGLT-2i initiators matched to 17 226 metformin initiators, SGLT-2i initiators had a similar risk for MI/stroke/mortality (HR, 0.96; 95% CI, 0.77 to 1.19) and a lower risk for HHF/mortality (HR, 0.80; CI, 0.66 to 0.97) during a mean follow-up of 12 months. Initiators receiving SGLT-2i showed a lower risk for HHF (HR, 0.78; CI, 0.63 to 0.97), a numerically lower risk for MI (HR, 0.70; CI, 0.48 to 1.00), and similar risk for stroke, mortality, and MI/stroke/HHF/mortality compared with metformin. Initiators receiving SGLT-2i had a higher risk for genital infections (HR, 2.19; CI, 1.91 to 2.51) and otherwise similar safety as those receiving metformin. Limitation: Treatment selection was not randomized. Conclusion: As first-line T2D treatment, initiators receiving SGLT-2i showed a similar risk for MI/stroke/mortality, lower risk for HHF/mortality and HHF, and a similar safety profile except for an increased risk for genital infections compared with those receiving metformin. Primary Funding Source: Brigham and Women's Hospital and Harvard Medical School.

Adding a New Medication Versus Maximizing Dose to Intensify Hypertension Treatment in Older Adults: A Retrospective Observational Study: Annals of Internal Medicine: Vol 174, No 12

Background: There are 2 approaches to intensifying antihypertensive treatment when target blood pressure is not reached, adding a new medication and maximizing dose. Which strategy is better is unknown. Objective: To assess the frequency of intensification by adding a new medication versus maximizing dose, as well as the association of each method with intensification sustainability and follow-up systolic blood pressure (SBP). Design: Large-scale, population-based, retrospective cohort study. Observational data were used to emulate a target trial with 2 groups, new medication and maximizing dose, who underwent intensification of their drug regimen. Setting: Veterans Health Administration (2011 to 2013). Patients: Veterans aged 65 years or older with hypertension, an SBP of 130 mm Hg or higher, and at least 1 antihypertensive medication at less than the maximum dose. Measurements: The following 2 intensification approaches were emulated: adding a new medication, defined as a total dose increase with new medication, and maximizing dose, defined as a total dose increase without new medication. Inverse probability weighting was used to assess the observational effectiveness of the intensification approach on sustainability of intensified treatment and follow-up SBP at 3 and 12 months. Results: Among 178 562 patients, 45 575 (25.5%) had intensification by adding a new medication and 132 987 (74.5%) by maximizing dose. Compared with maximizing dose, adding a new medication was associated with less intensification sustainability (average treatment effect, −15.2% [95% CI, −15.7% to −14.6%] at 3 months and −15.1% [CI, −15.6% to −14.5%] at 12 months) but a slightly larger reduction in mean SBP (−0.8 mm Hg [CI, −1.2 to −0.4 mm Hg] at 3 months and −1.1 mm Hg [CI, −1.6 to −0.6 mm Hg] at 12 months). Limitation: Observational data; largely male population. Conclusion: Adding a new antihypertensive medication was less frequent and was associated with less intensification sustainability but slightly larger reductions in SBP. Trials would provide the most definitive support for our findings. Primary Funding Source: National Institute on Aging and Veterans Health Administration.

Management of Dyslipidemia for Cardiovascular Disease Risk Reduction: Synopsis of the 2020 Updated U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline

Description: In June 2020, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) released a joint update of their clinical practice guideline for managing dyslipidemia to reduce cardiovascular disease risk in adults. This synopsis describes the major recommendations. Methods: On 6 August to 9 August 2019, the VA/DoD Evidence-Based Practice Work Group (EBPWG) convened a joint VA/DoD guideline development effort that included clinical stakeholders and conformed to the Institute of Medicine's tenets for trustworthy clinical practice guidelines. The guideline panel developed key questions, systematically searched and evaluated the literature (English-language publications from 1 December 2013 to 16 May 2019), and developed 27 recommendations and a simple 1-page algorithm. The recommendations were graded by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Recommendations: This synopsis summarizes key features of the guideline in 7 crucial areas: targeting of statin dose (not low-density lipoprotein cholesterol goals), additional tests for risk prediction, primary and secondary prevention, laboratory testing, physical activity, and nutrition.

Mental Health Treatment for Front-Line Clinicians During and After the Coronavirus Disease 2019 (COVID-19) Pandemic: A Plea to the Medical Community

Should Clinicians Use Chloroquine or Hydroxychloroquine Alone or in Combination With Azithromycin for the Prophylaxis or Treatment of COVID-19? Living Practice Points From the American College of Physicians (Version 1)