Management of Blood Pressure in Patients With Chronic Kidney Disease Not Receiving Dialysis: Synopsis of the 2021 KDIGO Clinical Practice Guideline

Description: The Kidney Disease: Improving Global Outcomes (KDIGO) 2021 clinical practice guideline for the management of blood pressure (BP) in patients with chronic kidney disease (CKD) not receiving dialysis is an update of the KDIGO 2012 guideline on the same topic and reflects new evidence on the risks and benefits of BP-lowering therapy among patients with CKD. It is intended to support shared decision making by health care professionals working with patients with CKD worldwide. This article is a synopsis of the full guideline. Methods: The KDIGO leadership commissioned 2 co-chairs to convene an international Work Group of researchers and clinicians. After a Controversies Conference in September 2017, the Work Group defined the scope of the evidence review, which was undertaken by an evidence review team between October 2017 and April 2020. Evidence reviews were done according to the Cochrane Handbook. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used to guide the development of the recommendations and rate the strength and quality of the evidence. Practice points were included to provide guidance when evidence was insufficient to make a graded recommendation. The guideline was revised after public consultation between January and March 2020. Recommendations: The updated guideline comprises 11 recommendations and 20 practice points. This synopsis summarizes key recommendations pertinent to the diagnosis and management of high BP in adults with CKD, excluding those receiving kidney replacement therapy. In particular, the synopsis focuses on recommendations for standardized BP measurement and a target systolic BP of less than 120 mm Hg, because these recommendations differ from some other guidelines.

Annual Tuberculosis Preventive Therapy for Persons With HIV Infection: A Randomized Trial: Annals of Internal Medicine: Vol 174, No 10

Background: Tuberculosis preventive therapy for persons with HIV infection is effective, but its durability is uncertain. Objective: To compare treatment completion rates of weekly isoniazid–rifapentine for 3 months versus daily isoniazid for 6 months as well as the effectiveness of the 3-month rifapentine–isoniazid regimen given annually for 2 years versus once. Design: Randomized trial. (ClinicalTrials.gov: NCT02980016) Setting: South Africa, Ethiopia, and Mozambique. Participants: Persons with HIV infection who were receiving antiretroviral therapy, were aged 2 years or older, and did not have active tuberculosis. Intervention: Participants were randomly assigned to receive weekly rifapentine–isoniazid for 3 months, given either annually for 2 years or once, or daily isoniazid for 6 months. Participants were screened for tuberculosis symptoms at months 0 to 3 and 12 of each study year and at months 12 and 24 using chest radiography and sputum culture. Measurements: Treatment completion was assessed using pill counts. Tuberculosis incidence was measured over 24 months. Results: Between November 2016 and November 2017, 4027 participants were enrolled; 4014 were included in the analyses (median age, 41 years; 69.5% women; all using antiretroviral therapy). Treatment completion in the first year for the combined rifapentine–isoniazid groups (n = 3610) was 90.4% versus 50.5% for the isoniazid group (n = 404) (risk ratio, 1.78 [95% CI, 1.61 to 1.95]). Tuberculosis incidence among participants receiving the rifapentine–isoniazid regimen twice (n = 1808) or once (n = 1802) was similar (hazard ratio, 0.96 [CI, 0.61 to 1.50]). Limitation: If rifapentine–isoniazid is effective in curing subclinical tuberculosis, then the intensive tuberculosis screening at month 12 may have reduced its effectiveness. Conclusion: Treatment completion was higher with rifapentine–isoniazid for 3 months compared with isoniazid for 6 months. In settings with high tuberculosis transmission, a second round of preventive therapy did not provide additional benefit to persons receiving antiretroviral therapy. Primary Funding Source: The U.S. Agency for International Development through the CHALLENGE TB grant to the KNCV Tuberculosis Foundation.

The Safety and Immunologic Effectiveness of the Live Varicella-Zoster Vaccine in Patients Receiving Tumor Necrosis Factor Inhibitor Therapy: A Randomized Controlled Trial: Annals of Internal Medicine: Vol 174, No 11

Background: The safety and effectiveness of live virus vaccines, such as the varicella-zoster vaccine, are unknown in patients with inflammatory diseases receiving immunomodulatory therapy such as tumor necrosis factor inhibitors (TNFis). Objective: To evaluate the safety and immunogenicity of the live attenuated zoster vaccine (ZVL) in patients receiving TNFis. Design: Randomized, blinded, placebo-controlled trial. (ClinicalTrials.gov: NCT02538341) Setting: Academic and community-based rheumatology, gastroenterology, and dermatology practices. Patients: Adults aged 50 years or older receiving TNFis for any indication. Intervention: Random assignment to ZVL versus placebo. Measurements: Glycoprotein enzyme-linked immunosorbent assay (gpELISA) and enzyme-linked immunosorbent spot (ELISpot) from serum and peripheral blood mononuclear cells measured at baseline and 6 weeks after vaccination. Suspected varicella infection or herpes zoster was clinically assessed using digital photographs and polymerase chain reaction on vesicular fluid. Results: Between March 2015 and December 2018, 617 participants were randomly assigned in a 1:1 ratio to receive ZVL (n = 310) or placebo (n = 307) at 33 centers. Mean age was 62.7 years (SD, 7.5); 66.1% of participants were female, 90% were White, 8.2% were Black, and 5.9% were Hispanic. The most common TNFi indications were rheumatoid arthritis (57.6%) and psoriatic arthritis (24.1%); TNFi medications were adalimumab (32.7%), infliximab (31.3%), etanercept (21.2%), golimumab (9.1%), and certolizumab (5.7%). Concomitant therapies included methotrexate (48.0%) and oral glucocorticoids (10.5%). Through week 6, no cases of confirmed varicella infection were found; cumulative incidence of varicella infection or shingles was 0.0% (95% CI, 0.0% to 1.2%). At 6 weeks, compared with baseline, the mean increases in geometric mean fold rise as measured by gpELISA and ELISpot were 1.33 percentage points (CI, 1.17 to 1.51 percentage points) and 1.39 percentage points (CI, 1.07 to 1.82 percentage points), respectively. Limitation: Potentially limited generalizability to patients receiving other types of immunomodulators. Conclusion: This trial informs safety concerns related to use of live virus vaccines in patients receiving biologics. Primary Funding Source: The National Institute of Arthritis and Musculoskeletal and Skin Diseases and the American College of Rheumatology.

Diabetes Management in Chronic Kidney Disease: Synopsis of the 2020 KDIGO Clinical Practice Guideline

Description: The Kidney Disease: Improving Global Outcomes (KDIGO) organization developed a clinical practice guideline in 2020 for the management of patients with diabetes and chronic kidney disease (CKD). Methods: The KDIGO Work Group (WG) was tasked with developing the guideline for diabetes management in CKD. It defined the scope of the guideline, gathered evidence, determined systematic review topics, and graded evidence that had been summarized by an evidence review team. The English-language literature searches, which were initially done through October 2018, were updated in February 2020. The WG used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of the recommendations. Expert judgment was used to develop consensus practice points supplementary to the evidence-based graded recommendations. The guideline document underwent open public review. Comments from various stakeholders, subject matter experts, and industry and national organizations were considered before the document was finalized. Recommendations: The guideline includes 12 recommendations and 48 practice points for clinicians caring for patients with diabetes and CKD. This synopsis focuses on the key recommendations pertinent to the following issues: comprehensive care needs, glycemic monitoring and targets, lifestyle interventions, antihyperglycemic therapies, and educational and integrated care approaches.

Effects of Intensive Blood Pressure Treatment on Orthostatic Hypotension: A Systematic Review and Individual Participant–based Meta-analysis: Annals of Internal Medicine: Vol 174, No 1

Background: Although intensive blood pressure (BP)–lowering treatment reduces risk for cardiovascular disease, there are concerns that it might cause orthostatic hypotension (OH). Purpose: To examine the effects of intensive BP-lowering treatment on OH in hypertensive adults. Data Sources: MEDLINE, EMBASE, and Cochrane CENTRAL from inception through 7 October 2019, without language restrictions. Study Selection: Randomized trials of BP pharmacologic treatment (more intensive BP goal or active agent) that involved more than 500 adults with hypertension or elevated BP and that were 6 months or longer in duration. Trial comparisons were groups assigned to either less intensive BP goals or placebo, and the outcome was measured OH, defined as a decrease of 20 mm Hg or more in systolic BP or 10 mm Hg or more in diastolic BP after changing position from seated to standing. Data Extraction: 2 investigators independently abstracted articles and rated risk of bias. Data Synthesis: 5 trials examined BP treatment goals, and 4 examined active agents versus placebo. Trials examining BP treatment goals included 18 466 participants with 127 882 follow-up visits. Trials were open-label, with minimal heterogeneity of effects across trials. Intensive BP treatment lowered risk for OH (odds ratio, 0.93 [95% CI, 0.86 to 0.99]). Effects did not differ by prerandomization OH (P for interaction = 0.80). In sensitivity analyses that included 4 additional placebo-controlled trials, overall and subgroup findings were unchanged. Limitations: Assessments of OH were done while participants were seated (not supine) and did not include the first minute after standing. Data on falls and syncope were not available. Conclusion: Intensive BP-lowering treatment decreases risk for OH. Orthostatic hypotension, before or in the setting of more intensive BP treatment, should not be viewed as a reason to avoid or de-escalate treatment for hypertension. Primary Funding Source: National Heart, Lung, and Blood Institute, National Institutes of Health. (PROSPERO: CRD42020153753)

Pharmacologic Approaches to Glycemic Treatment of Type 2 Diabetes: Synopsis of the 2020 American Diabetes Association's Standards of Medical Care in Diabetes Clinical Guideline

Description: The American Diabetes Association (ADA) updates the Standards of Medical Care in Diabetes annually to provide clinicians, patients, researchers, payers, and other interested parties with evidence-based recommendations for the diagnosis and management of diabetes. Methods: To develop the 2020 Standards, the ADA Professional Practice Committee, comprising physicians, adult and pediatric endocrinologists, diabetes educators, registered dietitians, epidemiologists, pharmacists, and public health experts, continuously searched MEDLINE (English language only) from 15 October 2018 through August–September 2019 for pertinent studies, including high-quality trials that addressed pharmacologic management of type 2 diabetes. The committee selected and reviewed the studies, developed the recommendations, and solicited feedback from the larger clinical community. Recommendations: This synopsis focuses on guidance relating to the pharmacologic treatment of adults with type 2 diabetes. Recommendations address oral and noninsulin injectable therapies, insulin treatment, and combination injectable therapies. Results of recent large trials with cardiovascular and renal outcomes are emphasized.

World Health Organization Guidelines on Treatment of Hepatitis C Virus Infection: Best Practice Advice From the American College of Physicians

Association Between Treatment With Apixaban, Dabigatran, Rivaroxaban, or Warfarin and Risk for Osteoporotic Fractures Among Patients With Atrial Fibrillation: A Population-Based Cohort Study: Annals of Internal Medicine: Vol 173, No 1

Background: It is unclear whether anticoagulant type is associated with the risk for osteoporotic fracture, a deleterious complication of anticoagulants among patients with atrial fibrillation (AF). Objective: To compare the risk for osteoporotic fracture between anticoagulants. Design: Population-based cohort study. Setting: Territory-wide electronic health record database of the Hong Kong Hospital Authority. Participants: Patients newly diagnosed with AF between 2010 and 2017 who received a new prescription for warfarin or a direct oral anticoagulant (DOAC) (apixaban, dabigatran, or rivaroxaban). Follow-up ended on 31 December 2018. Measurements: Osteoporotic hip and vertebral fractures in anticoagulant users were compared using propensity score–weighted cumulative incidence differences (CIDs). Results: There were 23 515 patients identified (3241 apixaban users, 6867 dabigatran users, 3866 rivaroxaban users, and 9541 warfarin users). Overall mean age was 74.4 years (SD, 10.8), ranging from 73.1 years (warfarin) to 77.9 years (apixaban). Over a median follow-up of 423 days, 401 fractures were identified (crude event number [weighted rate per 100 patient-years]: apixaban, 53 [0.82]; dabigatran, 95 [0.76]; rivaroxaban, 57 [0.67]; and warfarin, 196 [1.11]). After 24-month follow-up, DOAC use was associated with a lower risk for fracture than warfarin use (apixaban CID, −0.88% [95% CI, −1.66% to −0.21%]; dabigatran CID, −0.81% [CI, −1.34% to −0.23%]; and rivaroxaban CID, −1.13% [CI, −1.67% to −0.53%]). No differences were seen in all head-to-head comparisons between DOACs at 24 months (apixaban vs. dabigatran CID, −0.06% [CI, −0.69% to 0.49%]; rivaroxaban vs. dabigatran CID, −0.32% [CI, −0.84% to 0.18%]; and rivaroxaban vs. apixaban CID, −0.25% [CI, −0.86% to 0.40%]). Limitation: Residual confounding is possible. Conclusion: Among patients with AF, DOAC use may result in a lower risk for osteoporotic fracture compared with warfarin use. Fracture risk does not seem to be altered by the choice of DOAC. These findings may help inform the benefit–risk assessment when choosing between anticoagulants. Primary Funding Source: The University of Hong Kong and University College London Strategic Partnership Fund.

Pharmacologic Therapies in Patients With Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review With Meta-analysis: Annals of Internal Medicine: Vol 172, No 6

Background: Chronic obstructive pulmonary disease (COPD) is characterized by frequent exacerbations. Purpose: To evaluate the comparative effectiveness and adverse events (AEs) of pharmacologic interventions for adults with exacerbation of COPD. Data Sources: English-language searches of several bibliographic sources from database inception to 2 January 2019. Study Selection: 68 randomized controlled trials that enrolled adults with exacerbation of COPD treated in out- or inpatient settings other than intensive care and compared pharmacologic therapies with placebo, “usual care,” or other pharmacologic interventions. Data Extraction: Two reviewers independently extracted data and rated study quality and strength of evidence (SOE). Data Synthesis: Compared with placebo or management without antibiotics, antibiotics given for 3 to 14 days were associated with increased exacerbation resolution at the end of the intervention (odds ratio [OR], 2.03 [95% CI, 1.47 to 2.80]; moderate SOE) and less treatment failure at the end of the intervention (OR, 0.54 [CI, 0.34 to 0.86]; moderate SOE), independent of severity of exacerbations in out- and inpatients. Compared with placebo in out- and inpatients, systemic corticosteroids given for 9 to 56 days were associated with less treatment failure at the end of the intervention (OR, 0.01 [CI, 0.00 to 0.13]; low SOE) but also with a higher number of total and endocrine-related AEs. Compared with placebo or usual care in inpatients, other pharmacologic interventions (aminophyllines, magnesium sulfate, anti-inflammatory agents, inhaled corticosteroids, and short-acting bronchodilators) had insufficient evidence, showing either no or inconclusive effects (with the exception of the mucolytic erdosteine) or improvement only in lung function. Limitation: Scant evidence for many interventions; several studies had unclear or high risk of bias and inadequate reporting of AEs. Conclusion: Antibiotics and systemic corticosteroids reduce treatment failure in adults with mild to severe exacerbation of COPD. Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018111609)

Should Health Care Demand Interpretable Artificial Intelligence or Accept “Black Box” Medicine?