Outlines of K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease

Recently "K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease" was published. It consists of sixteen precise guidelines which cover the wide range of this field. It is expected that these guidelines contribute ESRD treatment in Japan in spite of some differences in medical practice for dialysis therapy between Japan and the United States. This article briefly summarizes the outlines of these guidelines.     

Problems in adapting the K/DOQI guidelines for Japanese patients with end stage renal failure

The National Kidney Foundation published The K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease. We should also consider differences in clinical features of management for renal osteodystrophy between Japan and the USA. The first problem is related to a difference in the method of Ca correction. The second problem is related to a difference in the timing of measurement. In the USA the timing of measurement varies with each institution. Briefly, it is performed at midweek (2 days after the last dialysis) in some of institutions, while at the beginning of next week (3 days after the last dialysis) in some others. In addition, differences in the dose and type of the calcium-containing phosphorus adsorbent and active vitamin D used should also be taken into consideration.     

Inconsistencies in the development of the ESC Clinical Practice Guidelines for Heart Failure

The publication of the European Society of Cardiology (ESC) guidelines for the management of heart failure, in 2012 represented the latest and arguably the most comprehensive document to date summarising recommended treatment and diagnostic options for the care of heart failure patients. The impact of clinical practice guidelines is now so great that it is important to review the processes that underlie guideline development. The ESC guideline process is compared and contrasted to those of other guideline bodies. The ESC uses its own internal experts inclined to review source clinical trial data rather than published or commissioned meta-analyses and systematic reviews. Uncertainties exist in several areas, such as how are the scope of potential treatments to be reviewed chosen, if there is no call for proposals or external consultation?, Two illustrative discrepancies are highlighted i) the non-surgical MitraClip device for reducing mitral regurgitation is given the verbal equivalent of a Class IIb recommendation on the basis of 107 patients in an uncontrolled registry, whereas no drug is reviewed based on such data, and another device, the subject of 3 prospective randomised controlled trials, was not reviewed at all and ii) for Ivabradine the whole trial population was included in the recommendation, despite a subgroup not benefitting, whereas for CRT the sub-group not thought to benefit was excluded from the recommendation. We propose that more interaction is needed between ESC and stakeholders so each can better understand the processes for producing guidelines to improve some of these aspects.     

Efficacy of percutaneous ethanol injection therapy for secondary hyperparathyroidism in patients on hemodialysis as evaluated by parathyroid hormone levels according to K/DOQI guidelines

Secondary hyperparathyroidism (SHPT) is a major complication of hemodialysis patients. Recently, percutaneous ethanol injection therapy (PEIT) has become a useful alternative treatment to parathyroidectomy (PTx). In this study, we evaluate the usefulness of PEIT for SHPT according to Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. We studied 28 patients on hemodialysis with high intact-PTH (>400 pg/mL) and one to four swollen parathyroid glands detected by power Doppler ultrasonography. They were classified into Group 1 (N = 16), with 1 or 2 swollen glands, Group 2 (N = 5), with 3 or 4 swollen glands, and Group 3 (N = 7), high-risk patients for PTx. We compared serum intact-PTH levels 1 year after PEIT according to K/DOQI guidelines among these groups. We also evaluated the effectiveness of PEIT and PTx by comparing intact-PTH levels in 21 patients 1 year after PEIT (groups 1 and 2) with 11 patients after PTx. In Group 1, adequate intact-PTH levels were noted in 13 of 16 (81.2%) patients after PEIT, while 1 patient of 5 (20%) was achieved in Group 2, and 2 of 7 (28.6%) patients of Group 3. Adequate intact-PTH levels were attained in 14 of 21 (66.7%) patients of the PEIT group but only in 2 of 11 (18.2%) patients of the PTx group. Our results suggest that PEIT is a useful treatment for SHPT, especially in patients with one or two swollen glands. Through appropriate selection of patients for PEIT and correct injection of ethanol into the enlarged parathyroid gland, PEIT could accomplish better outcomes based on K/DOQI guidelines.     

Interventional Therapy Versus Medical Therapy for Secundum Atrial Septal Defect: A Systematic Review (Part 2) for the 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines

Secundum atrial septal defect (ASD) is the most common adult congenital heart defect and can present with wide variation in clinical findings. With the intention of preventing morbidity and mortality associated with late presentation of ASD, consensus guidelines have recommended surgical or percutaneous ASD closure in adults with right heart enlargement, with or without symptoms. The aim of the present analysis was to determine if the protective effect of secundum ASD closure in adults could be qualified by pooling data from published studies.A systematic review and meta-analysis were performed by using EMBASE, MEDLINE (through PubMed), and the Cochrane Library databases to assess the effect of secundum ASD percutaneous or surgical closure in unoperated adults ≥18 years of age. Data were pooled across studies with the DerSimonian-Laird random-effects model or a Bayesian meta-analysis model. Between-study heterogeneity was assessed with Cochran’s Q test. Bias assessment was performed with the Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool, and statistical risk of bias was assessed with Begg and Mazumdar’s test and Egger’s test.A total of 11 nonrandomized studies met the inclusion criteria, contributing 603 patients. Pooled analysis showed a protective effect of ASD closure on New York Heart Association functional class and on right ventricular systolic pressure, volumes, and dimensions. Two additional studies comprising 652 patients were reviewed separately for mortality outcome and primary outcome of interest because they did not meet the inclusion criteria. Those studies showed that ASD closure was associated with a weak protective effect on adjusted mortality rate but no significant impact on atrial arrhythmias in patients >50 years of age. Across all studies, there was significant heterogeneity between studies for nearly all clinical outcomes. The overall body of evidence was limited to observational cohort studies, the limitations of which make for low-strength evidence. Even within the parameters of the included studies, quality of evidence was further diminished by the lack of well-defined clinical outcomes.In conclusion, pooled data analysis on the impact of secundum ASD closure in adults was notably limited because of the lack of randomized controlled trials in patients with only secundum ASD. The few cohort studies in this population demonstrated improvement in functional status and right ventricular size and function as shown by echocardiogram. However, our findings suggest that at the time of this publication, insufficient data are available to determine the impact of ASD repair on mortality rate in adults.     

Systematic Review for the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines

BackgroundThe 2013 American College of Cardiology/American Heart Association guidelines for the treatment of blood cholesterol found little evidence to support the use of nonstatin lipid-modifying medications to reduce atherosclerotic cardiovascular disease (ASCVD) events. Since publication of these guidelines, multiple randomized controlled trials evaluating nonstatin lipid-modifying medications have been published.MethodsWe performed a systematic review to assess the magnitude of benefit and/or harm from additional lipid-modifying therapies compared with statins alone in individuals with known ASCVD or at high risk of ASCVD. We included data from randomized controlled trials with a sample size of >1,000 patients and designed for follow-up >1 year. We performed a comprehensive literature search and identified 10 randomized controlled trials for intensive review, including trials evaluating ezetimibe, niacin, cholesterol-ester transfer protein inhibitors, and PCSK9 inhibitors. The prespecified primary outcome for this review was a composite of fatal cardiovascular events, nonfatal myocardial infarction, and nonfatal stroke.ResultsThe cardiovascular benefit of nonstatin lipid-modifying therapies varied significantly according to the class of medication. There was evidence for reduced ASCVD morbidity with ezetimibe and 2 PSCK9 inhibitors. Reduced ASCVD mortality rate was reported for 1 PCSK9 inhibitor. The use of ezetimibe/simvastatin versus simvastatin in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) reduced the primary outcome by 1.8% over 7 years (hazard ratio: 0.90; 95% CI: 0.84–0.96], 7-year number needed to treat: 56). The PSCK9 inhibitor evolocumab in the FOURIER study (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) decreased the primary outcome by 1.5% over 2.2 years (hazard ratio: 0.80; 95% CI: 0.73–0.88; 2.2=year number needed to treat: 67). In ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), alirocumab reduced the primary outcome by 1.6% over 2.8 years (hazard ratio: 0.86; 95% CI: 0.79–0.93; 2.8-year number needed to treat: 63). For ezetimibe and the PSCK9 inhibitors, rates of musculoskeletal, neurocognitive, gastrointestinal, or other adverse event risks did not differ between the treatment and control groups. For patients at high risk of ASCVD already on background statin therapy, there was minimal evidence for improved ASCVD risk or adverse events with cholesterol-ester transfer protein inhibitors. There was no evidence of benefit for the addition of niacin to statin therapy. Direct comparisons of the results of the 10 randomized controlled trials were limited by significant differences in sample size, duration of follow-up, and reported primary outcomes.ConclusionsIn a systematic review of the evidence for adding nonstatin lipid-modifying therapies to statins to reduce ASCVD risk, we found evidence of benefit for ezetimibe and PCSK9 inhibitors but not for niacin or cholesterol-ester transfer protein inhibitors.