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June 12, 2014

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Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers May Decrease Mortality in Patients with Chronic Kidney Disease

Reference: J Am Coll Cardiol 2014 Feb 25;63(7):650 (level 2 [mid-level] evidence)

About the Author

LeuenbergerJohn Leuenberger, DO is a senior resident at UHS Wilson Family Medicine Residency in Johnson City, New York. He will be starting a Neuromuscular Medicine +1 Residency at Eastern Maine Medical Center in July 2014. His interests include Osteopathic Manual Medicine, Medical Acupuncture, and spending time with his family in the outdoors fishing, camping, and skiing. Faculty contribution by Dr. Josh Steinberg, MD.

For more information about the residency program, visit the UHS Wilson Medical Center webpage.

Drs. Leuenberger and Steinberg have declared no financial or other competing interests.

A 70-year-old obese patient with stage 3 chronic kidney disease (CKD) is seen for a routine follow-up visit for hypertension. You are currently successfully managing the hypertension with 40 mg of lisinopril. The patient does not have either congestive heart failure (CHF) or diabetes mellitus (DM), two diseases for which angiotensin-converting enzyme inhibitors (ACEI) or angiotensin-receptor blockers (ARB) are indicated as first line treatment because they have shown beneficial effects on mortality. During the encounter the patient asks, �Will this medication help me live longer�?

A recent large cohort of predominately male US veterans with non-dialysis dependent CKD was identified from the Veterans Administration Outpatient Pharmacy dispensation records. The authors performed an analysis to determine if patients who received an ACEI or ARB had decreased mortality compared to those who did not. There were 141,413 patients: 26,051 in the treated group and 115,362 in the untreated group. The cohort was then narrowed by creating a propensity score-matched group of 40,494 patients (20,247 treated and 20,247 untreated) patients to minimize confounding by indications such as CHF or DM. The untreated group was defined by patients who had not received an ACEI/ARB prior to the study or throughout the duration of the follow-up period. Treated patients were defined as having an ACEI/ARB initiated in previously untreated patients within one year of entering the CKD cohort. Once the drug was initiated, the patient remained in the treated group for intention-to-treat analysis. Various statistical methods were used to adjust for selective discontinuation rates of ACEI/ARB. These methods also took into account the possibility that common adverse effects such as hyperkalemia, hypotension or decrease in kidney function might affect both the prescribing of an ACEI/ARB and the outcomes. The primary outcome examined in this study was the mortality rate in the treated and non-treated groups over the course of the follow-up period.

The median follow-up period was 4.7 years, and the propensity score-matched cohort of treated patients had a mortality rate of 25%, while the untreated cohort had a mortality rate of 32%. Patients who were treated with an ACEI/ARB had an associated 19% reduced all-cause mortality rate in the intention-to-treat analysis (HR: 0.81; 95%CI: 0.78-0.84). Out of the 20,247 patients who entered the treated cohort when ACEI/ARB therapy was initiated only 8.4% received medication during 100% of the follow-up period, 17% received it >90% of the time and 66% received it >50% of the time.

This study attempts to address a previously inadequately answered question about the effect on mortality rates in CKD with the use of ACEI/ARBs. In this cohort, ACEI or ARB use was associated with a 19% relative risk reduction and a 7% absolute risk reduction of all-cause mortality. A previous systematic review of 4 randomized trials found conflicting results in 2 studies for the outcome of all-cause mortality when using ACEIs in this population (Cochrane Database Syst Rev 2011 Oct 5;(10):CD007751). In addition, there was significant statistical heterogeneity for this outcome.

These results were obtained in a treated cohort that was more likely to be black and to have diabetes, hypertension, CHF and cardiovascular disease than the untreated cohort. While observational studies generally are at higher risk of bias than RCTs, the authors of this study have gone to great lengths to avoid bias-by-indication by using extensive statistical analyses. Showing an associated benefit with starting an ACEI/ARB in an ageing and chronically ill population that is expected to have a high mortality rate further strengthens the conclusion. These results may support the use of ACEI/ARB for benefits beyond just renal protection in the management of CKD for those patients who do not have CHF or DM, and may eventually lead to ACEI/ARB as the standard of care for all CKD patients. This study re-emphasizes the need for randomized controlled trials with mortality as an endpoint.

For more information, see Hypertension treatment in patients with chronic kidney disease in DynaMed.

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EBSCO Health Launches Pediatric Clinical Information Mobile App

PEMSoft Now Available For iPhone, iPad, and Android Devices

A mobile app designed specifically for pediatricians, emergency department physicians, physicians-in-training and other medical providers caring for children with acute illnesses and injury, is now available from EBSCO Health, the leading provider of clinical decision support solutions for the healthcare industry.

Designed by pediatricians, emergency physicians and other medical specialists, PEMSoft is a pediatric evidence-based point-of-care medical reference tool for hospitals, emergency departments, clinics, pediatric group practices, transport services, and medical schools. The vast content in PEMSoft addresses the entire spectrum of neonatal, infant, child, adolescent and young adult health. PEMSoft authors adhere to a strict evidence-based editorial policy focused on systematic identification, evaluation and consolidation of practice-changing clinical literature.

The PEMSoft Mobile app includes explicit step-by-step emergency critical care procedures, information about common pediatric signs and symptoms and content covering pediatric injuries and management approaches. More than 3,000 evidence-based pediatric topics and a similar number of medical illustrations, clinical images and videos are also available via the mobile app.

The PEMSoft Mobile App is accessible from both Apple and Android devices.

For more information and technical support, visit the PEMSoft Mobile Access page. To view the official press release, click here.

DynaMed Events

June 18, 2014 / 8am-12:30pm

Senior Deputy Editor Alan Ehrlich, MD, will be presenting Medical Marijuana: An Evidenced-Based Assessment of Efficacy and Harms at the Massachusetts Medical Society (MMS) CME Event and Conference.

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