Consistency of Laboratory Monitoring During Initiation of Mineralocorticoid Receptor Antagonist Therapy in Patients With Heart Failure

Mineralocorticoid receptor antagonists (MRAs) are a cornerstone of heart failure therapy but have a risk of hyperkalemia. Clinical guidelines recommend close monitoring of renal function and electrolyte levels throughout the course of therapy.¹ No large studies have examined whether laboratory monitoring occurs routinely in community practice.

Using the Centers for Medicare & Medicaid Services Virtual Research Data Center to access claims and summary data for beneficiaries from 10 eastern states who were alive and enrolled in fee-for-service Medicare and in the Medicare Part D prescription drug benefit for the entire 2011 calendar year, we analyzed a cohort with prevalent heart failure who newly initiated MRA therapy. We identified patients with prevalent heart failure using the Chronic Conditions Data Warehouse mid-year indicator; we identified incident MRA use by the presence of a Part D claim for eplerenone or spironolactone between May 1 and September 30, 2011, with no such claims between January 1 and April 30, 2011.²

Outcomes included measurement of serum creatinine and potassium levels before and after MRA initiation, as suggested in guidelines. We defined appropriate testing as a claim for a specific test or laboratory panel including creatinine and potassium within 120 days before initiation, 2 or more measurements during the early postinitiation period (days 1 through 10), and 3 or more measurements during the extended postinitiation period (days 11 through 90).

We counted each hospitalization as 1 test during that period. If the initial MRA prescription fill occurred within 3 days after discharge, we considered the patient to have both in-hospital initiation and 1 test during early postinitiation follow-up.

We summarized laboratory testing using frequencies with percentages. We used multivariable logistic regression to estimate associations between patient characteristics and laboratory monitoring, adjusting for demographic characteristics and comorbid conditions. We used a 2-sided P < .05 to establish statistical significance and report 95% confidence intervals. We used SAS version 9.3 (SAS Institute Inc) for all analyses. The institutional review board of the Duke University Health System approved the study and granted a waiver of consent.

The study population included 10 443 Medicare beneficiaries with heart failure and incident MRA therapy. The mean (SD) age was 78.6 (7.8) years, 4142 patients (39.6%) were men, and 8354 (80%) were white. Chronic kidney disease was present in 4744 patients (45.4%), and 5571 patients (53.3%) were taking an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker. Combined, 756 patients (7.2%) received appropriate testing before and after MRA initiation (Table 1).

After initiation of MRA therapy, 1384 patients (13.3%) and 3122 patients (29.9%) received appropriate testing in early and extended follow-up, respectively. In contrast, 5782 (55.4%) and 2328 (22.3%) received no testing in early or extended follow-up, respectively.

Atrial fibrillation, anemia, chronic kidney disease, chronic obstructive pulmonary disease, hypothyroidism, osteoporosis, and use of diuretics were associated with a greater likelihood of appropriate laboratory testing during all periods (Table 2).

Frequent laboratory monitoring of patients with heart failure following MRA initiation is supported by clinical trial evidence and endorsed in guidelines, but we observed low rates of monitoring in clinical practice.^1,3,4 The landmark trials of MRAs in heart failure showed MRAs significantly reduced mortality and cardiovascular readmission compared with placebo.^3,4 However, an analysis of community practice found similar outcomes among patients treated or not treated with an MRA.⁵ One possible explanation may be less rigorous monitoring outside clinical trial settings, which may increase risks of adverse events associated with MRAs.⁶

Closing the gap between the efficacy and effectiveness of MRAs in heart failure will require clinicians to address this issue. Quality improvement initiatives to improve appropriate laboratory monitoring are needed.

Limitations of our study include the limited population, possible inaccurate claims data, and likely unmeasured confounders. In addition, we only captured data on whether and when laboratory testing occurred but not indications for testing or uncompleted tests.

In conclusion, rates of appropriate laboratory monitoring after MRA initiation were low, and greater attention to appropriate laboratory monitoring is needed.

Corresponding Author: Adrian F. Hernandez, MD, MHS, Duke Clinical Research Institute, PO Box 17969, Durham, NC 27715 (adrian.hernandez@duke.edu).

Author Contributions: Dr Cooper had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Cooper, Hammill, Hernandez.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Cooper.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Hammill, Peterson.

Obtained funding: Hernandez.

Administrative, technical, or material support: Cooper, Maciejewski, Curtis.

Study supervision: Peterson, Hernandez.

Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Peterson reported receiving research grants from Eli Lilly and Janssen; and serving as a consultant for Astra Zeneca, Boehringer Ingelheim, Janssen, and Sanofi. Dr Pitt reported serving as a consultant to Bayer, Pfizer, and Relypsa; owning stock in Relypsa; and having a patent pending regarding site-specific delivery of eplerenone to the myocardium. Dr Maciejewski reported owning stock in Amgen. Dr Curtis reported receiving research support from Boston Scientific, Bristol-Myers Squibb, GE Healthcare, GlaxoSmithKline, Johnson & Johnson, Medtronic, Merck, and Novartis. Dr Hernandez reported receiving research grants from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Merck, and Portola Pharmaceuticals; and serving as a consultant for Amgen, Boston Scientific, Bristol-Myers Squibb, Gilead, Janssen, Novartis, Pleuristem Therapeutics, and Sensible. No other disclosures were reported.

Funding/Support: This project was supported in part by grant U19HS021092 from the Agency for Healthcare Research and Quality. Dr Cooper was supported by grant T32HL069749-11A1 from the National Institutes of Health.

Role of the Funder/Sponsor: The National Institutes of Health and the Agency for Healthcare Research and Quality had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimers: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Agency for Healthcare Research and Quality. Dr Peterson is an associate editor, JAMA, but was not involved in the editorial review of or decision to publish this letter.

Additional Contributions: Damon M. Seils, MA (Duke University, Durham, North Carolina), provided editorial assistance and prepared the manuscript. Mr Seils did not receive compensation for his assistance apart from his employment at the institution where the study was conducted.