Clinical InvestigationsOutcomes in patients with cardiometabolic disease who develop hyperkalemia while treated with a renin-angiotensin-aldosterone system inhibitor
Section snippets
Study design
We performed a retrospective cohort study to assess the relationship of hyperkalemia with treatment and outcomes of patients being treated with RAASi.
Participants
Study participants included adults (≥18 years old) who were treated with a RAASi and received their primary care from a provider affiliated with Mass General Brigham. Patients were required to have a baseline creatinine level available and at least one of the following indications for RAASi therapy: (a) diabetes mellitus (DM) and proteinuria; (b)
Sources of funding
This study was funded in part by Astra-Zeneca. The study funder contributed to the study design and manuscript review. The study funder had no role in conduct of the study; collection, management, analysis, and interpretation of the data; and decision to submit the manuscript for publication.
Results
We identified 94,280 adult patients who had indications for RAASi therapy and were treated with a RAASi. After excluding patients with history of angioedema, advanced CKD or were missing demographic or baseline potassium information (Figure 1), 82,732 patients were included in analysis (Table 1). Of these, 24,467 (29.6%) patients had DM and proteinuria; 7,224 (8.7%) had heart failure with LVEF ≤ 40%; 44,737 (54.1%) had CAD; and 39,073 (27.2%) CKD stage I-IV and proteinuria (some patients had
Discussion
In this large population-based study of patients treated with RAASi for evidence-based indications, we found that hyperkalemia was common and was associated with an increased risk of adverse outcomes. Many patients who developed hyperkalemia had their RAASi deintensified (stopped or dose decreased); RAASi deintensification was linked to a higher risk of adverse outcomes.
The present study showed that hyperkalemia was linked to an increased risk to a broad range of adverse outcomes, including
Conclusions
In conclusion, the present study found that patients treated with RAASi commonly develop hyperkalemia. Deintensification of RAASi therapy remains a widespread approach to prevention of hyperkalemia recurrence in this patient population and is associated with a significantly increased risk of adverse clinical outcomes. Broad implementation of safe and effective treatments for prevention of hyperkalemia that would enable continuation of RAASi therapy could make a significant impact on quality of
Conflict of Interest
Dr McMahon has received personal fees from Apellis and grant support from Alexion and Allena. Dr Turchin has equity in Brio Systems; has received personal fees from Covance and Proteomics International; and received grant support from Eli Lilly, Edwards, and Novo Nordisk. None of the other authors have any conflicts of interest.
References (55)
- et al.
Antihypertensive therapy in the presence of proteinuria
Am J Kidney Dis
(2007) - et al.
Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. ACE-Inhibitor Myocardial Infarction Collaborative Group
Lancet
(2000) - et al.
Long-term renoprotective effects of standard versus high doses of telmisartan in hypertensive nondiabetic nephropathies
Am J Kidney Dis
(2005) - et al.
Outpatient utilization of angiotensin-converting enzyme inhibitors among heart failure patients after hospital discharge
J Am Coll Cardiol
(2004) - et al.
Contemporary epidemiology, management, and outcomes of patients hospitalized for heart failure in China: results from the China heart failure (China-HF) registry
J Cardiac Fail
(2017) - et al.
Underuse of ACE inhibitors and angiotensin II receptor blockers in elderly patients with diabetes
Am J Kidney Dis
(2005) - et al.
Titration of medical therapy for heart failure with reduced ejection fraction
J Am Coll Cardiol
(2019) - et al.
Enhanced renoprotective effects of ultrahigh doses of irbesartan in patients with type 2 diabetes and microalbuminuria
Kidney Int
(2005) - et al.
Spironolactone-induced renal insufficiency and hyperkalemia in patients with heart failure
Am Heart J
(2004) - et al.
A new method of classifying prognostic comorbidity in longitudinal studies: development and validation
J Chronic Dis
(1987)