Rates of Hyperkalemia after Publication of the Randomized Aldactone Evaluation Study

Juurlink, David N.; Mamdani, Muhammad; Lee, Douglas S.; Kopp, Alexander; Austin, Peter C.; Laupacis, Andreas; Redelmeier, Donald A.

doi:10.1056/nejmoa040135

Cited by 1,537 publications

(870 citation statements)

References 25 publications

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“…Risks of hyperkalemia and worsening renal function often limit use of MRA therapy in patients with heart failure 12, 13, 14. Several factors increase hyperkalemia risk, including renal insufficiency and diabetes mellitus 15, 16, 17, 18, 19.…”

Section: Introductionmentioning

confidence: 99%

Use of Mineralocorticoid Receptor Antagonists in Patients With Heart Failure and Comorbid Diabetes Mellitus or Chronic Kidney Disease

Cooper

Lippmann

Greiner

et al. 2017

JAHA

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BackgroundPerceived risks of hyperkalemia and acute renal insufficiency may limit use of mineralocorticoid receptor antagonist (MRA) therapy in patients with heart failure, especially those with diabetes mellitus or chronic kidney disease.Methods and ResultsUsing clinical registry data linked to Medicare claims, we analyzed patients hospitalized with heart failure between 2005 and 2013 with a history of diabetes mellitus or chronic kidney disease. We stratified patients by MRA use at discharge. We used inverse probability–weighted proportional hazards models to assess associations between MRA therapy and 30‐day, 1‐year, and 3‐year mortality, all‐cause readmission, and readmission for heart failure, hyperkalemia, and acute renal insufficiency. We performed interaction analyses for differential effects on 3‐year outcomes for reduced, borderline, and preserved ejection fraction. Of 16 848 patients, 12.3% received MRA therapy at discharge. Higher serum creatinine was associated with lower odds of MRA use (odds ratio, 0.66; 95% confidence interval, 0.61–0.71); serum potassium was not (odds ratio, 1.00; 95% confidence interval, 0.90–1.11). There was no mortality difference between groups. MRA therapy was associated with greater risks of readmission for hyperkalemia and acute renal insufficiency and lower risks of long‐term all‐cause readmission. Patients on MRA therapy with borderline or preserved ejection fraction had greater risks of readmission for hyperkalemia (P=0.02) and acute renal insufficiency (P<0.001); patients with reduced ejection fraction did not.ConclusionsAmong patients with heart failure and diabetes mellitus or chronic kidney disease, MRA use was associated with lower risk of all‐cause readmission despite greater risk of hyperkalemia and acute renal insufficiency.

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Section: Introductionmentioning

confidence: 99%

Use of Mineralocorticoid Receptor Antagonists in Patients With Heart Failure and Comorbid Diabetes Mellitus or Chronic Kidney Disease

Cooper

Lippmann

Greiner

et al. 2017

JAHA

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“…Indeed, an increase of in‐hospital death among HF patients was described also by Juurlink's group in a Canadian population study. In that population, the publication of RALES was associated with an increase in spironolactone use and in the rates of hospital admission for HK and subsequent in‐hospital death among HF patients 10. Similarly, another population study showed that spironolactone use was not associated with improved long‐term survival in the general HF population 15.…”

Section: Discussionmentioning

confidence: 97%

Mineralocorticoid receptor antagonists for heart failure: a real‐life observational study

et al. 2018

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AimsMineralocorticoid receptor antagonists (MRAs) have been demonstrated to improve outcomes in reduced ejection fraction heart failure (HFrEF) patients. However, MRAs added to conventional treatment may lead to worsening of renal function and hyperkalaemia. We investigated, in a population‐based analysis, the long‐term effects of MRA treatment in HFrEF patients.Methods and resultsWe analysed data of 6046 patients included in the Metabolic Exercise Cardiac Kidney Index score dataset. Analysis was performed in patients treated (n = 3163) and not treated (n = 2883) with MRA. The study endpoint was a composite of cardiovascular death, urgent heart transplantation, or left ventricular assist device implantation. Ten years' survival was analysed through Kaplan–Meier, compared by log‐rank test and propensity score matching.At 10 years' follow‐up, the MRA‐untreated group had a significantly lower number of events than the MRA‐treated group (P < 0.001). MRA‐treated patients had more severe heart failure (higher New York Heart Association class and lower left ventricular ejection fraction, kidney function, and peak VO2). At a propensity‐score‐matching analysis performed on 1587 patients, MRA‐treated and MRA‐untreated patients showed similar study endpoint values.ConclusionsIn conclusion, MRA treatment does not affect the composite of cardiovascular death, urgent heart transplantation or left ventricular assist device implantation in a real‐life setting. A meticulous patient follow‐up, as performed in trials, is likely needed to match the positive MRA‐related benefits observed in clinical trials.

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“…Demographic and mortality data were obtained from the Ontario Health Insurance Plan Registered Persons Database, a registry of all Ontario residents with publically‐funded health insurance, and physicians’ services were identified using OHIP physician claims data. These databases were linked in an anonymous fashion using encrypted Ontario health card numbers, and are routinely used to study drug safety 27, 28, 29, 30, 31, 32.…”

Section: Methodsmentioning

confidence: 99%

A population‐based study of the drug interaction between clopidogrel and angiotensin converting enzyme inhibitors

Cressman

Macdonald

Fernandes

et al. 2015

Brit J Clinical Pharma

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AimsClopidogrel and angiotensin converting enzyme (ACE) inhibitors are commonly co‐prescribed drugs. Clopidogrel inhibits carboxylesterase 1 (CES1), the enzyme responsible for converting prodrug ACE inhibitors (such as ramipril and perindopril) to their active metabolites. The clinical implications of this potential drug interaction are unknown. The clinical consequences of the potential drug interaction between clopidogrel and prodrug ACE inhibitors were examined.MethodsWe conducted a nested case–control study of Ontarians aged 66 years and older treated with clopidogrel between September 1 2003 and March 31 2013 following acute myocardial infarction. Cases were subjects who died or were hospitalized for reinfarction or heart failure in the subsequent year, and each was matched with up to four controls. The primary outcome was a composite of reinfarction, heart failure or death. The primary analysis examined whether use of the prodrug ACE inhibitors ramipril or perindopril was more common among cases than use of lisinopril, an active ACE inhibitor.ResultsAmong 45 918 patients treated with clopidogrel following myocardial infarction, we identified 4203 cases and 14 964 controls. After adjustment, we found no association between the composite outcome and use of perindopril (adjusted odds ratio (aOR) 0.94, 95% confidence interval (CI) 0.76, 1.16) or ramipril (aOR 0.97, 95% CI 0.80, 1.18), relative to lisinopril. Secondary analyses of each element of the composite outcome yielded similar findings.ConclusionsFollowing myocardial infarction, use of clopidogrel with ACE inhibitors activated by CES1 is not associated with an increased risk of adverse cardiovascular outcomes relative to lisinopril. These findings suggest that the recently described drug interaction between clopidogrel and prodrug ACE inhibitors is of little clinical relevance.

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Rates of Hyperkalemia after Publication of the Randomized Aldactone Evaluation Study

Abstract: The publication of RALES was associated with abrupt increases in the rate of prescriptions for spironolactone and in hyperkalemia-associated morbidity and mortality. Closer laboratory monitoring and more judicious use of spironolactone may reduce the occurrence of this complication.

Cited by 1,537 publications

References 25 publications

Use of Mineralocorticoid Receptor Antagonists in Patients With Heart Failure and Comorbid Diabetes Mellitus or Chronic Kidney Disease

Use of Mineralocorticoid Receptor Antagonists in Patients With Heart Failure and Comorbid Diabetes Mellitus or Chronic Kidney Disease

Mineralocorticoid receptor antagonists for heart failure: a real‐life observational study

A population‐based study of the drug interaction between clopidogrel and angiotensin converting enzyme inhibitors

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