Characterization of Mineralocorticoid Receptor Antagonist Therapy Initiation in High-Risk Patients With Heart Failure

Abstract

Background Heart failure (HF) guidelines recommend routine monitoring of serum potassium and renal function in patients treated with a mineralocorticoid receptor antagonist (MRA). How these recommendations are implemented in high risk patients or according to setting of drug initiation is poorly characterized. Methods and Results We conducted a retrospective cohort study of Medicare beneficiaries linked to laboratory data in 10 states with prevalent HF as of July 1, 2011 and incident MRA use between May 1 and September 30, 2011. Outcomes included laboratory testing prior to MRA initiation and in the early (day 1–10) and extended (day 11–90) post-initiation periods, based on setting of drug initiation and presence of renal insufficiency. Additional outcomes included abnormal laboratory results and adverse events proximate to MRA initiation. Of 10,443 Medicare beneficiaries with HF started on an MRA, 19.7% were initiated during a hospitalization. Appropriate follow-up lab testing across all time periods occurred in 25.2% of patients with inpatient initiation compared with 2.8% of patients begun as an outpatient. Patients with chronic kidney disease (CKD) had higher rates of both hyperkalemia and acute kidney failure in the early (1.3% and 2.7%, respectively) and extended (5.6% and 9.8%, respectively) post-initiation periods compared with those without CKD. Conclusions Patients initiated on MRA therapy as an outpatient had extremely poor rates of guideline indicated follow-up laboratory monitoring after drug initiation. In particular, patients with CKD are at high risk for adverse events after MRA initiation. Quality improvement initiatives focused on systems to improve appropriate laboratory monitoring are needed.

Incidence, predictors and clinical management of hyperkalaemia in new users of mineralocorticoid receptor antagonists

“…Most events occurred within the first 3 months of therapy, which again agrees with the experience of MRA trials: in the Randomized Aldactone Evaluation Study (RALES) trial, the greatest change in K + occurred within the first 4 weeks following initiation of spironolactone . This finding underscores the importance of early monitoring of K + after initiation of an MRA, something that despite recommended by current guidelines is not taking place in practice …”

“…Randomized controlled trials of MRAs report rates of hyperkalaemia that may not reflect the heterogeneous reality of clinical practice . ‘Real‐world’ observational studies show suboptimal MRA use, dose titration and poor clinical follow‐up that may increase hyperkalaemia risk. Current management of hyperkalaemia is most often centred on eliminating modifiable causes, e.g.…”

Incidence and determinants of hyperkalemia and hypokalemia in a large healthcare system

“…We observe that approximately 9% of patients with diabetes, 5% of patients with HF or CKD, all at high-risk of hyperkalemia did not undergo annual K screening. Current guidelines recommend to closely monitoring potassium during the initiation of RAASi therapy [47][48][49], and this observation is in line with real-world data suggesting that adequate monitoring is not taking place [8][9][10].…”

“…Differences in reported rates of dyskalemia may be explained by the inclusion of more heterogeneous populations [7] and diverse clinical practices, such as variations in the frequency of potassium monitoring, which is reported as suboptimal in real-world settings [8][9][10]. Studies with broader coverage, such as those derived from healthcare records may be relevant to inform clinical practice.…”

Mineralocorticoid receptor antagonists and kidney diseases: pathophysiological basis

“…A large retrospective cohort study conducted among Medicare patients with heart failure reported that the rate of appropriate monitoring of serum potassium levels was very low. 186 Appropriate monitoring was conducted more frequently among CKD patients but was still low. 186 Such nonappropriate serum potassium monitoring certainly contributes to adverse events, because clinicians are unable to adjust their prescription according to laboratory findings.…”