Marco Trevisan

Incidence, predictors and clinical management of hyperkalaemia in new users of mineralocorticoid receptor antagonists: Real-world association of hyperkalaemia with MRA use

Concerns for hyperkalaemia limit the use of mineralocorticoid receptor antagonists (MRAs). The frequency of MRA‐associated hyperkalaemia in real‐world settings and the extent of subsequent MRA discontinuation are poorly quantified.

A real-world cohort study on the quality of potassium and creatinine monitoring during initiation of mineralocorticoid receptor antagonists in patients with heart failure

Aims Clinical heart failure (HF) guidelines recommend monitoring of creatinine and potassium throughout the initial weeks of mineralocorticoid receptor antagonists (MRAs) therapy. We here assessed the extent to which this occurs in our health care. Methods and results Observational study in 2007-2010 HF patients starting MRA therapy in Stockholm, Sweden. Outcomes included potassium and creatinine laboratory testing before MRA initiation and in the early (Days 1-10) and extended (Days 11-90) post-initiation periods. Exclusion criteria considered death/hospitalization within 90 days, and lack of a second MRA dispense. Of 4036 HF patients starting on MRA, 45% were initiated from a hospital, 24% from a primary care centre, and 30% from other private centres. Overall, 89% underwent pre-initiation testing, being more common among hospital (97%) than for primary care (74%) initiations. Only 24% were adequately monitored in all three recommended intervals, being again more frequent following hospital (33%) than private (21%) or primary care (17%) initiations. In multivariable analyses, adequate monitoring was more likely for hospital [odds ratio (OR) 2.85, 95% confidence interval (95% CI) 2.34-3.56] initiations, and for patients with chronic kidney disease (OR 1.79, 95% CI 1.30-2.43) and concomitant use of angiotensin-converting enzyme (OR 1.27, 95% CI 1.05-1.52), angiotensin receptor blockers (OR 1.19, 95% CI 1.01-1.40) or beta-blockers (OR 1.65, 95% CI 1.22-2.26). Age, sex, and prescribing centre explained a small portion of adequate monitoring (c-statistic 0.63). Addition of comorbidities and medications improved prediction marginally (c-statistic 0.65). Conclusion Although serum potassium and creatinine monitoring before MRA initiation for HF is frequent, rates of post-initiation monitoring remain suboptimal, especially among primary care centres.

Incident Atrial Fibrillation and the Risk of Stroke in Adults with Chronic Kidney Disease The Stockholm CREAtinine Measurements (SCREAM) Project

BACKGROUND AND OBJECTIVES Patients with CKD have a high risk of atrial fibrillation. Both CKD and atrial fibrillation are associated with higher risk of stroke and death. However, the effect of incident atrial fibrillation on stroke risk among patients with CKD is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Our study included adults with CKD (eGFR<60 ml/min per 1.73 m2) without previously documented atrial fibrillation who had been in contact with health care in Stockholm, Sweden during 2006-2011. Incident atrial fibrillation was identified by administrative diagnostic codes in outpatient or inpatient care and treated as a time-updated exposure in the analysis of stroke and death risk. Stroke events and deaths were ascertained from regional and national registers with complete coverage. Covariates included demographics, comorbidities, therapeutic procedures, and medications. Multivariable Cox regression analysis and competing risk analysis (accounting for death) were used to estimate the association between incident atrial fibrillation and stroke. RESULTS Among 116,184 adults with CKD, 13,412 (12%) developed clinically recognized atrial fibrillation during a mean follow-up of 3.9 years (interquartile range, 2.3-5.7 years). Incidence of atrial fibrillation increased across lower eGFR strata: from 29.4 to 46.3 atrial fibrillations per 1000 person-years in subjects with eGFR=45-60 and <30 ml/min per 1.73 m2, respectively; 1388 (53.8 per 1000 person-years) cases of stroke and 5592 (205.1 per 1000 person-years) deaths occurred after incident atrial fibrillation compared with 6850 (16.6 per 1000 person-years) cases of stroke and 28,613 (67.5 per 1000 person-years) deaths during periods without atrial fibrillation. After adjustment, incident atrial fibrillation was associated with higher risk of stroke (hazard ratio, 2.00; 95% confidence interval, 1.88 to 2.14) and death (hazard ratio, 1.76; 95% confidence interval, 1.71 to 1.82). This was attributed to both ischemic stroke (hazard ratio, 2.11; 95% confidence interval, 1.96 to 2.28) and intracranial bleeds (hazard ratio, 1.64; 95% confidence interval, 1.42 to 1.90). Stroke risk was similar across all eGFR strata. In competing risk analyses accounting for death, the association between incident atrial fibrillation and stroke was attenuated but remained higher (subhazard ratio, 1.49; 95% confidence interval, 1.39 to 1.60). CONCLUSIONS Patients with CKD who develop atrial fibrillation are at higher risk of stroke and death.

Dyskalemias and adverse events associated with discharge potassium in acute myocardial infarction

Background The incidence of dyskalemias and associated outcomes in acute myocardial infarction (AMI) are unknown in real‐world settings and likely differ from the controlled environment of randomized controlled trials. Methods We examined consecutive survivors of an AMI during 2006‐2011 in SWEDEHEART registry and with plasma potassium at discharge (exposure). Study outcomes were 1‐year risk of hyperkalemia (potassium >5.0 mmol/L), hypokalemia (potassium <3.5 mmol/L), and others (1‐year risk of death, new myocardial infarction, heart failure, and de novo atrial fibrillation). Covariates included demographics, comorbidities, hospital procedures, and medications. Results We included 4,861 patients (65% male, age 71.4 ± 12.6 years) with mean discharge potassium of 4.0 ± 0.4 mmol/L. Within 1 year, 784 (16.1%) new hyperkalemic and 991 (20.4%) new hypokalemic events occurred. Discharge potassium and kidney dysfunction were independent predictors of their occurrence. Compared with discharge potassium of 4.0 to <4.5 mmol/L, the adjusted risk of incident hyperkalemia was 1.71 (95% confidence interval 1.41‐2.06) for potassium of 4.5‐5.0 mmol/L and 2.38 (1.69‐3.35) for potassium of >5.0 mmol/L; the adjusted risk of incident hypokalemia was 1.43 for potassium of 3.5 to <4.0 mmol/L (1.23‐1.66) and 3.12 (2.58‐3.77) for potassium of <3.5 mmol/L. A U‐shaped association was observed between discharge potassium and the risk of death (n = 718), with increased hazards for potassium <3.5 and >4.5 mmol/L. No association was found between discharge potassium and the risk of new myocardial infarction, heart failure, or de novo atrial fibrillation. Conclusions Among real‐world AMI survivors, both hyperkalemia and hypokalemia are frequent. Discharge potassium and kidney function strongly predicted their occurrence, as well as the 1‐year risk of death.