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  • 1.
    Jonsson, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Norberg, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Bergdahl, Ellinor
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Lindmark, Krister
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Obstacles to mineralocorticoid receptor antagonists in a community-based heart failure population2018Ingår i: Cardiovascular therapeutics, ISSN 1755-5914, Vol. 36, nr 5, artikel-id e12459Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM: Previous studies and national assessments indicate an undertreatment of mineralocorticoid receptor antagonists (MRA) in heart failure with reduced ejection fraction (HFrEF). This study aimed to investigate why MRA is not used to full extent.

    METHODS: A complete community-based heart failure population was studied. Several variables were collected, and medical records were scrutinized to identify reasons for not prescribing MRA.

    RESULTS: Of 2029 patients, 812 had EF ≤40%. Five hundred and fifty-three patients (68%) tried MRA at some point but 184 of these (33%) discontinued therapy. There were 259 patients that never tried MRA with 177 with a listed explanation or contraindication. Eighty-two patients, 10% of the total HFrEF population, had no clear contraindications. They were older and had less HF hospitalizations compared to patients on MRA (P < 0.05) and 32% did not have any follow-up at the cardiology clinic. Contraindications to MRA were renal dysfunction (93 patients), hypotension (28 patients), and hyperkalemia (25 patients). Only six patients had hyperkalemia without renal dysfunction. Of the patients with renal dysfunction, 66 (72%) had eGFR >30 mL/min.

    CONCLUSIONS: The reasons why MRA are underutilized were mainly because of contraindications. However, the data suggest that physicians are overly cautious about moderately reduced kidney function. There seems to be a 10%-18% avoidable undertreatment with MRA, especially for elderly patients that are admitted to the hospital for other reasons than heart failure. This suggests that patients with heart failure would benefit from routine follow-up at a cardiology clinic.

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  • 2.
    Jonsson, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Norberg, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Valham, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Bergdahl, Ellinor
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Lindmark, Krister
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Mineralocorticoid receptor antagonists use in patients with heart failure and impaired renal function2021Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 16, nr 10, artikel-id e0258949Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims: Impaired renal function is a major contributor to the low proportion of mineralocorticoidreceptor antagonist (MRA) treatment in patients with heart failure with reduced ejection fraction(HFrEF). Our aims were to investigate the impact of MRA treatment on all-cause mortalityand worsening renal function (WRF) in patients with HFrEF and moderately impairedrenal function.

    Methods: Retrospective data between 2010–2018 on HFrEF patients from a single-centre hospitalwith estimated glomerular renal function (eGFR) < 60 ml/min/1.73 m2 were analysed. WRF was defined as a decline of by eGFR > 20%.

    Results: 416 patients were included, 131 patients on MRA and 285 without MRA, mean age was 77years (SD ± 9) and 82 years (SD ± 9), respectively. Median follow-up was 2 years. 128patients (32%) experienced WRF, 25% in the MRA group and 30% in patients without MRA(p = 0.293). In multivariable analysis, hospitalization for heart failure and systolic blood pressurewere associated with WRF (p = 0.015 and p = <0.001), but not use of MRA (p = 0.421).MRA treatment had no impact on the risk of adjusted all-cause mortality (HR 0.93; 95% CI,0.66–1.32 p = 0.685). WRF was associated with increased adjusted risk of all-cause mortality(HR 1.43; 95% CI, 1.07–1.89 p = 0.014). Use of MRA did not increase the adjusted overallrisk of mortality even when experiencing WRF (HR 1.15; 95% CI, 0.81–1.63 p = 0.422).

    Conclusion: In this cohort of elderly HFrEF patients with moderately impaired renal function, MRA didnot increase risk for WRF or all-cause mortality.

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  • 3.
    Jonsson, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Viklund, Ida
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Jonsson, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Valham, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Bergdahl, Ellinor
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Lindmark, Krister
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Norberg, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Comparison of creatinine-based methods for estimating glomerular filtration rate in patients with heart failure2020Ingår i: ESC Heart Failure, E-ISSN 2055-5822, Vol. 7, nr 3, s. 1150-1160Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims: Glomerular filtration rate is an important factor in management of heart failure (HF). Our objective was to validate eight creatinine-based equations for estimating glomerular filtration rate (eGFR) in an HF population against measured glomerular filtration rate.

    Methods and results: One hundred forty-six HF patients (mean age 68 +/- 13 years, mean left ventricular ejection fraction 45% +/- 15) within a single-centre hospital that underwent Cr-51-EDTA clearance between 2010 and 2018 were included in this retrospective study. eGFR was estimated by means of Cockcroft-Gault ideal and actual weight, the Modification of Diet in Renal Disease Study (MDRD), simplified MDRD with isotope dilution mass spectroscopy traceable calibration, the Chronic Kidney Disease Epidemiology Collaboration, revised Lund-Malmo, full age spectrum, and the Berlin Initiative Study 1. Mean measured glomerular filtration rate was 42 mL/min/1.73 m(2). Pearson's correlation coefficient (r) had the highest precision for MDRD (r = 0.9), followed by revised Lund-Malmo (r = 0.88). All equations except MDRD (mean difference -4.8%) resulted in an overestimation of the renal function. The accuracy was below 75% for all equations except MDRD.

    Conclusions: None of the exclusively creatinine-based methods was accurate in predicting eGFR in HF patients. Our findings suggest that more accurate methods are needed for determining eGFR in patients with HF.

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  • 4.
    Jonsson, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Wessberg, Gustav
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Norberg, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Söderström, Adrian
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Valham, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Bergdahl, Ellinor
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Lindmark, Krister
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Motives, frequency, predictors and outcomes of MRA discontinuation in a real-world heart failure population2022Ingår i: Open heart, E-ISSN 2053-3624, Vol. 9, nr 2, artikel-id e002022Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Mineralocorticoid receptor antagonists (MRAs) reduce mortality and morbidity in patients with heart failure and reduced ejection fraction (HFrEF), but are largely underused. We evaluated the frequency, motives, predictors and outcomes of MRA discontinuation in a real-world heart failure population.

    Methods and results: This was a single-centre, retrospective cohort study where medical record-based data were collected on patients with HFrEF between 2010 and 2018. In the final analysis, 572 patients were included that comprised the continued MRA group (n=275) and the discontinued MRA group (n=297). Patients that discontinued MRA were older, had a higher comorbidity index and a lower index estimated glomerular filtration rate (eGFR). Predictors of MRA discontinuations were increased S-potassium, lower eGFR, lower systolic blood pressure, higher frequency of comorbidities and a higher left ventricular ejection fraction. The most common reason for MRA discontinuation was renal dysfunction (n=97, 33%) with 59% of these having an eGFR <30 mL/min/1.73m 2, and elevated S-potassium (n=71, 24%) with 32% of these having an S-potassium >5.5 mmol/L. Discontinuation of MRA increased the adjusted risk of all-cause mortality (HR 1.48; 95% CI 1.07 to 2.05; p=0.019).

    Conclusions: Half of all patients with HFrEF initiated on MRA discontinued the treatment. A substantial number of patients discontinued MRA without meeting the guideline-recommended levels of eGFR and S-potassium where mild to moderate hyperkalaemia seems to be the most decisive predictor. Further, MRA discontinuation was associated with increased adjusted risk of all-cause mortality.

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  • 5.
    Jonsson, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Wessberg, Gustav
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Norberg, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Söderström, Adrian
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Valham, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Bergdahl, Ellinor
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Lindmark, Krister
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Motives, predictors, and outcomes of MRA discontinuation in a real-world heart failure populationManuskript (preprint) (Övrigt vetenskapligt)
  • 6.
    Jonsson Holmdahl, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Mineralocorticoid receptor antagonists in heart failure: exploring the gap between guideline-directed medical therapy and real-world practice2021Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Heart failure is the possible end-result of a variety of different diseases, where ischemic heart disease and hypertension are the most common causes in high income countries. In Sweden, heart failure has a prevalence of 2% in the adult population and rises to over 10% among people over 70 years of age. The 5-year all-cause mortality is about 50%. To put in context, the age-adjusted 5-year mortality, first hospitalization rate and premature life-year loss were shown to be similar to those of the most common forms of cancer combined. The triad of Angiotensin-Converting Enzyme Inhibitors (ACEIs) or Angiotensin II Receptor Blockers (ARBs), Beta-blockers (BBs), and Mineralocorticoid Receptor Antagonists (MRAs) are recommended in all patients with heart failure with reduced ejection fraction (HFrEF) to decrease mortality and morbidity rates. While most eligible patients get access to treatment with ACEIs/ARBs and BBs, national and international registry and observational studies have shown that MRA treatment is largely underused in patients with HFrEF. Treatment with MRAs has shown a 15-30% relative risk reduction of all-cause mortality inpatients with HFrEF at a follow-up time of 16 to 24 months, but not even half of all eligible patients receive this treatment. The aim of this theses was to explore the pattern of MRA use in a real-world heart failure population and the reasons for MRA underuse.

    With an observational retrospective study design, patients were included if they were diagnosed with heart failure at the Heart Centre or Department of Internal Medicine between January 2010 and January 2018. All patients were residents within the catchment area of the Umeå University Hospital, Sweden, and were identified by the hospital’s medical records. All data were collected from medical records. Index data were collected at the time of diagnosis, and follow-up data were collected by the journal entry closest to the end of the data collection period (2016-2018).

    From the medical record content analysis, we found that contraindications including renal dysfunction, hypotension and hyperkalemia were the most common reasons for not receiving treatment with MRAs. However, almost half of those patients did not meet the guideline-directed contraindications. After excluding patients with contraindications, the underutilization of MRAs was 10%. Patients without MRAs had been hospitalized for heart failure to a much lesser extent. It is possible that this group of patients were often overlooked, which is supported by the finding that nearly one-third of these patients never had a follow-up at the cardiology clinic. Overall, we estimated that about 60% of thepatients with HFrEF would tolerate MRA treatment in the long-term, but only about 45% of the patients with HFrEF in our population were prescribed and maintained on MRAs.

    Since renal dysfunction was the most common reason for not initiating MRA treatment, we wanted to evaluate how accurate eight different creatinine-based equations for estimated glomerular filtration rate (eGFR) were in heart failure patients. We showed that none of the exclusively creatinine-based equations for eGFR were accurate in predicting mGFR. All creatinine-based eGFR equations overestimated the renal function. Our findings suggests that more accurate methods are needed for determining eGFR in patients with heart failure since overestimation causes an unnecessary risk of serious adverse effects and may also lead to patients not receiving optimal guideline-directed medical therapy.

    We also found that half of all patients initiated on MRAs discontinued treatment. The most common reasons for discontinuation were renal dysfunction and elevated serum-potassium but again, a majority of those did not meet guideline-directed contraindications. Independent predictors of MRA discontinuation were lower eGFR, increased serum-potassium, lower blood pressure, higher comorbidity index and higher left ventricular ejection fraction. Patients who discontinued MRAs had a higher risk of all-cause mortality after adjusting forrelevant covariates. One-third of all patients with moderately impaired renalfunction developed worsening renal function (WRF) but use of MRAs did not impact the risk. Furthermore, use of MRAs did not increase the adjusted overallrisk of mortality even when experiencing WRF.

    In conclusion, there seems to be a substantial avoidable under-treatment with MRAs especially for elderly patients that are admitted to the hospital for reasons other than heart failure as well as in patients with moderately impaired renal dysfunction with mild hyperkalemia. We suggest that the risk of inadequate means of follow-up restrains optimal use of MRAs, especially in patients with moderately impaired renal function and or mild hyperkalemia that require frequent and regular laboratory monitoring to assure the safe use of MRAs. In addition, better methods are needed to accurately estimate renal function in heart failure patients. These findings contribute to the understanding of the underlying reasons behind the gap between the guideline-directed use of MRAs and real-world practice.

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