Adherence and persistence to pharmacotherapy in patients with heart failure: a nationwide cohort study, 2014-2020.

AIMS: We aimed to study initiation, adherence, and long-term persistence to beta-blockers (BB), renin-angiotensin system inhibitors (RASi), and mineralocorticoid receptor antagonists (MRA) in a nationwide cohort of patients with heart failure (HF). METHODS: Patients aged 18-80 years in Norway with a first diagnosis of HF from 2014 until 2020 that survived ≥30 days were identified from the Norwegian Patient Registry and linked to the Norwegian Prescription Database. We collected information about BB, RASi [angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARB), and angiotensin receptor-neprilysin inhibitors (ARNI)], and MRA. Dual HF therapy was defined as taking at least two out of three drug classes, whereas triple HF therapy was defined as taking all three. Initiation (time to initiation) and persistence (time to discontinuation using a grace period of 30 days) of HF drugs was calculated by the Kaplan-Meier method, followed to outcome of interest, death, or December 2020. One-year adherence was measured as proportion of days covered (PDC) using a cut-off at 80%. For adherence and persistence measurements, we allowed for maximum 60 days of stockpiling and switching within drug groups. We performed sensitivity analyses to test the robustness of our findings. RESULTS: Out of 54 899 patients included in the cohort, 75%, 69%, and 21% initiated a BB, RASi, and MRA, respectively, whereas 13% did not receive any. Dual and triple HF therapy was prescribed to 61% and 16%, respectively. The proportion of adherent patients during the first year following initiation was 83%, 81%, 84%, and 61% for BB, RASi, ARNI, and MRA, whereas 42% and 5% were adherent to dual and triple HF therapy, respectively. From 2 to 5 years following initiation, persistence decreased from 58% to 38%, 57% to 37%, and 31% to 15% for BB, RASi, and MRA, respectively. Within the RASi group, persistence was higher for ARNI than for ACEI and ARB. There were no major changes in either initiation or adherence of the drug classes from 2014 to 2019, except for an increase in initiation and adherence of MRA. CONCLUSIONS: We found low adherence to dual and triple HF therapies in this nationwide cohort study of newly diagnosed HF patients. Efforts are needed to increase adherence and persistence to HF therapies into clinical practice, emphasizing maintenance of multiple drug therapies in patients with such an indication.

Clinical characteristics and mortality of patients with heart failure in Southern Sweden from 2013 to 2019: a population-based cohort study.

OBJECTIVES: To describe clinical characteristics and prognosis related to heart failure (HF) phenotypes in a community-based population by applying a novel algorithm to obtain ejection fractions (EF) from electronic medical records. DESIGN: Retrospective population-based cohort study. SETTING: Data were collected for all patients with HF in Southwest Sweden. The region consists of three acute care hospitals, 40 inpatient wards, 2 emergency departments, 30 outpatient specialty clinics and 48 primary healthcare. PARTICIPANTS: 8902 patients had an HF diagnosis based on the International Classification of Diseases, Tenth Revision during the study period. Patients <18 years as well as patients declining to participate were excluded resulting in a study population of 8775 patients. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was distribution of HF phenotypes by echocardiography. The secondary outcome measures were 1 year all-cause mortality and HR for all-cause mortality using Cox regression models. RESULTS: Out of 8775 patients with HF, 5023 (57%) had a conclusive echocardiography distributed into HF with reduced EF (35%), HF with mildly reduced EF (27%) and HF with preserved EF (38%). A total of 43% of the cohort did not have a conclusive echocardiography, and therefore no defined phenotype (HF-NDP). One-year all-cause mortality was 42% within the HF-NDP group and 30% among those with a conclusive EF. The HR of all-cause mortality in the HF-NDP group was 1.27 (95% CI 1.17 to 1.37) when compared with the confirmed EF group. There was no significant difference in survival within the HF phenotypes. CONCLUSIONS: This population-based study showed a distribution of HF phenotypes that varies from those in selected HF registries, with fewer patients with HF with reduced EF and more patients with HF with preserved EF. Furthermore, 1-year all-cause mortality was significantly higher among patients with HF who had not undergone a conclusive echocardiography at diagnosis, highlighting the importance of correct diagnostic procedure to improve treatment strategies and outcomes.

Gaps and discontinuation of statin treatment in Norway: potential for optimizing management of lipid lowering drugs.

Aims: In clinical practice, many patients do not reach the recommended treatment targets for LDL-cholesterol levels. We aimed to examine treatment patterns and adherence for patients on lipid lowering drugs in Norway to inform future strategies to improve therapies. Methods and results: We obtained information on all dispensed statins, ezetimibe, and proprotein convertase subtilisin/-kexin 9 (PCSK9) inhibitors 2010-2019 from the Norwegian Prescription Database. Treatment gaps were assessed assuming patients take one tablet per day and were defined to occur if a patient did not refill a prescription when the previous one should have been depleted. Treatment was defined as discontinued when the preceding prescription would have been used and no new subsequent prescription was filled. The mean proportion of days covered (PDC) was calculated by aggregating the total number of tablets dispensed during each calendar year and dividing by 365. Patients 80 years were excluded. A considerable proportion of statin users in Norway had long treatment gaps or discontinuation in treatment. The 19.6% of the patients had treatment gaps of 180 days or more, and 10.8% had gaps or greater than 365 days. Similar results were found for patients on antidiabetics and hypertensives. PDC ranged from 84.9% for simvastatin to 72.2% for ezetimibe (2019). The most common lipid lowering drugs in 2019 were atorvastatin, simvastatin, and ezetimibe. Conclusion: There is a great potential for improving drug adherence and optimizing lipid lowering therapy by switching to more effective statins in greater doses, and more often add ezetimibe and PCSK9 inhibitors to treatment.

A nationwide registry study on heart failure in Norway from 2008 to 2018: variations in lookback period affect incidence estimates.

BACKGROUND: The incidence of heart failure (HF) has declined in Europe during the past two decades. However, incidence estimates from registry-based studies may vary, partly because they depend on retrospective searches to exclude previous events. The aim of this study was to assess to what extent different lookback periods (LPs) affect temporal trends in incidence, and to identify the minimal acceptable LP. Further, we wanted to estimate temporal trends in incidence and prevalence of HF in a nationwide population, using the minimal acceptable LP. METHODS: We identified all in- and out-patient contacts for HF in Norway during 2008 to 2018 from the Norwegian Patient Registry. To calculate the influence of varying LP on incident cases, we defined 2018 with 10 years of LP as a reference and calculated the relative difference by using one through 9 years of lookback. Temporal trends in incidence rates were estimated with sensitivity analyses applying varying LPs and different case definitions. Standardised incidence rates and prevalence were calculated by applying direct age- and sex-standardization to the 2013 European Standard Population. RESULTS: The overestimation of incident cases declined with increasing number of years included in the LP. Compared to a 10-year LP, application of 4, 6, and 8 years resulted in an overestimation of incident cases by 13.5%, 6.2% and 2.3%, respectively. Temporal trends in incidence were affected by the number of years in the LP and whether the LP was fixed or varied. Including all available data mislead to conclusions of declining incidence rates over time due to increasing LPs. CONCLUSIONS: When taking the number of years with available data and HF mortality and morbidity into consideration, we propose that 6 years of fixed lookback is sufficient for identification of incident HF cases. HF incidence rates and prevalence increased from 2014 to 2018. TRIAL REGISTRATION: Retrospectively registered.

Incidence, prevalence, and mortality of heart failure: a nationwide registry study from 2013 to 2016.

AIMS: Large-scaled population studies of incidence and prevalence of heart failure (HF) are needed for the development of healthcare policies and priorities. The aim of this study was to estimate the incidence, prevalence, and all-cause mortality of HF in Norway from 2013 to 2016 on the basis of a national registry. METHODS AND RESULTS: Using data from the nationwide Norwegian Prescription Database, we identified all patients ≥18 years of age in Norway with at least one drug prescription with HF during 2013-2016, defined by 10th revision of the International Classification of Diseases (ICD-10) codes I50, I11, I13, or I42. The individual index date was the date of the first prescription. Patients were followed up until death or end of follow-up (31 October 2017). Annual incidence and prevalence were estimated from 2013 to 2016, using a look-back period starting from 1 March 2008. We calculated standardized estimates by applying direct age and sex standardization to the 2013 European standard population. All-cause mortality from 2013 to 2016 was calculated among the prevalent HF patients. Standardized mortality ratio (SMR) was calculated by indirect standardization using general mortality in the Norwegian population as reference. We identified 54 542 unique patients (58% men) with a first-time diagnosis of HF. The median age was 72 ±14 years, and women were older than men (median age 76 vs. 70 years, respectively). The crude (standardized) incidence of HF was 3.44/1000 (4.23/1000) person-years in 2016 and did not increase over the 4 year period, while the prevalence increased from 2.0% (2.3%) to 2.4% (2.8%). Both incidence and prevalence were higher in men than in women and strongly associated with age. Crude mortality rates in the HF population declined from 94 to 82/1000 person-years from 2013 to 2016, and SMR declined from 2.01 to 1.84. Age-adjusted mortality rates were higher in men than in women. CONCLUSIONS: This nationwide registry study in Norway showed an increase in the prevalence of HF from 2013 to 2016, with stable incidence rates and improved survival.