Differences in guideline-recommended heart failure medication between Dutch heart failure clinics: an analysis of the CHECK-HF registry

Heart failure (HF) is associated with a high symptom burden, morbidity and mortality [1‐3]. Optimising guideline-recommended HF therapies improve health-related quality of life and prognosis [4‐6]. However, in real-world practice, implementation and adherence to recommended treatment, a benchmark of quality of care, are suboptimal. A recent analysis of medication profiles of 22,476 unselected patients with a diagnosis of HF at hospital discharge between 2001 and 2015 derived from the Dutch PHARMO Database Network showed only partial improvement of prescribed HF medication over time [7]. The percentage of patients prescribed the combination of a beta blocker and an angiotensin-converting-enzyme (ACE) inhibitor or angiotensin receptor blocker increased from 24 to approximately 45% within this 15-year period. The percentage of patients who also used a mineralocorticoid receptor antagonist (MRA) reached approximately 20%. Notably, the probability of being prescribed these combinations decreased with increasing age and there was no significant increase in MRA prescriptions. Moreover, recent real-world registries demonstrated underuse of HF therapies despite clear evidence-based recommendations [8‐10].

In fact, randomised clinical trials and surveys did not represent real-life HF populations [11‐13]. Moreover, the distribution of recommended HF treatment and considerable practice variation between regions and hospitals are largely unexplained, but also unexplored.

In a large-scale real-world registry at Dutch HF outpatient clinics, we therefore investigated the differences in medical HF therapies and determinants of prescription of individual, recommended HF drugs in HFrEF patients [14, 15] among 34 HF clinics in the Netherlands.

The design and methods of the CHECK-HF (Chronic Heart failure ESC guideline-based Cardiology practice Quality project) registry have been published in detail earlier [14]. Briefly, the CHECK-HF registry consists of 10,910 patients with chronic HF from a total of 34 participating centres (40% of the 86 centres in the Netherlands of which 60 have an outpatient HF unit) (Fig. 1). Patients were included cross-sectionally based on the available records of these patients. Between 2013 and 2016, all participating centres included patients diagnosed with HF based on the 2012 ESC guidelines on HF (i.e. based on symptoms and echo parameters) who were seen at the outpatient HF clinic (96%) or general cardiology outpatient clinic (4%) if no specific HF clinic was present.

Baseline patient characteristics, aetiology of HF, comorbidities, basic echocardiographic and electrocardiographic (ECG) parameters, laboratory markers, pacemaker, implantable cardioverter-defibrillator treatment and cardiac resynchronisation therapy as well as prescription rates of medication (drug name, dosage and frequency and total daily dose) were recorded. The target doses of guideline-recommended HF medication are presented in Suppl. Table 1. Drug doses were calculated compared with the recommended dose and according to guidelines as a daily dose or %, percentage of actual recommended daily dose.

Furthermore, contraindications and intolerance as indicated by the treating physician were collected. No predefined rules were applied to determine absolute contraindications.

In 283 (2.6%) patients, recording of ejection fraction in the database was insufficient to classify patients, so these patients were excluded from this analysis.

Based on echocardiographic results, the remaining 10,627 patients were divided based on left ventricular ejection fraction (LVEF) or visual assessment of the function of the left ventricle into HF with preserved ejection fraction (HFpEF) (LVEF ≥50%, n = 2,267 (21%)) and HF with reduced ejection fraction (HFrEF: LVEF <50%, n = 8,360 (79%)), according to the 2012 ESC HF guidelines [4].

For a sub-analysis according to the newer 2016 ESC HF guidelines, patients with an assessed LVEF <50% were categorised into HF with mid-range ejection fraction (HFmrEF) (LVEF 40–49%, n = 1,574 (19%)), HFrEF (LVEF <40%, n = 5,701 (68%)), and into HF with a semi-quantitative analysis of the systolic left ventricular function only (n = 1,085 (13%)). In the current analyses, we focused on the prescribed HF medication in HFrEF patients (LVEF <50%).

The Medical Research Ethics Committee of the Maastricht University Medical Center, the Netherlands, provided ethical approval for anonymously analysing existing patient data. No informed consent of the participants in this registry was required.

Baseline characteristics of the total group of 8,360 HFrEF patients are shown in Table 1. Mean age was 72.3 ± 11.8 years (ranging between 69.1 ± 11.9 and 76.6 ± 10.0 between the clinics), 63.9% were men (ranging between 54.3 and 78.1%), 27.3% were in New York Heart Association (NYHA) class III/IV (ranging between 8.8 and 62.1%) and the average estimated glomerular filtration rate (eGFR) was 59.6 ± 24.6 ml/min (ranging between 45.7 ± 23.5 and 97.1 ± 16.5). Between centres, a wide range of prevalence rates with regard to ischaemic aetiology of HF, atrial fibrillation and comorbidities were found, as presented in Table 1. When subdividing HF patients in LVEF groups according to ESC guidelines 2016, HFmrEF patients (n = 1,574) were more often female, had less often ischaemic aetiology, less wide QRS complex and more often atrial fibrillation, hypertension and chronic obstructive pulmonary disease (COPD), all compared with HFrEF patients (n = 5,701). However, in both groups, there was a wide variation of all baseline characteristics between centres (Suppl. Tables 2 and 3).

From our outpatient HF registry in a representative number of centres in the Netherlands, we demonstrated that demography, HF characteristics and comorbidities in HFrEF patients widely varied between those centres. Also, the prescription rates and prescribed dosages of guideline-recommended HF medication varied significantly, both for HFrEF and HFmrEF patients. Those variations between hospitals could not be explained by differences in baseline characteristics of participating HF patients.

Overall, we found higher prescription rates of recommended HF medication than in previous registries, which may be related to the delivery of specialist outpatient HF care in the vast majority of patients [10].

The CHECK-HF registry is a large-scale real-world registry of HF outpatient clinics in the Netherlands reflective of Western European countries. However, some limitations should be mentioned, such as the cross-sectional design limiting follow-up data on patient outcomes. Some missing data exists, which might influence results. Our registry included only patients seen in secondary, but not in primary care, which limits the generalisability of our findings to the primary care setting. Information on actual protocols of diagnostic workup and medical decision-making strategies in centres was not collected. Notably, the CHECK-HF inclusion period was from 2013 till end of 2016, in which the CONNECT programme for Heart failure regional care had been in the initial phase of implementation in regions. Therefore, we have not collected data on adoption of the CONNECT Heart Failure programme in the centres. Strengths of the study are the reflection of the true practice of large scale nationwide outpatient HF management with detailed information on medication prescription and dosage.

In this Dutch real-world registry of outpatient HF population, wide between-clinic ranges of demography, severity of heart failure and comorbidities of HF patients were observed. Also the prescription rates and prescribed dosages of guideline-recommended HF medication differed significantly, not fully explained by differences in the patient profiles. Thus, future research should lead to strategies to improve management of HF patients including reduction of practice variation.