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

Abstract

AimsWe 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.

Medication adherence, related factors and outcomes among patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension: a systematic review

“…In chronic heart failure, MA was largely explored using a cutoff MA of 80% and was reported as nonoptimal at 1 year (around 17% to 39% for nonadherent patients, depending on the therapeutic class) [ 51 , 52 ]. In those studies, MA worsens with the passing years and the number of medications (42% and 5% were adherent to dual and triple heart failure therapy) [ 51 , 52 ]. Another well-described factor impacting MA in cardiovascular disease is the high drug intake frequency [ 51 , 53 , 54 ].…”

Cardiac contractility modulation in patients with heart failure: The added value of cardiac rehabilitation in identification, management, and follow-up

“…Theoretical best HF therapy is often not feasible due to side effects (e.g., symptomatic hypotension, hyperkalemia), which cannot allow to reach the maximum expected dosage in all patients [ 4 , 5 ]; conversely, only 30 % of all HF patients meet the criteria for receiving device therapy, such as cardiac resynchronization therapy (CRT) [ 6 ].…”

Guideline implementation, drug sequencing, and quality of care in heart failure: design and rationale of TITRATE‐HF

“…3 In the context of persistently high rates of mortality and hospitalization associated with HFrEF, data from CHECK-HF and other real-world registries highlight the urgency towards improving GDMT implementation and ensuring that all eligible patients with HFrEF in routine clinical practice receive the recommended four drug classes. [3][4][5][6][7] The most recent European Society of Cardiology (ESC) HF 2021 guideline recommends the four life-saving drug classes to be administered to all eligible patients with HFrEF and that each drug be initiated without significant delay. 1,8 Multiple studies have supported this recommendation and show the link between a short implementation time-frame and reduced mortality, [9][10][11] of which the results were confirmed in the STRONG-HF trial.…”

“…In the Netherlands, the CHECK‐HF registry has shown an overall good GDMT prescription rate; however, only a third of the patients with HFrEF used all GDMT in any dose 3 . In the context of persistently high rates of mortality and hospitalization associated with HFrEF, data from CHECK‐HF and other real‐world registries highlight the urgency towards improving GDMT implementation and ensuring that all eligible patients with HFrEF in routine clinical practice receive the recommended four drug classes 3–7 …”

“… 3 In the context of persistently high rates of mortality and hospitalization associated with HFrEF, data from CHECK‐HF and other real‐world registries highlight the urgency towards improving GDMT implementation and ensuring that all eligible patients with HFrEF in routine clinical practice receive the recommended four drug classes. 3 , 4 , 5 , 6 , 7 …”