Use of guideline-recommended medical therapy in patients with heart failure and chronic kidney disease: from physician's prescriptions to patient's dispensations, medication adherence and persistence

Abstract

Aim: Half of heart failure (HF) patients have chronic kidney disease (CKD) complicating their pharmacological management. We evaluated physicians' and patients' patterns of use of evidence-based medical therapies in HF across CKD stages.

Methods and results: We studied HF patients with reduced (HFrEF) and mildly reduced (HFmrEF) ejection fraction enrolled in the Swedish Heart Failure Registry in 2009-2018. We investigated the likelihood of physicians to prescribe guideline-recommended therapies to patients with CKD, and of patients to fill the prescriptions within 90 days of incident HF (initiating therapy), to adhere (proportion of days covered ≥80%) and persist (continued use) on these treatments during the first year of therapy. We identified 31 668 patients with HFrEF (median age 74 years, 46% CKD). The proportions receiving a prescription for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (ACEi/ARB/ARNi) were 96%, 92%, 86%, and 68%, for estimated glomerular filtration rate (eGFR) ≥60, 45-59, 30-44, and <30 ml/min/1.73 m² , respectively; for beta-blockers 94%, 93%, 92%, and 92%, for mineralocorticoid receptor antagonists (MRAs) 45%, 44%, 37%, 24%; and for triple therapy (combination of ACEi/ARB/ARNi + beta-blockers + MRA) 38%, 35%, 28%, and 15%. Patients with CKD were less likely to initiate these medications, and less likely to adhere to and persist on ACEi/ARB/ARNi, MRA, and triple therapy. Among stoppers, CKD patients were less likely to restart these medications. Results were consistent after multivariable adjustment and in patients with HFmrEF (n = 15 114).

Conclusions: Patients with HF and CKD are less likely to be prescribed and to fill prescriptions for evidence-based therapies, showing lower adherence and persistence, even at eGFR categories where these therapies are recommended and have shown efficacy in clinical trials.

Keywords: Angiotensin receptor-neprilysin inhibitors; Beta-blockers; Chronic kidney disease; Heart failure; Mineralocorticoid receptor antagonists; Renin-angiotensin-aldosterone-system inhibitors.

Figure 1

Percentages of issued prescriptions at register entry (light bars) and filled prescriptions (i.e. initiation of treatments) within 90 days after index date (dotted dark bars) by estimated glomerular filtration rate (eGFR) strata among patients with heart failure with reduced ejection fraction (HFrEF). ACEi, angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor blocker; ARNi, angiotensin receptor–neprilysin inhibitor; MRA, mineralocorticoid receptor antagonist.

Figure 2

Multivariable adjusted odds ratios (OR) (and 95% confidence intervals [CI]) for being prescribed and filling the prescription of guideline‐recommended therapies in patients with heart failure with reduced ejection fraction and differing estimated glomerular filtration rate (eGFR) categories. ACEi, angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor blocker; ARNi, angiotensin receptor–neprilysin inhibitor; MRA, mineralocorticoid receptor antagonist. *Adjusted for age, sex, hospitalization at index, heart failure duration, anaemia, atrial fibrillation, cerebrovascular disease, chronic obstructive pulmonary disease, diabetes mellitus, dilated cardiomyopathy, hypertension, ischaemic heart disease, liver disease, peripheral artery disease, valvular disease, cancer, coronary revascularization, devices (cardiac resynchronization therapy, implantable cardioverter‐defibrillator, or pacemaker), prescription for digoxin, diuretics, statins, anticoagulants, antiplatelets, or nitrates at index, heart rate, systolic and diastolic blood pressure, haemoglobin, highest achieved education, civil status, income, and year of index category.

Figure 3

(A) Multivariable adjusted odds ratios (OR) (and 95% confidence intervals [CI]) for low adherence (proportion of days covered <80%) to guideline‐recommended therapies during the first year of therapy in patients with heart failure with reduced ejection fraction and differing categories of estimated glomerular filtration rate (eGFR). (B) Absolute risks and multivariable adjusted OR (with 95% CI) for non‐persistence (i.e. treatment discontinuation) to guideline‐recommended therapies during the first year of therapy in patients with heart failure with reduced ejection fraction and differing eGFR categories. ACEi, angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor blocker; ARNi, angiotensin receptor–neprilysin inhibitor; MRA, mineralocorticoid receptor antagonist. *Adjusted for age, sex, hospitalization at index, heart failure duration, anaemia, atrial fibrillation, cerebrovascular disease, chronic obstructive pulmonary disease, diabetes mellitus, dilated cardiomyopathy, hypertension, ischaemic heart disease, liver disease, peripheral artery disease, valvular disease, cancer, coronary revascularization, devices (cardiac resynchronization therapy, implantable cardioverter‐defibrillator, or pacemaker), prescription for digoxin, diuretics, statins, anticoagulants, antiplatelets, or nitrates at index, heart rate, systolic and diastolic blood pressure, haemoglobin, highest achieved education, civil status, income, and year of index category. **Takes into account censoring and the competing risk of death.