Overcoming the Clinical Inertia behind Inadequate Adherence to Guideline-Directed Medical Therapy

Heart failure is a clinical syndrome caused by structural and functional cardiac abnormalities that has objective symptoms and signs due to elevated natriuretic peptide levels and pulmonary or systemic congestion [1]. Current international guidelines emphasize the importance of implementing guideline-directed medical therapy (GDMT) at all stages of heart failure treatment. This includes consideration for dosing and adherence, patient education, and ongoing review of treatment goals [2, 3].

The current international GDMT standard of care is the selection of a recommended therapy based on left ventricular ejection fraction. Since the 1990s, the efficacy of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), β-blockers, and mineralocorticoid receptor antagonists (MRAs) have been demonstrated successively. Together, these drugs have been positioned as the standard treatment for heart failure with reduced ejection fraction (HFrEF) as a “triple therapy.” More recently, evidence for the replacement of ACE inhibitors and ARBs with angiotensin receptor neprilysin inhibitors (ARNIs) has been presented, along with the efficacy of sodium-glucose co-transporter 2 inhibitors; these are now positioned as one of the basic drugs recommended for HFrEF treatment. In addition, guidelines recommend hyperpolarization-activated cyclic nucleotide-dependent channel blockers for patients in sinus rhythm with heart rates above 70 beats per minute, diuretics for congestion, and the use of digitalis and vasodilators as adjunctive agents. More recently, soluble guanylate cyclase-stimulating agents have been shown to be effective in certain HFrEF patient populations and are now in clinical use. With the advent of these new heart failure therapies, GDMT has undergone a major transformation from the former triple therapy; now, ARNI, β-blockers, MRAs, and sodium-glucose co-transporter 2 inhibitors are recommended in class I as quadruple therapy (4 pillar) for HFrEF.

In another article in this issue, Rivera-Toquica et al. [4] used Colombian Heart Failure Registry (RECOLFACA) data to investigate compliance with GDMT in the treatment of HFrEF. They found that ACEIs or ARBs were prescribed to 72.3% of patients with HFrEF, β-blockers to 88.9%, MRAs to 67.9%, and ARNIs to 13.1%. Additionally, less than one-third of all patients reached the target dose recommended by the European heart failure guidelines [3]. In Colombia, GDMT for HFrEF – indicating the appropriate use of medications and achievement of target doses – was suboptimal. This inadequate adherence with GDMT is a major challenge there, as well as worldwide. In the Change the Management of Patients with Heart Failure (CHAMP-HF) registry, ACE inhibitors or ARBs were prescribed to 59.9% of patients, β-blockers to 66.8%, and MRAs to only 33.1% [5]. In our registry, ACE inhibitors or ARBs were prescribed in 63.6% of cases, β-blockers in 82.2%, and MRAs in only 56.7% of cases in Japan, which has a super-aged society. However, caution must be exercised in interpreting these retrospective results, and two important factors are essential: clinical inertia and true physiological limitations [6].

Particularly in older patients with HFrEF, comorbidities such as chronic kidney disease and obstructive breathing disorders may prevent appropriate GDMT. Additionally, because life expectancy is short, increasing quality of life may be more important than prolonging life. A Korean study showed that practicing GDMT is important to ensuring a good prognosis even in patients over 80 years of age [7]. Our registry showed similar results (shown in Fig. 1). However, in another registry, the combined event of cardiac death and hospitalization due to worsening heart failure was more common in the GDMT-adherent group of patients older than 80 years [8]. This result is considered to be related to various factors such as pharmacokinetics, interactions, and comorbidities specific to the older adults; in actual clinical settings, treatment strategy is determined not only by scientific principles but also involves the subjective element of “adjustment.”

Recently, several efforts have been made to improve compliance with GDMT to overcome clinical inertia. Programs led by medical staff, such as nurses and pharmacists, have been shown to have the potential to lead to improved GDMT practices and better outcomes [9, 10]. It may be important for medical teams, including other medical staff, to repeatedly review physician’s prescriptions to ensure that GDMT compliance is being practiced where applicable.