Optimizing Guideline-Directed Medical Therapy for Heart Failure ― Challenges and Strategies ―
論文ID: CJ-23-0828
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論文ID: CJ-23-0828
The abundant evidence of pharmacologic therapies that extend survival, reduce hospitalization, and improve patient-reported quality of life (QOL) is the basis for contemporary guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF).1 GDMT comprises 4 drug classes: renin-angiotensin-aldosterone system (RAS) inhibitors or angiotensin-receptor neprilysin inhibitors, β-blockers (BB), mineralocorticoid-receptor antagonists (MRA), and sodium glucose cotransporter 2 (SGLT2) inhibitors. In addition to the effectiveness of each class of drug, the combined use of classes is more effective in improving the prognosis of HFrEF patients.2,3 Furthermore, uptitration (gradual dose increase) of GDMT is essential to avoid heart failure-related morbidity and mortality, especially during the vulnerable period that starts with hospital admission due to acute heart failure (AHF) and for the couple of months after.4,5
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However, despite the abundant evidence, many patients with HFrEF are not treated with adequate doses,6 particularly older HFrEF patients, and this is associated with decreased QOL. Barriers to optimizing GDMT include patient-related factors such as renal dysfunction, bradycardia, intolerance to medications, inadequate insurance coverage, and non-adherence. Clinical inertia, or the reluctance to change medications by either healthcare providers or patients or both, has been suggested as another significant factor in the implementation or not of GDMT.7 The fear of side effects from changing medication dosages in clinically stable patients can contribute to this inertia. However, strategies to address these factors and promote appropriate implementation and uptitration of GDMT should be considered to improve clinical outcomes.
In this issue of the Journal, Ohata et al8 report that only 17.1% of GDMT-eligible patients were uptitrated to maintenance doses, even with a relatively long hospital stay (median 18 days). They constructed a registry of AHF patients in 8 tertiary care hospitals in the Tokyo metropolitan area in Japan and analyzed 1,400 HFrEF patients hospitalized between 2018 and 2019. They defined maintenance doses for RAS inhibitors, BBs, and MRAs as approximately half or one-quarter of the maximum doses approved in Japan. SGLT2 inhibitors were not included because they were not approved for HFrEF usage at the time of the study. The authors also found that even though the target titrated doses were not full doses, the incidence of the primary outcome, which was a composite of 1-year all-cause death and HF rehospitalization rates after discharge, was significantly lower in patients who underwent uptitration than in those who did not. They found the factors affected with non-uptitration were older age and relatively low body mass index (Figure). Even after adjusting all potentially unbalanced and clinically significant covariates, the superiority of the titrated group over the nontitrated group remained almost the same. Furthermore, when focusing only on patients aged >65 years, the effectiveness of GDMT was suggested to be similar, although not significantly different. This result revealed that even in older patients, for whom uptitration of GDMT is challenging, the prognosis will be better if GDMT is initiated, and uptitration is performed as much as possible. The authors also evaluated the effectiveness of GDMT according to 3 clinical scenarios (CS; Figure). Achieving uptitration in CS1, where systolic blood pressure (SBP) is >140 mmHg, was significantly associated with a risk reduction of the primary outcome, but was not the case for CS2 (SBP 100–140 mmHg) or CS3 (SBP <100 mmHg). Although hypotension can be a challenge when implementing GDMT, it is not necessarily associated with a worse prognosis. Izumi et al reported that for HFrEF patients with lower blood pressure (SBP <100 mmHg), GDMT was associated with decreased adverse events (hazard ratio: 0.74, 95% confidence interval: 0.58–0.94).9 However, caution is warranted, particularly in patients with renal dysfunction, and each patient’s situation should be evaluated individually.
Factors associated with inadequate doses of GDMT and relative risk reduction with GDMT in different groups of HFrEF patient. The data for the Overall and Age >65 years groups are after propensity score matching with a 1 : 2 matching protocol of GDMT uptitrated and nontitrated patients with HFrEF. BMI, body mass index; CS, clinical scenario; GDMT, guideline-directed medical therapy.
Achieving GDMT in a multidisciplinary manner, including pharmacists or nurse practitioners and remote patient monitoring, is the goal for the future. Lynch et al reported that an interdisciplinary team consisting of a remote patient monitoring-home telehealth registered nurse, a cardiology licensed independent provider, and a clinical pharmacy specialist worked together to optimize GDMT for patients with HF, which led to a 25.3% increase in the optimization of GDMT doses and a potential reduction in HF admissions.10 All clinicians should consider the most effective way to achieve GDMT up-titration to improve the prognosis of the patients.
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