Implementation of medical therapy in different stages of heart failure with reduced ejection fraction

BackgroundReal-world evidence shows alarmingly suboptimal utilization of GDMT in HFrEF. One of the barriers of GDMT implementation appears to be concerns about the potential development of drug-related adverse events (AEs), particularly in high-risk patients. This study aimed to evaluate whether advanced HFrEF patients can be up-titrated safely and whether advanced HFrEF predisposes to the occurrence of putatively drug-related AEs. MethodsA total of 373 HFrEF patients from our prospective HF registry were analyzed for HF drug utilization and target dosages (TDs) at baseline, 2 months, and 12 months. Successful up-titration and AEs were evaluated for different stages of HF reflected by NT-proBNP (<1000pg/ml, 1000-2000pg/ml, >2000pg/ml). ResultsA stepwise increase in HF medications could be observed for all drug classes during follow-up. At 12 months 73%, 75%, 62%, 86% and 45% of patients received [&ge;]90% of TDs of beta-blockers (BB), renin-angiotensin system inhibitors (RASi), mineralocorticoid receptor antagonists (MRA), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and triple-therapy, respectively. Predictors of successful up-titration in logistic regression were baseline HF-drug TDs, eGFR, and potassium, but not NT-proBNP or age. The development of AEs was rare, with hyperkalemia as the most common event (34% at 12 months). AEs were comparable in all stages of HF. However, development of hyperkalemia was more frequent in patients with higher NT-proBNP and also accounted for most cases for incomplete up-titration. ConclusionsThis study suggests that with dedicated protocols and frequent visits GDMT can be successfully implemented across all stages of HFrEF, including patients with highest NT-proBNP levels who probably profit the most. CLINICAL PERSPECTIVEO_ST_ABSWhat is new?C_ST_ABSO_LIGDMT up-titration is feasible even in advanced HFrEF patients, with this study demonstrating that [&ge;]50% target doses for all HF medications can be achieved in about 90% of patients within 12 months through high-intensity care and frequent follow-up visits. C_LIO_LIAdverse events during up-titration are rare, even in high-risk patients, and the most notable AE, hyperkalemia, can be effectively managed in most cases without discontinuing therapy. C_LI What are the clinical implications?O_LIThis study demonstrates that GDMT up-titration is achievable even in advanced HFrEF, challenging the notion that medication intolerance should be part of the definition of advanced HF. C_LIO_LIPracticing physicians should pursue GDMT up-titration for all HFrEF patients, as AEs are manageable, and its potential benefit to stabilize disease progression and improve outcomes far outweigh the risks. C_LIO_LIThe lack of consensus on when to halt up-titration or define true intolerance, combined with limited evidence on GDMT efficacy or futility in advanced HF, underscores the need for further research to optimize treatment in this high-risk group. C_LI