Treatment strategy for heart failure patients with guideline-directed medical therapy intolerance: a real-world prospective study

Abstract Background Guideline-directed medical therapy (GDMT) reduces the incidence of worsening events in patients with heart failure (HF) with reduced ejection fraction (HFrEF). However, in actual clinical practice, a proportion of patients are unable to tolerate complete GDMT. Purpose This study aimed to assess the medication strategy for patients with HFrEF who are intolerant to GDMT. Methods A total of 110 patients admitted with acute HF were included in the study. The patients were non-randomly assigned to receive complete or incomplete GDMT after assessment by doctors before discharge from the hospital. All patients were followed up for 180 days. The primary composite endpoint was worsening HF-associated events, including death or rehospitalization due to HF, and the need for intravenous diuretic therapy. The secondary endpoints were the New York Heart Association functional class, blood pressure, and cardiac structure and function assessed by echocardiography. Results The main reasons for GDMT intolerance were renal insufficiency (41.8%) and hypotension (26.4%). GDMT-intolerant patients had lower eGFR (50.4 ml/min/1.73 m² vs. 70.9 ml/min/1.73 m²; p=0.002) compared with those who tolerated GDMT, and included more patients with chronic kidney disease (56.4% vs. 23.6%, p<0.001) and higher NT-proBNP levels (5340 pg/ml vs 8080 pg/ml, p=0.039) at baseline. While patient mortality was similar between the two groups, the rate of worsening HF events was lower in patients with GDMT (hazard ratio: 0.736; 95% confidence interval: 0.389−1.393) and vericiguat treatment (p<0.001). In terms of the secondary endpoint, patients who received GDMT showed greater improvements in cardiac structure and function although there was no statistical difference between the groups. In the prespecified subgroup analysis of the effects of vericiguat on the primary endpoint, the incidence of worsening HF events was reduced by vericiguat, regardless of whether the patient was comorbid with GDMT or not, or whether they had a previous history of HF (p-interaction= 0.519 and 0.227, respectively). Conclusions Patients with early in-hospital initiation of complete GDMT and continuous GDMT after discharge had better outcomes compared with patients who were intolerant to GDMT. Co-administration of vericiguat with or without GDMT may reduce the incidence of worsening HF events in HF patients within 180 days.Results of the primary endpoint