Initiating guideline-recommended medical therapy (GRMT) in patients with heart failure with reduced ejection fraction (HFrEF) quickly after diagnosis is feasible in a real-world setting, according to findings from the ongoing TITRATE-HF registry published April 24 in the European Heart Journal.

Conducted in 48 hospitals in The Netherlands, Jishnu Malgie, et al., examined the time to initiating GRMT, dose adjustments, discontinuations and the reasons for changes from the time HFrEF was diagnosed to six months in 1,508 de novo HFrEF patients between June 2022 and February 2024. Their median age was 70 years, 31% were women and median LVEF was 30%.

Results showed that at six weeks, 46% of patients were on quadruple therapy, consisting of renin-angiotensin system inhibitors (RASis), beta-blockers, mineralocorticoid receptor antagonists (MRAs) and SGLT2 inhibitors. RASis and beta-blockers were most commonly the first drugs used, followed by MRAs and then SGLT2 inhibitors. After 180 days, 84% of patients continued quadruple therapy.

Additionally, at six months, 66% of patients were prescribed quadruple therapy, but only 1.3% achieved target doses for all four drugs. While drug titrations were frequent in the first 60 days, the authors note this is largely due to physicians accepting suboptimal doses, with only about 20-37% of cases due to side effects. Furthermore, the rate of discontinuing each class of drug was low, about 9-13%, but rechallenging the drug classes was successful in about 83% of patients.

Among the barriers to implementing GRMT were blood pressure management and worsening renal function, according to a survey of registry investigators. Another problem, according to 49% of survey participants, was that HF clinics were not prepared to handle the time needed for optimal GRMT implementation and titration.

"The TITRATE-HF study demonstrates that rapid initiation of GRMT for HFrEF is feasible in real-world clinical practice. Nonetheless, our results highlight the urgency for a proactive approach and ongoing dose titration of pharmacological therapy beyond the initial first months to fully optimize treatment," the authors write.

In an accompanying editorial comment, Kieran F. Docherty, MB ChB, Li Shen, MBBS, PhD, FACC, and John J. V. McMurray, MD, FACC, write, "We are still starting combination therapy too slowly – if 66% of patients can tolerate quadruple therapy by six months, most can probably tolerate this by four weeks." They note each GRMT drug has a rapid onset of benefit, and that delaying their use can lead to avoidable deaths and hospital admissions.

"The better rate of prescription in hospitalized patients points to process rather than patient factors in this shortfall," and they highlight that "the lack of time and resources in outpatient clinics to handle the demands of rapid sequencing" was one of the main barriers to the implementation of therapy identified by clinicians.