Slower and Lower Uptake of Novel Guideline-Directed Therapies for Heart Failure

In patients with HF, initiation of novel guideline-directed medical therapies to decrease mortality or rehospitalization lags behind therapies for other conditions.

In Japan, Sweden, and the United States (US), initiation of novel guideline-directed medical therapies (GDMTs) to reduce mortality or rehospitalization in patients with heart failure (HF) lags behind other GDMTs. These findings were published in JACC: Heart Failure.

The EVOLUTION HF (Utilization of Dapagliflozin and Other Guideline Directed Medical Therapies in Heart Failure Patients: A Multinational Observational Study Based on Secondary Data) study was a multinational, observational, longitudinal cohort study. Patient records from the Medical Data Vision claims registry (Japan), nationwide administrative registries (Sweden), and Optum deidentified Market Clarity Data (the US) were used to obtain information about GDMT use among patients with a hospitalization for HF. Novel GDMTs were defined as dapagliflozin, sacubitril, and valsartan.

A total of 266,589 patients initiated GDMT within 12 months of hospitalization for HF. In Japan, the most used GDMTs were β-blockers (n=68,798) and the least was dapagliflozin (n=7443). In Sweden the most common GDMTs were mineralocorticoid receptor antagonists (MRAs; n=14,315) and the least were sacubitril or valsartan (n=3854). In the US, β-blockers were the most frequently used GDMT (n=63,335) and dapagliflozin the least (n=1962).

In general, the most common comorbidities included atrial fibrillation, diabetes, kidney disease, and ischemic heart disease and patients with these comorbidities tended to be more likely to be given novel GDMTs.

In Japan, Sweden, and the US, initiation of novel GDMTs (dapagliflozin and sacubitril/valsartan in this study) after hospitalization for HF is markedly delayed compared with initiation of other GDMTs.

After the initial HF diagnosis, the median time to initiate novel GDMTs was 229 to 352 days compared with 13 to 34 days for other GDMTs in Japan, 347 to 212 days compared with 11 to 71 days in Sweden, and 938 to 679 days compared with 560 to 658 days in the US, respectively.

Similarly, the time to initiation of a novel GDMT following a recent HF hospitalization, either as a first GDMT or in addition to an existing regimen, was longer than for other GDMTs. Furthermore, fewer patients initiated dapagliflozin, sacubitril, or valsartan compared with other therapies in each country within 30 days after discharge.

When patients initiated novel GDMTs, they tended to already be using other GDMTs. For example, 80.0% to 96.5% of patients initiating sacubitril or valsartan were using β-blockers, 63.1% to 81.8% were using angiotensin-converting enzymes (ACE) inhibitors or angiotensin receptor blockers (ARBs), and 44.1% to 74.6% were using MRAs. Similar trends were observed for dapagliflozin.

In general, underdosing, slow uptitration, and early discontinuation were common trends observed for users of ACE inhibitors, ARBs, β-blockers, MRAs, and sacubitril or valsartan.

The results of this study may not be generalizable for other regions due to differing guidelines and drug approvals.

 “In Japan, Sweden, and the US, initiation of novel GDMTs (dapagliflozin and sacubitril/valsartan in this study) after hospitalization for HF is markedly delayed compared with initiation of other GDMTs,” the study authors wrote. “These results show an urgent need for earlier use of novel GDMTs to improve patient outcomes, particularly of dapagliflozin, which has been shown to reduce mortality in patients with HF.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Savarese G, Kishi T, Vardeny O, et al. Heart failure drug treatment—inertia, titration, and discontinuation: a multinational observational study (EVOLUTION HF). JACC Heart Fail. Published online, September 7, 2022. doi:10.1016/j.jchf.2022.08.009