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Even with the introduction of newer, better-tolerated medications, the slow and rocky implementation of guideline-directed medical therapies (GDMTs) for heart failure (HF) has remained a global issue, a study found.

Among Americans who were new users of any GDMT drug class after HF hospitalization, those initiating dapagliflozin (Farxiga) and sacubitril/valsartan (Entresto) had waited 33 and 19 days, respectively, in comparison with the 18-24 days for older GDMTs. The difference was similar in Japanese and Swedish registries, according to Gianluigi Savarese, MD, PhD, of Karolinska University Hospital in Stockholm, Sweden, and collaborators of the EVOLUTION HF study.

Moreover, the proportion of people initiating dapagliflozin or sacubitril/valsartan by day 30 after discharge reached 37.3% and 62.0% in the U.S., 74.6% and 72.7% in Japan, and 54.9% and 59.5% in Sweden, Savarese's group reported in a paper published in .

"Despite the paradigm-shifting trial results for novel GDMTs, early initiation of novel GDMTs in real-world settings remains a clinical challenge," the authors wrote. "However, SGLT2 inhibitors have entered clinical guidelines only recently, and changes in treatment strategies may improve over time."

"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," the team concluded.

Dapagliflozin was the only SGLT2 inhibitor considered in the study, which captured GDMT uptake starting from the first full calendar month after dapagliflozin's approval for HF across the three countries: Japan (December 2020), Sweden (December 2020), and the U.S. (June 2020).

SGLT2 inhibitor therapy has been shown to safely treat HF patients across the spectrum of ejection fraction and is associated with better ease of use, compared with other GDMTs, given its once-daily dosing and lack of need for titration.

Indeed, Savarese's team reported that when pooled across countries, the proportion of HF patients discontinuing dapagliflozin within 12 months was a relatively low 23.5%, with over three-quarters of people meeting their full target dose.

Rates of discontinuation and target dose misses were about the same or higher with sacubitril/valsartan and other GDMTs, namely angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists.

The present study is the latest of many reports to describe the poor uptake of GDMTs for HF. It may appear that the Japanese and the Swedes do a better job than the Americans, but the issues are apparent across these countries, commented Tariq Ahmad, MD, MPH, of Yale School of Medicine in New Haven, Connecticut.

"This is basically showing again that there is a huge lag between availability of data and its translation at the bedside," Ahmad said in an interview. "The majority of people are not practicing the best evidence-based medicine and are probably not reading these papers. We need a behavioral economics approach to why the gap seems to be bigger in heart failure than some other cardiology specialties."

He said he suspected the main barriers to better GDMT implementation are inertia, paperwork and cost, and lack of knowledge among the non-HF specialists, who treat the majority of HF patients. "There's a lack of consensus among the general medicine physicians on starting these medications. That is a big issue," he said.

At Yale, Ahmad's group was able to boost GDMT uptake using a clinical decision-support intervention in the PROMPT-HF trial. Outpatient clinicians were alerted every time they accessed the electronic health record of an HF outpatient not on one of four GDMT medication classes, and were given individualized guidance on prescribing GDMT. "The improvement was not dramatic," he acknowledged.

"While the discovery of novel therapies is exhilarating, we must spend an equal amount of attention and focus on understanding what the barriers are to getting patients on these medications and then direct our energies to mitigating those barriers," said Anu Lala, MD, of Mount Sinai Health System in New York City, who was not involved in EVOLUTION HF.

This had relied on Japan's Medical Data Vision claims registry, Sweden's nationwide administrative registries, and the U.S. Optum de-identified Market Clarity database.

Out of over three million people in those three countries, investigators identified 266,589 people initiating any GDMT drug class within 12 months of an HF hospitalization discharge who had sufficient data.

Across the board, patients initiating dapagliflozin or sacubitril/valsartan tended to be younger and less likely female than those starting other drug classes.

Savarese and colleagues warned, however, that their dataset lacked key information such as ejection fraction data.

"These data add to the growing body of evidence representing the need for implementation of our guideline-directed therapies that we know save lives and decrease hospitalizations," Lala maintained.

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