Global Numbers Paint Grim Picture of GDMT Uptake, Costs, and HF Outcomes

A global look at the management and outcomes of heart failure (HF) patients discharged after a first hospitalization paints a grim picture, with investigators reporting a high risk of death in the first year, as well as very high costs of caring for this high-risk population.

Among patients participating in EVOLUTION HF, which includes those with a first-ever HF hospitalization in Japan, Sweden, the United Kingdom, and United States, there were 28.4 deaths and 13.6 readmissions for HF (per 100 patient-years of follow-up) in the year after a first hospitalization.

The study also revealed low rates of guideline-directed medical therapy (GDMT), with very few patients taking concomitant therapies indicated for HF, particularly heart failure with reduced ejection fraction (HFrEF). In the US and UK, for example, less than 3% were taking all four recommended drugs now recognized as foundational HF therapy.     

“Unfortunately, we are seeing huge gaps in the delivery of care,” lead investigator Biykem Bozkurt, MD, PhD (Baylor College of Medicine, Houston, TX), told TCTMD. “These patients have very high mortality rates. Out of these 260,000 patients, 28% died within the first year post-index hospitalization. What’s not recognized by the public is that heart failure is a deadly disease, sometimes even more severe than cancer. Time is of the essence.”

The four pillars of treatment— renin-angiotensin-aldosterone-system (RAAS) inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRAs), and SGLT2 inhibitors—change the disease trajectory and reduce the risk of cardiovascular death and heart failure hospitalizations. Unfortunately, in real-world practice, there isn’t the urgency to get patients started on GDMT following the index event, said Bozkurt.

“We may lose a significant proportion of our patients within a year or two,” she said. “The urgency of initiating and optimizing [heart failure] therapies should be very similar to cancer. We wouldn’t delay therapy in cancer for years.

Adam DeVore, MD (Duke Clinical Research Institute, Durham, NC), who wasn’t involved in the study, said the findings—specifically the high rate of readmissions and mortality, as well as low uptake of GDMT—are disappointing, if unsurprising.

“Sadly, we had hoped that things would get better as therapies have improved over time, but the most striking thing about this study is that it’s very contemporary and the numbers don’t look a lot better,” he told TCTMD. “The other part of this, and I’ve been in involved in CHAMP-HF, which is very US-centric, is that when we try to figure out why these numbers are so poor, we tend to focus on the healthcare system, but these numbers show they are poor across a lot of different health systems.”

Japan, Sweden, UK, and US

Published this week in JACC: Heart Failure, EVOLUTION-HF is an observational, longitudinal cohort study using data extracted from electronic health records (EHRs) or claims data. Patients were included in the study if they had a first-ever inpatient HF hospitalization between 2018 and 2022.

As part of the study, researchers assessed clinical outcomes and hospital healthcare costs of a first HF hospitalization in cohort 1 and documented the use of contemporary GDMT after hospital discharge in cohort 2. The first cohort spanned 2018 to 2020 and allowed researchers sufficient follow-up to avoid potential influences of the COVID-19 pandemic. In cohort 2, which spanned 2020 to 2022, researchers wanted to evaluate the uptake of the newest drug class, SGLT2 inhibitors, approved in many countries in 2020 for the treatment of HFrEF.

It’s an opportunity that is lost. Biykem Bozkurt

The most-frequent clinical event was all-cause rehospitalization, with 96.8 events per 100 patient-years. Regarding mortality, which was tracked in Sweden and the UK only, there were 28.4 and 16.2 all-cause and cardiovascular deaths per 100 person-years, respectively. Additionally, there were 13.6 rehospitalizations for HF and 4.5 rehospitalizations for CKD per 100 patient-years, respectively. Event rates were “generally similar” across all countries, say investigators.

In the 12 months after discharge for the first HF event, subsequent HF and CKD care was responsible for the largest cumulative healthcare costs in all four regions. These healthcare costs exceeded those for atherosclerotic cardiovascular events in all countries, say investigators. In US dollars, costs of care over the 12 months after hospital discharge ranged from $6,000 in Japan to $14,000 in the US, substantially more than the costs of caring for CKD, MI, stroke, and peripheral artery disease across all four countries studied.

Regarding medication use, initiation of RAAS inhibitors and beta-blockers within 3 months of hospital discharge ranged from 60% to 80% across the four regions, uptake that remained relatively unchanged across the study period. Similarly, use of MRAs was approximately 20% to 40% in the 3 months after discharge and changed little over time, except in Sweden, where usage increased. Use of the angiotensin-receptor neprilysin inhibitor (ARNI) sacubitril/valsartan (Entresto, Novartis) after discharge was also low at less than 10%, and its use didn’t change over time. SGLT2 inhibitors were started in 2% to 11% of patients at 3 months in first quarter after the drugs were approved, but the rate increased to 8% to 35% over time.

At the end of the study period, concomitant use of GDMT remained low. For example, just 10% and 21% of patients in Japan and Sweden, respectively, were taking four medications recommended by the guidelines. In the UK and US, the situation was bleaker:  just 2% and 3%, respectively, were taking four GDMTs for HF. Over time, there was an increase in the percentage of patients taking two or three concurrent medications, though.

To TCTMD, Bozkurt said that first-line quadruple therapy fits the mold of “induction therapy,” like chemotherapy in cancer, with add-on medications used as consolidation therapies. In general, “the proportion of patients using all four heart failure medications is low, very low, even in the best circumstances,” she said. “It’s an opportunity that is lost.”

She added that there are multiple diseases, including ischemic heart disease, that rely on multiple medications, but strategies in those settings aren’t perceived as “prohibitive or too complex” because the effect on clinical outcomes is recognized. “In heart failure, we need to recognize quadruple therapy, or multiple medications, as standard therapy,” said Bozkurt.

Recipe for Improvement

Like Bozkurt, DeVore believes the bleak outcomes after an index hospitalization for HF can be blunted if more patients get onto GDMT earlier in their disease. “In general, there’s been a movement to keep people in the hospital a little bit longer and to start those medications earlier, to get them on medicines before they leave,” he said. “It’s an important time to observe how people respond because they’re being monitored.”

Implementation science, addressing the best ways to start and maintain patients on GDMT, is an active but challenging area of research. In the PROMPT-AHF study, for example, the use of targeted alerts in  the EHR didn’t increase the number of patients sent home on GDMT. Similarly, the PACT-HF recently failed to show any differences in GDMT uptake with a novel strategy of discharging patients to a transitional, multidisciplinary care team. In the CONNECT-HF study, which was led by DeVore, researchers found that use of a digital, app-based intervention led to an improvement in a composite score tracking HF quality-of-care metrics, but the main trial found no improvement in clinical outcomes or quality of life.

The current US guidelines for HFrEF recommend physicians initiate and optimize GDMT in the hospital once the patient is stabilized but before discharge. “Whether it’s all four medications, or one, two, or three, will depend on the patient,” said Bozkurt, but trying to initiate and optimize GDMT after discharge with traditional follow-up visits over 3 or 6 months would inevitably delay care. She hopes that widespread recognition of the need for multiple medications among HF specialists, cardiologists, and even general practitioners will help improve uptake.

DeVore, likewise, said that early window after a first-ever HF hospitalization is an ideal time to get patients on GDMT. While there are limited data to support the use of all four GDMTs after new-onset HFrEF requiring hospitalization, the very poor outcomes in the first year observed in EVOLUTION HF warrant getting patients treated sooner rather than later, he said.

In the paper, Bozkurt and colleagues point out that information about left ventricular ejection fraction was not available for the majority of patients included in EVOLUTION HF. As a result, they can’t know if physician prescribing adhered to the guidelines.

Still, even if a substantial proportion of patients in the study had heart failure with preserved or midrange EF, both of which have weaker recommendations for multiple GDMTs than do HFrEF, “the low rates of uptake for all four GDMTs underline the need for further optimization of implementation strategies,” they write.