Rethinking the Evidence for ICDs for HFrEF in Light of Today’s GDMT

Improvements in optimal medical therapy for patients with heart failure with reduced ejection fraction (HFrEF) have helped reduce the risk of sudden cardiac death (SCD)—in the modern era, though, just how much an implantable cardioverter-defibrillator (ICD) can add to that protection is less clear. A new review article offers some food for thought.

“We're living in a day and time where we have a lot of options for patients with heart failure that can improve their survival and quality of life,” Amin Yehya, MD (Sentara Heart Hospital, Norfolk, VA), the paper’s lead author, told TCTMD. “Going back 20 years ago or more when the early ICD trials were conducted and the recommendations were [issued], medical therapy was completely different. Most of those patients in those trials were not on optimal dosages of medical therapy and they were not on contemporary guideline-directed medical therapy.”

Thanks to practice-changing trials over the last decade, guidelines for HFrEF now emphasize rapid initiation of four key classes of medical therapy—an angiotensin receptor-neprilysin inhibitor (ARNI), a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a sodium-glucose cotransporter 2 (SGLT2) inhibitor.

But it’s no easy task, with study after study showing that most patients who are eligible for foundational GDMT don’t receive it. Clinical inertia is often cited, but so too is the inability of real-world patients to tolerate optimal medication doses in the same way as clinical trial participants. Yehya and colleagues note that likely due to this reason, the absolute rates of all-cause death, CV death, and SCD remain two- to fivefold higher in population, community, registry, and real-world studies compared with trials.

“We need to make sure our patients are on optimal dosages of these medications, if they can tolerate them, because these medications work [and can] significantly improve survival, improve ejection fraction, and reduce risk of sudden cardiac death. And that by itself can sometimes mitigate the need for an ICD,” Yehya added.

Used in the right type of patient, ICDs can confer a survival benefit for some HFrEF patients, but the review paper, published December 4, 2024, in JACC: Heart Failure, emphasizes the importance of accounting for numerous patient characteristics, including frailty and dementia, when considering ICD placement.

“ICD therapies are not benign. They are prone to complications and . . . there can be the risk of the procedure itself, so what we tried to do in this paper is take a deep dive [to understand] who can benefit from ICDs to prevent inappropriate ICD implantation,” Yehya said. “Shared decision-making should be an integral part of all our discussions with patients. We have to educate them. We have to make sure that they understand the therapy . . . and understand the other options and the consequences of whatever option they do choose.”

Yehya and colleagues also stress the importance of considering how patients’ wishes may evolve over time as their disease and symptoms worsen. Revisiting ICD discussions as patient age is key.

Disparities and Ongoing Questions

In the landmark trials that cemented the role for ICDs, including MADEIT, MUSTT, and DANISH, women and nonwhite patients were significantly underrepresented. Even today, Yehya and colleagues note, Black patients are less likely to seek medical care at centers with the resources and infrastructure necessary for the effective implementation of ICDs and may face other challenges related to insurance, health literacy, transportation, and more.

Sex-based gaps also are entrenched. “While reasons for sex disparities in the use of ICD therapy remain inadequately explored, possible explanations include physician bias rooted in the predominantly male composition of major ICD trials,” they write.

For all those reasons, they point to the need for additional research focused on sex-specific and socioeconomic factors, including neighborhood deprivation index and cultural considerations to better understand how to break down barriers to ICD use in these populations while also ensuring optimal GDMT.

Even with the strides that have been made with medical therapy, patients with HFrEF still face residual risks, which were reported to be as high as 9.2% in DAPA-HF and 10% in EMPEROR-Reduced for the endpoint of CV death. Data like these raise the question of how much residual risk still warrants protection with an ICD for certain patients. Yehya and colleagues say this is where it is important to carefully evaluate competing risks and incorporate clinical assessments and testing as part of shared decision-making and long-term risk assessment.

Another outstanding question that is not easily answered is how to identify patients who would benefit from an ICD based on findings other than an LVEF of ≤ 35%. Yehya et al say there is urgent need to define phenotypes in this area.

Timing of ICD placement is another important question that many clinicians may have and a section of the review article offers scenarios to consider in this regard.

“Many times when patients come into heart failure specialists they are not in a good situation. They may have had multiple hospitalizations [and] need advanced heart failure care,” Yehya said. “That's why it's important to have early referrals to heart failure physicians and specialized cardiologists who can help in managing these patients. We want to make sure patients first of all are receiving the medical therapy that can improve their survival [and] get the earliest possible care when they still have options and we can manage their risk appropriately.”