‘No time to waste’: Implement guideline-recommended HF therapies simultaneously
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The benefits of HF medications are additive and incremental and provide similar benefits to patients with ischemic and nonischemic etiologies when initiated simultaneously, according to a speaker.
Despite treatment advances in HF, many eligible patients are not receiving one or more evidence-based, guideline-recommended HF therapies, Gregg C. Fonarow, MD, FACC, FAHA, FHFSA, director of the Ahmanson-UCLA Cardiomyopathy Center, co-director of the UCLA Preventive Cardiology Program, co-chief of the division of cardiology at UCLA and the Eliot Corday Chair in Cardiovascular Medicine and Science, said during a presentation at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. A serial, selective or drawn-out approach to HF treatment leads to delays, HF hospitalizations and deaths, which can be prevented with earlier use of guideline-directed medical therapy (GDMT), Fonarow said.
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“Mortality rates in HF remain phenomenally high with 377,000 deaths each year among patients with HF in the U.S.,” Fonarow said. “The deaths among HF patients represents about one in four of all cardiovascular deaths that will occur in the year in the U.S. The No. 1 reason Medicare-aged individuals are discharged from the hospital is for HF. Despite our therapeutic advances, the vast majority of patients are not on one or more of the evidence-based, guideline recommended lifesaving therapies. There is tremendous opportunity to improve the care and outcomes for this patient population.”
Cumulative benefits of GDMT
There are different trajectories in HF that each require different approaches, such as adults with new-onset HF or those with persistent or worsening HF, Fonarow said.
“All of these [trajectories] remain at substantially higher risk for death than other patients we encounter in clinical practice,” Fonarow said.
For patients with HF with reduced ejection fraction (HFrEF), the updated joint HF guideline from the American College of Cardiology, the American Heart Association and the Heart Failure Society of America recommends four classes of medications, including SGLT2 inhibitors; beta-blockers; mineralocorticoid receptor inhibitor antagonists (MRA); and renin-angiotensin-aldosterone inhibition with angiotensin receptor neprilysin inhibitors (ARNI), ACE inhibitors or angiotensin receptor blockers.
However, data from the U.S. CHAMP-HF registry (2016-2018) including 150 cardiology and multispecialty practices, demonstrate that use of ARNI and MRA therapies remain at 13% and 33%, respectively, despite such therapies being class I recommendations, Fonarow said. When medications were prescribed, few patients were receiving target doses of ACE inhibitors or angiotensin receptor blockers (17%), ARNIs (14%) and beta-blockers (28%), Fonarow said.
Among patients eligible for all classes of HF medication, just 1% were simultaneously receiving target doses of ACE/ARB/ARNI, beta blockers and MRA therapy, Fonarow said.
“Many clinicians must think if you get one or two drugs on board, then you are OK; that there is not much in the way of additive benefits; or that these drugs are subtractive or redundant,” Fonarow said. “Are we sure these therapies are truly additive?”
Data show there is no substantial overlap for the four key evidence-based therapies for HFrEF, Fonarow said. The optimal approach is to utilize each medication demonstrated to reduce all-cause mortality in combination, so long as not contraindicated or not tolerated — and to start without delay.
“If we look at how long this would take if we followed the historic sequence to the letter, it would be 28 to 56 weeks until GDMT was fully implemented,” Fonarow said. “Do we have the time? What is remarkable here is within days of initiation of each of these [medication] classes, there are clinical benefits seen in the Kaplan-Meier curves. Within 30 days, we see large, additive, cumulative benefits. There is no time to waste. Patients are harmed.”
Benefits of rapid therapy initiation
Simultaneous or very-rapid sequence initiation of the four pillars of GDMT offers several benefits for patients, including a substantial reduction in all-cause mortality risk, rapid improvements in EF and reductions in hospitalization and rehospitalization risk, Fonarow said.
Additionally, a simultaneous initiation of GDMT can also help to overcome clinical inertia and improve medication adherence, he said.
“When we draw therapy [initiation] out over time, one or more gets overlooked and patients are not treated,” Fonarow said.
For patients with HF with an EF or 40% or greater, new data from the EMPEROR-Preserved and DELIVER trials demonstrate the SGLT2 inhibitors empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly), and dapagliflozin (Farxiga, AstraZeneca) similarly reduce risk for CV death and HF hospitalization, with the benefit primarily driven by HF hospitalization, Fonarow said. Results were consistent regardless of type 2 diabetes status. SGLT2 inhibitors currently have a IIa recommendation for HFpEF in the guidelines, which were updated after the release of EMPEROR-Preserved but before the DELIVER findings were published.
“We can now begin to make the case that we have medical therapies, not as strong as for HFrEF, but therapies that can be considered for those with HF with mid-range and preserved HF,” Fonarow said. “SGLT2 inhibitors will most likely get a class I recommendation in upcoming guidelines, given the consistent benefits.”
Fonarow said it is a legitimate question to ask whether it is “truly worthwhile” for a patient taking on ACE inhibitor or angiotensin receptor blocker therapy to add on an SGLT2 inhibitor or MRA or “leave well enough alone.”
“For the average patient on an ACE inhibitor ... these extra steps would extend their survival by 6.3 years,” Fonarow said. “This is compelling evidence that we should work together to get all of these patients treated.
“These therapies provide high economic but most importantly high clinical value,” Fonarow said. “Importantly, we now have therapies for HF with mildly reduced and preserved EF, mainly the SGLT2 inhibitors, and in combination with other therapies, they can offer value.”
Reference:
- Anker SD, et al. N Engl J Med. 2022;doi:10.1056/NEJMoa2107038.
- Greene SJ, et al. J Am Coll Cardiol. 2018;doi:10.1016/j.jacc.2018.04.070.
- Heidenreich PA, et al. J Am Coll Cardiol. 2022;doi:10.1016/j.jacc.2021.12.012.
- Solomon SD, et al . N Engl J Med. 2022;doi:10.1056/NEJMoa2206286.
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Speaker. Session 7: Management of HF – 2022 Guidelines and Beyond. Presented at: World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease; Dec. 1-3, 2022; Universal City, California (hybrid meeting).
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