Start HFrEF therapies promptly: ‘Delayed initiation is lost benefit’
PHILADELPHIA — In patients with HF with reduced ejection fraction, the four pillars of optimal medical therapy should be started as soon as possible, a speaker said here.
“Delayed initiation is lost benefit,” Akshay S. Desai, MD, MPH, director of cardiomyopathy and heart failure in the advanced heart disease section of the cardiovascular division at Brigham and Women’s Hospital, said during a presentation at the Heart in Diabetes CME Conference.
Based on strong evidence, U.S. and European guidelines recommend that patients with HFrEF receive four classes of medication: beta-blockers, mineralocorticoid receptor antagonists, SGLT2 inhibitors and ACE inhibitors or angiotensin receptor-neprilysin inhibitors (preferably the latter), Desai said during the presentation.
In addition, he said, the guidelines recommend in-hospital initiation and rapid titration.
In a patient diagnosed with HFrEF at age 55 years, compared with initiating only a beta-blocker and an ACE inhibitor, initiating all four recommended drug classes prolongs life by 6.3 years, from 11.4 to 17.7 years, he said.
In particular, he said, SGLT2 inhibitors and angiotensin receptor-neprilysin inhibitors reduce CV events as early as 1 month after initiation.
Further, compared with initiating an ACE inhibitor or angiotensin receptor blocker first, initiating an SGLT2 inhibitor first reduces the probability of death at 1 year by 13.7 patients per 1,000 (from 65.3 patients per 1,000 to 51.6 patients per 1,000), he said.
There are different strategies for rapid initiation, including starting all four drug classes simultaneously, but the goal for all should be to “have four classes at 4 weeks” and to worry about uptitration after initiation.
Results from the STRONG-HF trial validated the guideline recommendations, he said. As Healio previously reported, in STRONG-HF, which was conducted before SGLT2 inhibitors became standard of care in HF, an intensive treatment strategy of rapid uptitration of appropriate medications and close follow-up reduced death and readmission at 180 days compared with usual care.
The results show “the true value of this rapid optimization strategy, which suggests that utilization of guideline-directed medical therapy in eligible patients across all the medication classes that were studied in this trial — this did not include SGLT2 inhibitors — increased to a greater extent in the intensive-therapy arm than in the control arm,” Desai said. “It was that difference in therapy, we think, not the touches for the patients, that drove the reductions in mortality and readmissions at 180 days.”
In-hospital initiation of the best therapies is particularly helpful, he said, citing the PIONEER-HF trial of the angiotensin receptor-neprilysin inhibitor sacubitril/valsartan (Entresto, Novartis) vs. enalapril and the EMPULSE trial of the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) vs. placebo. The ongoing DAPA ACT HF-TIMI 68 trial is studying the same phenomenon with the SGLT2 inhibitor dapagliflozin (Farxiga, AstraZeneca), he said.
“You must initiate early to gain the benefit” of the optimal medical therapy regimen, Desai said during the presentation. “You should consider simultaneous initiation, particularly of drugs with orthogonal side-effect profiles, rather than sequential initiation, to reduce the timeline. The hospitalized patients you see are at particularly high risk and they are a captive audience. You shouldn’t miss the opportunity to optimize therapy before they walk out the door.”
References:
- Heidenreich PA, et al. Circulation. 2022;doi:10.1161/CIR.0000000000001063.
- McDonagh TA, et al. Eur Heart J. 2021;doi:10.1093/eurheartj/ehab368.
- Mebazaa A, et al. Lancet. 2022;doi:10.1016/S0140-6736(22)02076-1.
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Desai AS, et al. Session 11 – Heart Failure – Prevention, Diagnosis and Management. Presented at: Heart in Diabetes CME Conference; June 9-11, 2023; Philadelphia.
