It’s as if hospitals, clinicians, and the health care system itself were unprepared for such success as a powerful multiple-drug regimen emerged for hospitalized patients with heart failure with reduced ejection fraction (HFrEF).
Uptake in practice has been sluggish for the management strategy driven by a quartet of medications, each with its own mechanisms of action, started in the hospital simultaneously or in rapid succession over a few days. Key to the regimen, dosages are at least partly uptitrated in the hospital then optimized during close postdischarge follow-up.
The so-called four pillars of medical therapy for HFrEF, defined by a left ventricular ejection fraction (LVEF) of 40% or lower, include an SGLT2 inhibitor, a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a renin-angiotensin-system (RAS) inhibitor – preferably sacubitril-valsartan (Entresto) or, as a backup, an ACE inhibitor or angiotensin receptor blocker (ARB).
Academic consensus on the strategy is strong. The approach is consistent with heart failure (HF) guidelines on both sides of the Atlantic and is backed by solid trial evidence suggesting striking improvements in survival, readmission risk, and quality of life.
Gregg C. Fonarow, MD, University of California, Los Angeles, said in an interview.
“Yet, when we look at their actual implementation in clinical practice, we’ve seen this slow and variable uptake.”
So, why is that?
The STRONG-HF trial tested a version of the multiple-drug strategy and demonstrated what it could achieve even without a contribution from SGLT2 inhibitors, which weren’t yet indicated for HF. Eligibility for the trial, with more than 1,000 patients, wasn’t dependent on their LVEF.
Patients assigned to early and rapidly sequential initiation of a beta-blocker, an MRA, and a RAS inhibitor, compared with a standard-care control group, benefited with a 34% drop (P = .002) in risk for death or HF readmission over the next 6 months.
Few doubt – and the bulk of evidence suggests – that adding an SGLT2 inhibitor to round out the four-pillar strategy would safely boost its clinical potential in HFrEF.
The strategy’s smooth adoption in practice likely has multiple confounders that include clinical inertia, perceptions of HF medical management as a long-term outpatient process, and the onerous and Kafkaesque systems of care and reimbursement in the United States.
For example, the drug initiation and uptitration process may seem too complex for integration into slow-to-change hospital practices. And there could be a misguided sense that the regimen and follow-up must abide by the same exacting detail and standards set forth in, for example, the STRONG-HF protocol.
But starting hospitalized patients with HFrEF on the quartet of drugs and optimizing their dosages in hospital and after discharge can be simpler and more straightforward than that, Dr. Fonarow and other experts explain.
The academic community’s buy-in is a first step, but broader acceptance is frustrated by an “overwhelming culture of clinical care for heart failure” that encourages a more drawn-out process for adding medications, said Stephen J. Greene, MD, Duke Clinical Research Institute, Durham, N.C. “We need to turn our thinking on its head about heart failure in clinical practice.”
The “dramatic” underuse of the four pillars in the hospital stems in part from “outmoded” treatment algorithms that clinicians are following, Dr. Fonarow said. And they have “no sense of urgency,” sometimes wrongly believing “that it takes months for these medications to ultimately kick in.”
For hospitalized patients with HFrEF, “there is an imperative to overcome these timid algorithms and timid thinking,” he said. They should be on “full quadruple therapy” before discharge.
“And for newly diagnosed outpatients, you should essentially give yourself 7 days to get these drugs on board,” he added, either simultaneously or in “very rapid sequence.”
What’s needed is a “cultural shift” in medicine that “elevates heart failure to the same level of urgency that we have in the care of some other disease states,” agreed Muthiah Vaduganathan, MD, MPH, Brigham and Women’s Hospital and Harvard Medical School, Boston.