Treat Heart Failure More Like Cancer

Early intensive uptitration of neurohormonal blockade therapy in patients with acute heart failure improves congestion and reduces longer term negative outcomes, a new analysis of the STRONG-HF trial suggested.

Jan Biegus, lead author of the study from the Institute of Heart Diseases in Wroclaw, Poland, said in an interview that the results will start to change the perception of how to treat the congestion of acute heart failure. He compared the new approach to induction chemotherapy for cancer — hitting the disease hard as soon as possible to get the best results.

The STRONG-HF trial treated 1078 patients hospitalized for acute heart failure with either early and rapid uptitration of neurohormonal blockade including renin-angiotensin-aldosterone system inhibitors and beta-blockers or standard diuretic therapy. The main finding was that the early uptitration strategy reduced the 6-month risk for death or heart failure readmission by one third.

Now, a new analysis published in Journal of the American College of Cardiology, has found that in addition to this benefit, early uptitration of neurohormonal blockade therapies has the added advantage of reducing congestion.

Biegus said doctors have been wary of going in early and aggressively with neurohormonal drugs because there has been a feeling that patients need to be completely decongested before starting to uptitrate neurohormonal blockers. “But now we can see that uptitrating these drugs early is safe and effective, and we can get decongestion for free,” he said.

Uptitrating Fast

In the study at baseline, the same proportion of patients in both arms had successful decongestion (46-48%). But after 90 days, 75% of the high-intensity group achieved successful decongestion vs 68% of the standard care group, and the high-intensity group had a significantly better chance of sustaining decongestion at day 90.

Each separate component of the congestion score was significantly better in the high intensity group, and additional markers of decongestion also favored the high intensity approach, including weight reduction, N-terminal pro–B-type natriuretic peptide level, and lower orthopnea severity. This was achieved despite a lower mean daily dose of loop diuretics at day 90 in the high-intensity arm.

Successful decongestion in all individuals was associated with a lower risk for 180-day heart failure readmission or all-cause death.

Biegus said these results should challenge the diuretic-only approach to treating heart failure. “Physicians like to increase diuretics to treat congestion in acute heart failure, but this does not improve outcomes,” he said. “We have shown here that increasing neurohormonal blockade therapy early can reduce congestion. We already know that it improves longer term outcomes, so this is a double win.”

While diuretics relieve symptoms, they do not target key pathophysiological processes underlying the development of congestion in acute heart failure, explained the researchers.

A Challenge to the Diuretic-Only Approach

Neurohormonal blockade directly disrupts the fundamental mechanisms contributing to congestion, such as overactivation of the renin-angiotensin-aldosterone and sympathetic nervous systems, which leads to vasoconstriction and sodium and water retention.

Biegus said the new findings do not rule out using diuretics. “There is room for both,” he added. “Diuretics are needed in the beginning in patients with fluid overload. But once a patient is no longer in fluid overload, our data suggest that the best option is to increase neurohormonal blockade therapy, which will allow us to reduce the dose of diuretics.”

Biegus said the results of this trial support a much more aggressive approach to treating heart failure.

“Everyone is afraid of cancer because it is a deadly disease,” he said. “In general, the treatment approach is to go in aggressively at the beginning to give the patient the best chance. We realize that there may be side-effects of therapy, but we accept that these are often justified to achieve better outcomes.”

He says a similar approach should be taken in heart failure. “This is also a deadly disease, but in heart failure we are afraid of side-effects, and we are very gentle in our approach to treatment,” he said. “Our data show we need to be more aggressive, and like for cancer, we need to hit heart failure earlier and harder for better results.”

In an editorial accompanying the publication, Biykem Bozkurt, MD, and Ajith Nair, MD, from Baylor College of Medicine in Houston supported the idea of pivoting from symptom relief to addressing underlying pathologic mechanisms by initiating and titrating guideline-directed medical therapy after hospitalization.

“Without a strategy to alter disease trajectory through initiating and optimizing guideline-directed medical therapy during and after hospitalization, achieving decongestion alone may be inadequate for discharge,” they noted.

Although some patients may require slower uptitration due to hypotension, bradycardia, hyperkalemia, renal dysfunction, and other factors, “overall, the results of the STRONG-HF analysis provide compelling evidence for a shift toward more proactive and intensive use of neurohormonal blockade,” they add. “Early and intensive uptitration of guideline-directed medical therapies can lead to sustainable clinical benefits and improved outcomes.”