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Starting heart failure medications before heading home from an acute heart failure hospitalization and rapid up-titration afterward safely improved outcomes across heart failure categories, the STRONG-HF trial showed.

The high-intensity care intervention reduced 180-day heart failure readmission or death from any cause by a relative 34% compared with usual care (15.2% vs 23.3%, P=0.0021, risk ratio 0.66, 95% CI 0.50-0.86).

More overall adverse events were recorded in the group with more frequent healthcare visits, but serious and fatal events were similar between strategies, reported Alexandre Mebazaa, MD, of Hôpital Saint-Louis Lariboisière in Paris.

Intensive early managment "was readily accepted by patients," despite the close follow-up and more frequent care visits, because it reduced symptoms and improved quality of life as well, Mebazaa reported at the American Heart Association annual meeting in Chicago.

"Most treatments that were used as part of the high-intensity care strategy in the STRONG-HF study are widely available, and, for the most part, they are generic drugs," the group noted in the paper published simultaneously in . "Hence, the implementation of the results of the STRONG-HF study could be easily and rapidly achieved globally, and not restricted in countries and regions where newer expensive medications are not widely available."

Notably, subgroup analysis suggested a benefit across left ventricular ejection fraction (LVEF) categories, with no significant interaction. However, the point estimate for benefit of the intervention was numerically more favorable for the preserved ejection fraction (HFpEF) group: 12.5 percentage point risk difference for the third of patients with an LVEF over 40% versus 6.3 percentage points in those with a lower EF.

"Probably for the first time, we could show that patients with a preserved ejection fraction had very preserved benefits of the high-intensity care arm," Mebazaa said at an AHA press conference that included the trial.

HFpEF is not usually expected to benefit from rapid up-titration of beta-blockers, noted session panelist Amanda Vest, MBBS, MPH, of Tufts Medical Center in Boston.

"It's a good surprise, I would say," said Mebazaa. While further analysis by LVEF is pending, he noted that for the small number of patients with LVEF over 50%, the results were "impressive, and apparently it works."

Implications

However, Mebazaa acknowledged at the late-breaking clinical trial session: "The next challenge is the rapid education to implement the STRONG-HF technique into daily practice."

The findings "call for a more algorithmic approach to diagnosis and therapy ... now having guardrails in a more defined approach to manage patients consistently," commented Martin Leon, MD, of Columbia University Irving Medical Center/NewYork-Presbyterian Hospital in New York City and moderator of the press conference.

"How do we do this right?" posited Julia Indik, MD, PhD, of the University of Arizona College of Medicine in Tuscon and study discussant for the trial at the press conference.

"Boy, do we need staff," she said. "We need clinical providers, we need nurse practitioners, we need boots on the ground to get these patients in and carry out these important strategies. We are plagued by staffing shortages, all the more so after the COVID pandemic. We have to educate our cardiologists on best practices. And we still don't know -- we think it's going to be very cost-effective but that needs to be shown."

The trial used largely cardiologists and heart failure specialists to carry out the intervention, Mebazaa said.

"After acute heart failure, although it's known to be associated with very frequent readmission, very few patients are monitored after discharge and treated with full-dose heart failure therapies," Mebazaa noted.

Both U.S. and European guidelines recommend follow-up with patients within 4 weeks after discharge, but with a low level of evidence.

Trial Details

The trial included 1,078 patients ages 18 to 85 (mean 63, 39% women, 77% white) who had been admitted to 87 hospitals in 14 countries due to acute heart failure that was not treated with full doses of guideline-directed drug treatment and who had an NT-proBNP level over 1,500 pg/mL. Patients were randomly assigned to open-label usual care, in which adjustment and initiation of therapy was by usual practice, or to high-intensity care.

In the high-intensity arm, patients were prescribed half of the optimal dose of either an ACE inhibitor, angiotensin receptor blocker, or angiotensin receptor/neprilysin inhibitor (ARNI) along with a half dose of a beta-blocker and a half dose of a mineralocorticoid receptor antagonist (MRA). One week after discharge, patients had a safety visit that included a clinical exam and biomarker check on NT-proBNP, potassium, creatinine, and hemoglobin. The following week, the three drugs were up-titrated to full doses if patients remained fine. Subsequent safety visits were provided at weeks 3 and 6. The primary endpoint was assessed at 180 days with a phone call to assess outcomes.

The trial was stopped early for efficacy at the end of September.

As expected, the intensive management group got to full drug doses more often: 55% versus 2% for renin-angiotensin blockers, 49% versus 4% for beta-blockers, and 84% versus 46% for MRAs. And not surprisingly, all measures of congestion -- blood pressure, pulse, New York Heart Association class, body weight, and NT-proBNP concentration -- had decreased more by day 90 with the intervention.

For the main secondary endpoint, quality of life on the 5-point EuroQol-5D visual analog scale was 3.5 points better with the high-intensity strategy than with usual care at day 90 (P<0.0001).

As to what proportion of the effect of the intervention in altering the prognosis of these patients in the vulnerable early post-discharge period was due to extra healthcare attention versus pharmacologic effects, Mebazaa's group noted:

"The effect of more intense management (i.e., more visits) early after admission to hospital for an acute heart failure by itself (i.e., without up-titration) has been examined in four previous reasonably sized and powered prospective randomised studies. In all these studies, no effect was seen for intensified follow-up alone on endpoints of readmission or death. Therefore, without rapid up-titration to maximally tolerated doses, additional early follow-up visits alone do not seem to affect patient outcomes," the authors wrote.

The higher number of non-serious adverse events likely was related to the higher number of visits with more intensive versus usual care, Mebazaa said.

were not used in many patients, as has been the case in clinical practice, Mebazaa noted, and the trial was largely done before SGLT2 inhibitors were recommended for wide use in heart failure guidelines.

"The reason we did this trial was because cardiologists were reluctant to use the three first major therapies," he said at the press conference. "SGLT2 are known to be safe drugs -- at least much safer than three others -- but indeed it has to be proven."

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