STRONG HF: More Beats Less After Discharge for Heart Failure

John M. Mandrola, MD


November 08, 2022

Everyone agrees that getting patients with heart failure on optimal doses of medications leads to better outcomes. We agree because clinical trials consistently find additive benefit of each class of these drugs.

The problem is that in real-world practice, there are no run-in periods to select patients who can tolerate the drugs, there are no research nurses who coordinate follow-up, and few patients have the motivation or resources to volunteer to be in a trial.

These realities have led practicing doctors to be cautious in their uptitration of heart failure meds. Some experts feel this caution causes widespread undertreatment and worse outcomes.

At the American Heart Association (AHA) Scientific Sessions 2022, the primary investigator of the STRONG-HF trial, Alexandre Mebazaa, MD, showed us that there is a way to accomplish maximal medical therapy in patients discharged after an episode of acute heart failure—and it led to better outcomes.

The answer was simple: more, not, less care. A lot more.


STRONG HF enrolled about 1600 patients with acute heart failure who were not treated with optimal medications from 87 hospitals in 14 countries. Nearly 90% were recruited from Africa and Russia. Patients were randomly assigned to a high-intensity treatment arm or usual care.

The high-intensity arm was aptly named. Patients first were given half the optimal dose of heart failure meds while still hospitalized. These included renin-angiotensin blockers, β-blockers, and mineralocorticoid receptor antagonists. At week 1 after discharge, patients were checked for tolerance of these meds. At week 2, meds were uptitrated to full dose. The week 3 visit was used to check tolerance of full-dose meds, and then patients were checked again after 6 weeks. Notably, cardiologists performed these "safety" visits, using only a history, exam, and measurement of basic labs.

The primary endpoint of readmission for heart failure or all-cause death was assessed at 6 months. Enrolled patients were 63 years old on average, had a mean systolic blood pressure of 123 mm Hg, and a median left ventricular ejection fraction of 36%. About 16% of patients had a left ventricular ejection fraction of  50% or greater.

The data safety monitor board recommended terminating the trial early for benefit.

There were three main results:

  • The nearly 5-fold more frequent in-person visits led to far more patients in the high-intensity arm taking optimal doses of heart failure medications compared with those in the usual care arm.

  • Signs of congestion, such as weight, edema, jugular venous pressure, New York Heart Association class, and N-terminal pro–B-type natriuretic peptide level, all favored the high-intensity arm.

  • The primary endpoint occurred in 15.2% of patients in the high-intensity arm vs 23.1% in the usual care group (hazard ratio, 0.66; 95% CI, 0.50 - 0.86; P = .0021). Readmission for heart failure drove the benefit, but all-cause death was 16% lower and cardiovascular death was 26% lower in the high-intensity arm.

Adverse events occurred in 41% of the high-intensity arm vs 29% of the usual care arm, most commonly related to low blood pressure, hyperkalemia, and renal impairment. Serious and fatal adverse events did not differ significantly.


STRONG-HF is the strongest trial coming out of AHA. An 8–percentage point absolute risk reduction means that for every 12 patients treated with this protocol, a heart failure readmission or death is averted.

Taken as presented and published, these results should change practice. The most recent guideline statement from the European Society of Cardiology recommends a follow-up visit at 7 to 14 days. One visit. STRONG-HF included four visits in the first 6 weeks.

I don't know of any system doing this intense of a follow-up. In the question-and-answer session, Mebazaa said cardiologists performed these visits. That's not realistic in any health system I have seen.

The question is whether these results can be replicated with advanced practice professionals or pharmacists—perhaps aided by technology.

The authors, and just about everyone else I spoke with at AHA, attribute the better outcomes to maximal medical titration. Surely that's important, but STRONG-HF is an unblinded trial, and four visits in 6 weeks includes a lot of education, motivation, and caring. That should not be discounted. The counter to that caveat is that it doesn't matter how or why the results were better.

The limitations of this trial deserve mention. Most patients were enrolled from Russia and Africa. These are different health systems. How does this influence translation to North American and European systems?

For instance, in the subgroup analysis, the authors report no heterogeneity based on geography, but they included only Europe vs non-Europe categories. Russia was included as Europe. In the TOPCAT trial of spironolactone in patients with heart failure with a preserved ejection fraction, there was a dramatic amount of geographic heterogeneity in the results. I hope future papers address any TOPCAT-like effects.


If we use evidence to guide practice, health systems have their work cut out for them if they want to implement a STRONG-HF protocol. It will require a massive investment in people power and will not come at a low cost. Health leaders love to talk about better outcomes. Now it's time to bolster talk with action.

I look forward to watching how STRONG-HF influences care systems.

John Mandrola practices cardiac electrophysiology in Louisville, Kentucky, and is a writer and podcaster for Medscape. He espouses a conservative approach to medical practice. He participates in clinical research and writes often about the state of medical evidence. 

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