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HF Highlights at AHA 2020

CE / CME

Heart Failure at AHA 2020: My Take on Key Data

Physicians: Maximum of 0.25 AMA PRA Category 1 Credit™

Nurses: 0.25 Nursing contact hour

Released: December 09, 2020

Expiration: December 08, 2021

Javed Butler
Javed Butler, MD, MPH, MBA
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The 2020 American Heart Association Virtual Scientific Sessions (AHA 2020) were very interesting from a heart failure perspective. We saw new data from major clinical trials, including some secondary analyses from trials we have seen before. In this commentary, I briefly highlight what I consider to be the top studies in approved and investigational approaches in heart failure.

AFFIRM‑AHF
The data that were most exciting to me were from the AFFIRM‑AHF trial. This was an international, randomized, placebo-controlled, double-blind study designed to assess the impact of IV iron therapy on hospitalization and/or cardiovascular death in patients who were hospitalized for acute heart failure with reduced ejection fraction who also had iron deficiency (N = 1108).

Prior to AFFIRM-AHF, we had data from several trials examining functional capacity and quality-of-life data for patients with iron deficiency and heart failure with reduced ejection fraction. The results clearly demonstrated a benefit of IV iron replacement therapy in these patients. It makes them feel better, regardless of anemia (indeed, these outcomes insist that we should change our mindset about iron deficiency; it is a disease in and of itself whether anemia is present or not).

Although those studies were not designed to look at hospitalization risk, we saw secondary signals that IV iron also improved the risk for heart failure hospitalization. But those were smaller trials that were not powered to assess hospitalization outcomes. Moreover, the patient populations were stable, with chronic outpatient heart failure with reduced ejection fraction.

By contrast, the AFFIRM-AHF trial enrolled sicker patients who were hospitalized with new onset or chronic heart failure and iron deficiency regardless of anemia. And, of importance, it was powered for a 1‑year event rate.

The primary outcome of this trial was very exciting, showing a 26% relative risk reduction in heart failure hospitalization rate (RR: 0.74; P = .013). There was no significant impact on mortality alone. The primary composite endpoint analysis of total heart failure hospitalizations and cardiovascular death demonstrated a relative risk reduction of approximately 20% (RR: 0.79; P = .059).

I expect there will be a lot of debate about how to interpret that P value of .059. To me, the totality of evidence suggests that this is a real finding, because this is not the first trial. We know from previous trials that there is directional benefit of IV iron replacement, so I interpret this as a positive result.

In addition, the investigators performed further analysis of the primary composite endpoint in which they accounted for interruptions caused by the COVID-19 pandemic. They censored patients in each country by the date of the first report of COVID-19 in that region. And in that predefined, pre–COVID-19 analysis, the trial is positive with an HR of 0.79 and P value of .023.

Taken together, I think AFFIRM-AHF was the most practice‑modifying data to come out of this meeting. AFFIRM-AHF results highlight that, first and foremost, iron deficiency should be screened for in patients with heart failure with reduced ejection fraction who are hospitalized with decompensated heart failure. And in those with iron deficiency, with or without anemia, iron replacement (with IV ferric carboxymaltose) should be instituted to reduce the risk of recurrent hospitalizations.

INVESTED
INVESTED was another highly anticipated trial at AHA 2020. We have known for a long time that patients with cardiovascular risk factors have a higher risk of myocardial infarction, heart failure hospitalization, or decompensated heart failure after influenza infection. One can argue whether this is related to a propensity for more severe influenza disease or whether there are pathophysiologic contributors such as inflammation and stress, but regardless, the association is well known.

We also know that these older, sicker patients do not mount a robust immune response to the influenza vaccine and that their antibody responses may not be adequate for optimal protection. To this end, the randomized, double-blind INVESTED trial was designed to test low-dose vs high-dose influenza vaccination in patients with high-risk cardiovascular disease.

The trial was conducted over 3 influenza seasons, spanning from 2016-2019, and the primary endpoint was death or cardiopulmonary hospitalization within each influenza season. The trial was stopped early for futility, as there was no difference in the primary endpoint between the low-dose and high-dose groups (HR: 1.06; P = .21).

These results do not mean we should not give the influenza vaccine to patients with high-risk cardiovascular disease—the influenza vaccine is very important for our patients. INVESTED was a comparison of low-dose and high-dose vaccination, and there was no placebo arm. The important take-home message is that it does not matter whether we offer them low-dose or high-dose vaccination; whatever is available should be administered to these high-risk patients.

New Treatments: GALACTIC‑HF
The phase III GALACTIC‑HF trial is one of the largest trials ever conducted in patients with chronic heart failure with reduced ejection fraction. We have been waiting for results from this trial for a long time because we need new therapies to address the considerable residual risk in patients with chronic heart failure, and this study examined the first-in-class selective cardiac myosin activator omecamtiv mecarbil vs placebo in addition to standard-of-care therapy. There was a lot of interest in the novel mechanism of action of omecamtiv mecarbil. It is not another neurohormonal blocker and it makes a lot of sense to give a drug that increases cardiac contractility.

The results from GALACTIC-HF showed a modest, significant improvement with omecamtiv mecarbil in the primary composite endpoint of time to first heart failure event or cardiovascular death (HR: 0.92; P = .025). When analyzed individually, neither of the two components of this outcome  reached statistical significance. There was no effect of treatment on mortality (HR: 1.01; P = .86).

However, there did appear to be a mortality benefit in those with lower ejection fraction and we look forward to understanding these data further.

New Treatments: VICTORIA
Also at AHA 2020, we saw results from a secondary analysis of the phase III VICTORIA trial of the novel soluble guanylate cyclase stimulator vericiguat, where the story continues to evolve.

We saw previously that adding vericiguat to standard-of-care treatment in patients with worsening heart failure led to a 10% relative risk reduction and 4% absolute risk reduction for heart failure hospitalization or mortality. We subsequently learned that the treatment benefit correlated with levels of N-terminal pro–B-type natriuretic peptide (NT-proBNP), where patients with NT-proBNP < 8000 pg/mL had mortality and hospitalization benefits.

At AHA 2020, we learned that the proximity to hospitalization is also important for vericiguat treatment. In short, patients with the most recent hospitalization (< 3 months) remained at the highest risk for cardiovascular death or heart failure hospitalization whereas those who had never been hospitalized were at the lowest risk. Moreover, there was a continuous association between time from heart failure hospitalization and vericiguat treatment, which showed a trend toward greater benefit with longer duration since heart failure hospitalization.

This aligns with the previous reports on the correlation with NT-proBNP levels, further demonstrating that patients who are the most unstable and the most sick do not benefit as much from vericiguat treatment as those who are more stable.

EMPEROR‑Reduced
Finally, my colleagues and I presented results from a secondary analysis of the phase III EMPEROR‑Reduced trial showing quality-of-life benefit of the SGLT2 inhibitor empagliflozin in patients with heart failure with reduced ejection fraction. These data align with previous reports from the phase III DAPA‑HF trial of another SGLT2 inhibitor, dapagliflozin. The benefit was directionally and quantitatively similar between the 2 trials, demonstrating that the benefits of the SGLT2 inhibitor drug class are rapid and sustained and extend to improving overall quality of life.

Your Thoughts?
Which new heart failure data from AHA 2020 will have the greatest influence on your practice? Answer the polling question and join the conversation by posting a comment in the discussion section. And for more detailed data from these studies, download Capsule Summaries and reuse the slides in your own noncommercial presentations.

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