PIONEER-HF: Favorable Results for Sacubitril-Valsartan in Acute Decompensated HF

Acute decompensated heart failure is a common infection, accounting for more than 1 million hospitalizations in the United States annually, and while prevalent, treatment has not been altered in several decades. Additionally, there is a lack of guidance on how to care for patients who are hospitalized with heart failure.

The results from the PIONEER-HF study, presented today in a late breaker session at the American Heart Association Scientific Session in Chicago, Illinois, demonstrate that when compared with enalapril, administration of sacubitril—valsartan therapy over 8 weeks led to greater reduction in N-terminal pro–B-type natriuretic peptide (NT-proBNP), and reduced re-hospitalization for heart failure, and was well tolerated.

The PARADIGM-Heart Failure trial previously compared sacubitril—valsartan and enalapril and demonstrated showed that administration of sacubitril–valsartan led to a reduction in cardiovascular deaths and hospitalizations for heart failure but excluded patients in acute heart failure.

According to Eric Velazquez, MD, Chief of Cardiovascular Medicine at Yale University and principal investigator of the PIONEER-HF study, the lack of evidence in this population became the basis for the PIONEER-HF study.

“We had an evidence gap; we had no data,” Dr. Velazquez told MD Magazine®, “We had a very limited armamentarium for care in the acute heart failure setting and we had a new therapy that had never been tested in the heart failure hospitalized setting. So, we wanted to see if we could make a difference by implementing that drug in the hospital.”

The PIONEER trial enrolled 881 patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure at 129 sites in the United States. Following hemodynamic stabilization, the patients were randomized to receive either sacubitril—valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or enalapril (target dose, 10 mg twice daily).

The primary efficacy outcome of the study was a change NT-proBNP, which has been linked to prognosis and outcomes in patients with heart failure, through week 4 and 8. The investigators also looked at safety outcomes including worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema. Finally, the investigators looked at rates in exploratory analyses of clinical endpoints including rate of death, heart failure hospitalization, implantation of left ventricular assist device or listing for transplantation.

“We know that this drug works to reduce this marker of risk and it works very quickly and is persistent and sustained over 8 weeks,” Dr. Velazquez said (see video).

In total 440 participants were assigned to receive sacubitril—valsartan and 441 were assigned to receive enalapril.

According to the results, the time-averaged reduction in the NT-proBNP concentration was significantly greater in the sacubitril—valsartan group with a “ratio of the geometric mean of values obtained at weeks 4 and 8 to the baseline value was 0.53 in the sacubitril–valsartan group as compared with 0.75 in the enalapril group (percent change, −46.7% vs. −25.3%; ratio of change with sacubitril–valsartan vs. enalapril, 0.71; 95% confidence interval [CI], 0.63 to 0.81; P<0.001).”

Additionally, the rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema did not differ significantly between the two groups. On blinded adjudication, there was 1 confirmed angioedema event in a white patient in the sacubitril—valsartan group and there were 6 angioedema events in all black patients in the enalapril group.

“And so overall what I believe this this means it really marks a new day for acute heart fair patients…in the acute hospital setting for patients who've been stabilized, this view of valsartan, leads to better outcomes. We have the long-term data in chronic patients from PARADIGM that it also reduces outcomes so put together it really does say that I think the emerging standard will likely be that for patients with acute heart failure, once you've congested them and stabilized, then sacubitril—valsartan will lead to a benefit,” Dr. Velazquez concluded.

The study, “Angiotensin Receptor-Neprilysin Inhibition in Patients Hospitalized With Acute Decompensated Heart Failure: Primary Results of the PIONEER-HF Randomized Controlled Trial” was presented on November 11, 2018, by Eric Velazquez, MD, and was simultaneously published in an article in the New England Journal of Medicine.