Trending Clinical Topic: Sacubitril/Valsartan

Ryan Syrek


May 28, 2021

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Results of the PARADISE-MI trial, which compared sacubitril/valsartan vs ramipril, led off the late-breaking clinical trial session at the American College of Cardiology (ACC) 2021 Scientific Session (see Infographic below). The disappointing findings, along with reactions from experts, resulted in this week's top trending clinical topic.

In the trial, which included more than 5600 patients who had a myocardial infarction (MI) but had no history of heart failure, treatment with sacubitril/valsartan came close to showing efficacy for preventing cardiovascular death and heart failure events. Although it fell short of producing a significant benefit, the study's author, Marc A. Pfeffer, MD, says that the medication proved to be "as well-tolerated and as safe" as ramipril and believes that it should lead to "lower barriers" to its broader use.

Sacubitril/valsartan has been approved for heart failure with reduced ejection fraction since 2015, after the results of the PARADIGM HF trial. Interest in the medication increased earlier this year when the US Food and Drug Administration (FDA) approved a groundbreaking expanded indication for sacubitril/valsartan, making it the first drug in the United States indicated for chronic heart failure not specifically characterized by ejection fraction. That expansion provided physicians a good deal of discretion in prescribing the medication.

In discussing the PARADISE-MI results, Pfeffer explained that although sacubitril/valsartan did not reach the 15% reduction needed to declare significance, the medication performed well in other analyses. "We probed, and every analysis we conducted favored sacubitril/valsartan numerically," Pfeffer said. "We didn't just look at the first event but the total burden of heart disease, and we looked at recurrent events. Then it became quite clear that you'd rather be on sacubitril/valsartan."

However, other experts say the results give them pause when considering the treatment as an option. In response to the PARADISE-MI findings, John Mandrola, MD, explained that the medication has now missed statistical significance in two of three major clinical outcomes trials, as it also missed the benchmark in the PARAGON-HF trial. He also pointed out that "sacubitril/valsartan costs vastly more than generic ramipril. Cost matters because money spent on one thing means less is available for others. Think disparities in care."

Navigating prior authorization and out-of-pocket costs for drugs like these has proven challenging for many physicians, specifically for patients who have heart failure with reduced ejection fraction. Although sacubitril/valsartan was eligible for patent challenges in July 2019, a generic equivalent is still not likely until 2027. Still, despite the cost concerns and disappointing findings presented at the ACC session, interest in sacubitril/valsartan remains high, as evident by its becoming this week's top trending clinical topic.

Read more about MI treatment.


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