The combo drug sacubitril/valsartan was associated with early improvements in health status in a study of nearly 4,000 patients with heart failure with reduced ejection fraction (HFrEF).
The study, published in the November issue of JACC: Heart Failure, explored the efficacy of sacubitril/valsartan—an angiotensin-neprilysin inhibitor (ARNI)—in managing the health of patients with HFrEF and a left ventricular ejection fraction of 40% or less. Sacubitril/valsartan was first approved in the U.S. in 2015 following the results of the PARADIGM-HF trial, which found that patients who took the drug saw better survival and short-term health outcomes than those who took the ACE inhibitor enalapril.
In 2016, experts in both the U.S. and Europe penned guidelines recommending ARNIs as a first-line therapy or a replacement for ACE inhibitors or angiotensin receptor blockers (ARBs) in patients with HFrEF. Sacubitril/valsartan was the first medication in its new drug class.
“A limitation of the PARADIGM-HF trial was that patients’ health status was not assessed before the run-in phase, precluding an assessment of the early health status benefits of ARNI,” first author Yevgeniy Khariton, MD, a second-year CV fellow at Saint Luke’s Mid America Heart Institute, and colleagues wrote in JACC. “Moreover, the effectiveness of ARNI in patients’ health status in routine clinical practice is unknown.”
Khariton and his team assessed the health status of 3,918 HFrEF outpatients in the CHAMP-HF registry using the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ). ARNI therapy had been initiated in 508 patients, who were then matched 1:2 to 1,016 patients who weren’t taking an ARNI (no-ARNI).
Analyses revealed a greater mean improvement in KCCQ scores (KCCQ-OS) in ARNI patients compared to their no-ARNI counterparts—5.3 versus 2.5, respectively, over an average of 57 days. The proportion of ARNI versus no-ARNI groups with more than 10-point (large) and 20-point (very large) improvements in their KCCQ-OS were 32.7% versus 26.9%, respectively, and 20.5% versus 12.1%, respectively, consistent with numbers needed to treat of 18 and 12.
“This study captures the real-life health status benefits that a patient initiated on sacubitril/valsartan therapy might expect to experience,” Oluwakemi Okunade, MD, MPH, of Archway Health in Boston, wrote in a related editorial. “It is worth noting that the actual differences in patient-reported health status found between the ARNI group and the comparison group were modest. Also, in both the ARNI and the comparison group, more than one-half of the study population had a small improvement or no improvement or reported a deterioration in their KCCQ score.”
So, how much do patient-reported outcomes matter? Okunade said that, in this case, it’s easy to argue that they’re somewhat insignificant given the overwhelming evidence of benefit associated with ARNIs. But she also said that’s a “paternalistic view that places the conventional preference of the medical profession over those of the individual patient.”
While some patients care more about prolonging their life by a certain number of years, others are more focused on improving the quality of what life they have left, Okunade wrote. So it’s possible that patients who reported health status improvements with ARNI therapy might value additional years more than those who didn’t report improvements.
Okunade and the study’s authors both recognized a need for further study on the subject.
“If patients and their preferences are to be at the center of healthcare delivery, patient-reported quality of life data must be measured and assessed with the same consistency as mortality and cardiovascular endpoints,” the editorialist wrote. “The most important step is shifting clinicians’ perception of collecting standardized patient-reported health outcomes as a burdensome chore to recognizing it as a valuable tool that enhances patient-clinician interactions.”